Efficient block processing of long duration biotelemetric brain data for health care monitoring
DOE Office of Scientific and Technical Information (OSTI.GOV)
Soumya, I.; Zia Ur Rahman, M., E-mail: mdzr-5@ieee.org; Rama Koti Reddy, D. V.
In real time clinical environment, the brain signals which doctor need to analyze are usually very long. Such a scenario can be made simple by partitioning the input signal into several blocks and applying signal conditioning. This paper presents various block based adaptive filter structures for obtaining high resolution electroencephalogram (EEG) signals, which estimate the deterministic components of the EEG signal by removing noise. To process these long duration signals, we propose Time domain Block Least Mean Square (TDBLMS) algorithm for brain signal enhancement. In order to improve filtering capability, we introduce normalization in the weight update recursion of TDBLMS,more » which results TD-B-normalized-least mean square (LMS). To increase accuracy and resolution in the proposed noise cancelers, we implement the time domain cancelers in frequency domain which results frequency domain TDBLMS and FD-B-Normalized-LMS. Finally, we have applied these algorithms on real EEG signals obtained from human using Emotive Epoc EEG recorder and compared their performance with the conventional LMS algorithm. The results show that the performance of the block based algorithms is superior to the LMS counter-parts in terms of signal to noise ratio, convergence rate, excess mean square error, misadjustment, and coherence.« less
Real Time Implementation of an LPC Algorithm. Speech Signal Processing Research at CHI
1975-05-01
SIGNAL PROCESSING HARDWARE 2-1 2.1 INTRODUCTION 2-1 2.2 TWO- CHANNEL AUDIO SIGNAL SYSTEM 2-2 2.3 MULTI- CHANNEL AUDIO SIGNAL SYSTEM 2-5 2.3.1... Channel Audio Signal System 2-30 I ii kv^i^ünt«.jfc*. ji .„* ,:-v*. ’.ii. *.. ...... — ■ -,,.,-c-» —ipponp ■^ TOHaBWgBpwiBWgPlpaiPWgW v.«.wN...Messages .... 1-55 1-13. Lost or Out of Order Message 1-56 2-1. Block Diagram of Two- Channel Audio Signal System . . 2-3 2-2. Block Diagram of Audio
Diagnosis diagrams for passing signals on an automatic block signaling railway section
NASA Astrophysics Data System (ADS)
Spunei, E.; Piroi, I.; Chioncel, C. P.; Piroi, F.
2018-01-01
This work presents a diagnosis method for railway traffic security installations. More specifically, the authors present a series of diagnosis charts for passing signals on a railway block equipped with an automatic block signaling installation. These charts are based on the exploitation electric schemes, and are subsequently used to develop a diagnosis software package. The thus developed software package contributes substantially to a reduction of failure detection and remedy for these types of installation faults. The use of the software package eliminates making wrong decisions in the fault detection process, decisions that may result in longer remedy times and, sometimes, to railway traffic events.
Error Propagation in a System Model
NASA Technical Reports Server (NTRS)
Schloegel, Kirk (Inventor); Bhatt, Devesh (Inventor); Oglesby, David V. (Inventor); Madl, Gabor (Inventor)
2015-01-01
Embodiments of the present subject matter can enable the analysis of signal value errors for system models. In an example, signal value errors can be propagated through the functional blocks of a system model to analyze possible effects as the signal value errors impact incident functional blocks. This propagation of the errors can be applicable to many models of computation including avionics models, synchronous data flow, and Kahn process networks.
Multi-DSP and FPGA based Multi-channel Direct IF/RF Digital receiver for atmospheric radar
NASA Astrophysics Data System (ADS)
Yasodha, Polisetti; Jayaraman, Achuthan; Kamaraj, Pandian; Durga rao, Meka; Thriveni, A.
2016-07-01
Modern phased array radars depend highly on digital signal processing (DSP) to extract the echo signal information and to accomplish reliability along with programmability and flexibility. The advent of ASIC technology has made various digital signal processing steps to be realized in one DSP chip, which can be programmed as per the application and can handle high data rates, to be used in the radar receiver to process the received signal. Further, recent days field programmable gate array (FPGA) chips, which can be re-programmed, also present an opportunity to utilize them to process the radar signal. A multi-channel direct IF/RF digital receiver (MCDRx) is developed at NARL, taking the advantage of high speed ADCs and high performance DSP chips/FPGAs, to be used for atmospheric radars working in HF/VHF bands. Multiple channels facilitate the radar t be operated in multi-receiver modes and also to obtain the wind vector with improved time resolution, without switching the antenna beam. MCDRx has six channels, implemented on a custom built digital board, which is realized using six numbers of ADCs for simultaneous processing of the six input signals, Xilinx vertex5 FPGA and Spartan6 FPGA, and two ADSPTS201 DSP chips, each of which performs one phase of processing. MCDRx unit interfaces with the data storage/display computer via two gigabit ethernet (GbE) links. One of the six channels is used for Doppler beam swinging (DBS) mode and the other five channels are used for multi-receiver mode operations, dedicatedly. Each channel has (i) ADC block, to digitize RF/IF signal, (ii) DDC block for digital down conversion of the digitized signal, (iii) decoding block to decode the phase coded signal, and (iv) coherent integration block for integrating the data preserving phase intact. ADC block consists of Analog devices make AD9467 16-bit ADCs, to digitize the input signal at 80 MSPS. The output of ADC is centered around (80 MHz - input frequency). The digitized data is fed to DDC block, which down converts the data to base-band. The DDC block has NCO, mixer and two chains of Bessel filters (fifth order cascaded integration comb filter, two FIR filters, two half band filters and programmable FIR filters) for in-phase (I) and Quadrature phase (Q) channels. The NCO has 32 bits and is set to match the output frequency of ADC. Further, DDC down samples (decimation) the data and reduces the data rate to 16 MSPS. This data is further decimated and the data rate is reduced down to 4/2/1/0.5/0.25/0.125/0.0625 MSPS for baud lengths 0.25/0.5/1/2/4/8/16 μs respectively. The down sampled data is then fed to decoding block, which performs cross correlation to achieve pulse compression of the binary-phase coded data to obtain better range resolution with maximum possible height coverage. This step improves the signal power by a factor equal to the length of the code. Coherent integration block integrates the decoded data coherently for successive pulses, which improves the signal to noise ratio and reduces the data volume. DDC, decoding and coherent integration blocks are implemented in Xilinx vertex5 FPGA. Till this point, function of all six channels is same for DBS mode and multi-receiver modes. Data from vertex5 FPGA is transferred to PC via GbE-1 interface for multi-modes or to two Analog devices make ADSP-TS201 DSP chips (A and B), via link port for DBS mode. ADSP-TS201 chips perform the normalization, DC removal, windowing, FFT computation and spectral averaging on the data, which is transferred to storage/display PC via GbE-2 interface for real-time data display and data storing. Physical layer of GbE interface is implemented in an external chip (Marvel 88E1111) and MAC layer is implemented internal to vertex5 FPGA. The MCDRx has total 4 GB of DDR2 memory for data storage. Spartan6 FPGA is used for generating timing signals, required for basic operation of the radar and testing of the MCDRx.
Synthetic aperture radar signal data compression using block adaptive quantization
NASA Technical Reports Server (NTRS)
Kuduvalli, Gopinath; Dutkiewicz, Melanie; Cumming, Ian
1994-01-01
This paper describes the design and testing of an on-board SAR signal data compression algorithm for ESA's ENVISAT satellite. The Block Adaptive Quantization (BAQ) algorithm was selected, and optimized for the various operational modes of the ASAR instrument. A flexible BAQ scheme was developed which allows a selection of compression ratio/image quality trade-offs. Test results show the high quality of the SAR images processed from the reconstructed signal data, and the feasibility of on-board implementation using a single ASIC.
Miller, Jeff; Sproesser, Gudrun; Ulrich, Rolf
2008-07-01
In two experiments, we used response signals (RSs) to control processing time and trace out speed--accuracy trade-off(SAT) functions in a difficult perceptual discrimination task. Each experiment compared performance in blocks of trials with constant and, hence, temporally predictable RS lags against performance in blocks with variable, unpredictable RS lags. In both experiments, essentially equivalent SAT functions were observed with constant and variable RS lags. We conclude that there is little effect of advance preparation for a given processing time, suggesting that the discrimination mechanisms underlying SAT functions are driven solely by bottom-up information processing in perceptual discrimination tasks.
49 CFR 236.824 - System, automatic block signal.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 4 2010-10-01 2010-10-01 false System, automatic block signal. 236.824 Section... § 236.824 System, automatic block signal. A block signal system wherein the use of each block is governed by an automatic block signal, cab signal, or both. ...
Yanochko, Gina M.; Yool, Andrea J.
2004-01-01
Drosophila Big Brain (BIB) is a transmembrane protein encoded by the neurogenic gene big brain (bib), which is important for early development of the fly nervous system. BIB expressed in Xenopus oocytes is a monovalent cation channel modulated by tyrosine kinase signaling. Results here demonstrate that the BIB conductance shows voltage- and dose-dependent block by extracellular divalent cations Ca2+ and Ba2+ but not by Mg2+ in wild-type channels. Site-directed mutagenesis of negatively charged glutamate (Glu274) and aspartate (Asp253) residues had no effect on divalent cation block. However, mutation of a conserved glutamate at position 71 (Glu71) in the first transmembrane domain (M1) altered channel properties. Mutation of Glu71 to Asp introduced a new sensitivity to block by extracellular Mg2+; substitutions with asparagine or glutamine decreased whole-cell conductance; and substitution with lysine compromised plasma membrane expression. Block by divalent cations is important in other ion channels for voltage-dependent function, enhanced signal resolution, and feedback regulation. Our data show that the wild-type BIB conductance is attenuated by external Ca2+, suggesting that endogenous divalent cation block might be relevant for enhancing signal resolution or voltage dependence for the native signaling process in neuronal cell fate determination. PMID:14990474
49 CFR 236.827 - System, block signal.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 4 2010-10-01 2010-10-01 false System, block signal. 236.827 Section 236.827... System, block signal. A method of governing the movement of trains into or within one or more blocks by block signals or cab signals. ...
Evaluation of hardware costs of implementing PSK signal detection circuit based on "system on chip"
NASA Astrophysics Data System (ADS)
Sokolovskiy, A. V.; Dmitriev, D. D.; Veisov, E. A.; Gladyshev, A. B.
2018-05-01
The article deals with the choice of the architecture of digital signal processing units for implementing the PSK signal detection scheme. As an assessment of the effectiveness of architectures, the required number of shift registers and computational processes are used when implementing the "system on a chip" on the chip. A statistical estimation of the normalized code sequence offset in the signal synchronization scheme for various hardware block architectures is used.
Genetics Home Reference: Shprintzen-Goldberg syndrome
... the transforming growth factor beta (TGF-β) signaling pathway. The TGF-β pathway regulates many processes, including cell growth and division ( ... apoptosis ). By attaching to certain proteins in the pathway, the SKI protein blocks TGF-β signaling. The ...
Sun, Jiedi; Yu, Yang; Wen, Jiangtao
2017-01-01
Remote monitoring of bearing conditions, using wireless sensor network (WSN), is a developing trend in the industrial field. In complicated industrial environments, WSN face three main constraints: low energy, less memory, and low operational capability. Conventional data-compression methods, which concentrate on data compression only, cannot overcome these limitations. Aiming at these problems, this paper proposed a compressed data acquisition and reconstruction scheme based on Compressed Sensing (CS) which is a novel signal-processing technique and applied it for bearing conditions monitoring via WSN. The compressed data acquisition is realized by projection transformation and can greatly reduce the data volume, which needs the nodes to process and transmit. The reconstruction of original signals is achieved in the host computer by complicated algorithms. The bearing vibration signals not only exhibit the sparsity property, but also have specific structures. This paper introduced the block sparse Bayesian learning (BSBL) algorithm which works by utilizing the block property and inherent structures of signals to reconstruct CS sparsity coefficients of transform domains and further recover the original signals. By using the BSBL, CS reconstruction can be improved remarkably. Experiments and analyses showed that BSBL method has good performance and is suitable for practical bearing-condition monitoring. PMID:28635623
49 CFR 236.824 - System, automatic block signal.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 49 Transportation 4 2011-10-01 2011-10-01 false System, automatic block signal. 236.824 Section..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.824 System, automatic block signal. A block signal system wherein the use of each block is...
49 CFR 236.824 - System, automatic block signal.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 49 Transportation 4 2014-10-01 2014-10-01 false System, automatic block signal. 236.824 Section..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.824 System, automatic block signal. A block signal system wherein the use of each block is...
49 CFR 236.824 - System, automatic block signal.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 49 Transportation 4 2013-10-01 2013-10-01 false System, automatic block signal. 236.824 Section..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.824 System, automatic block signal. A block signal system wherein the use of each block is...
1977-12-30
ACOUSTO - OPTIC INTERACTION IN SURFACE ACOUSTIC WAVES AND ITS APP--ETC(U) DEC 77 0 SCHUMER, P DAS NOOOIJ -75-C-0772 NCLASSIFIED MA-ONR-30 Nt.EE E’h...CHART NAT*NAL BUREAU OF STANDARDS 1-63- ACOUSTO - OPTIC INTERACTION IN SURFACE ACOUSTIC WAVES AND ITS APPLICATION TO REAL TIME SIGNAL PROCESSING By 00 D... Acousto - optics , Integrated optics, Optical Signal Processing. 20. AbSKTRACT (Continue an reverse side it neceary and idewnt& by block mum ber) The
Investigation of charge coupled device correlation techniques
NASA Technical Reports Server (NTRS)
Lampe, D. R.; Lin, H. C.; Shutt, T. J.
1978-01-01
Analog Charge Transfer Devices (CTD's) offer unique advantages to signal processing systems, which often have large development costs, making it desirable to define those devices which can be developed for general system's use. Such devices are best identified and developed early to give system's designers some interchangeable subsystem blocks, not requiring additional individual development for each new signal processing system. The objective of this work is to describe a discrete analog signal processing device with a reasonably broad system use and to implement its design, fabrication, and testing.
Kavuri, Shyam M.; Geserick, Peter; Berg, Daniela; Dimitrova, Diana Panayotova; Feoktistova, Maria; Siegmund, Daniela; Gollnick, Harald; Neumann, Manfred; Wajant, Harald; Leverkus, Martin
2011-01-01
Death receptors (DRs) induce apoptosis but also stimulate proinflammatory “non-apoptotic” signaling (e.g. NF-κB and mitogen-activated protein kinase (MAPK) activation) and inhibit distinct steps of DR-activated maturation of procaspase-8. To examine whether isoforms of cellular FLIP (cFLIP) or its cleavage products differentially regulate DR signaling, we established HaCaT cells expressing cFLIPS, cFLIPL, or mutants of cFLIPL (cFLIPD376N and cFLIPp43). cFLIP variants blocked TRAIL- and CD95L-induced apoptosis, but the cleavage pattern of caspase-8 in the death inducing signaling complex was different: cFLIPL induced processing of caspase-8 to the p43/41 fragments irrespective of cFLIP cleavage. cFLIPS or cFLIPp43 blocked procaspase-8 cleavage. Analyzing non-apoptotic signaling pathways, we found that TRAIL and CD95L activate JNK and p38 within 15 min. cFLIP variants and different caspase inhibitors blocked late death ligand-induced JNK or p38 MAPK activation suggesting that these responses are secondary to cell death. cFLIP isoforms/mutants also blocked death ligand-mediated gene induction of CXCL-8 (IL-8). Knockdown of caspase-8 fully suppressed apoptotic and non-apoptotic signaling. Knockdown of cFLIP isoforms in primary human keratinocytes enhanced CD95L- and TRAIL-induced NF-κB activation, and JNK and p38 activation, underscoring the regulatory role of cFLIP for these DR-mediated signals. Whereas the presence of caspase-8 is critical for apoptotic and non-apoptotic signaling, cFLIP isoforms are potent inhibitors of TRAIL- and CD95L-induced apoptosis, NF-κB activation, and the late JNK and p38 MAPK activation. cFLIP-mediated inhibition of CD95 and TRAIL DR could be of crucial importance during keratinocyte skin carcinogenesis and for the activation of innate and/or adaptive immune responses triggered by DR activation in the skin. PMID:21454681
Vanin, Evgeny; Jacobsen, Gunnar
2010-03-01
The Bit-Error-Ratio (BER) floor caused by the laser phase noise in the optical fiber communication system with differential quadrature phase shift keying (DQPSK) and coherent detection followed by digital signal processing (DSP) is analytically evaluated. An in-phase and quadrature (I&Q) receiver with a carrier phase recovery using DSP is considered. The carrier phase recovery is based on a phase estimation of a finite sum (block) of the signal samples raised to the power of four and the phase unwrapping at transitions between blocks. It is demonstrated that errors generated at block transitions cause the dominating contribution to the system BER floor when the impact of the additive noise is negligibly small in comparison with the effect of the laser phase noise. Even the BER floor in the case when the phase unwrapping is omitted is analytically derived and applied to emphasize the crucial importance of this signal processing operation. The analytical results are verified by full Monte Carlo simulations. The BER for another type of DQPSK receiver operation, which is based on differential phase detection, is also obtained in the analytical form using the principle of conditional probability. The principle of conditional probability is justified in the case of differential phase detection due to statistical independency of the laser phase noise induced signal phase error and the additive noise contributions. Based on the achieved analytical results the laser linewidth tolerance is calculated for different system cases.
NASA Technical Reports Server (NTRS)
Mojarradi, M. M.; Blaes, B.; Kolawa, E. A.; Blalock, B. J.; Li, H. W.; Buck, K.; Houge, D.
2001-01-01
To build the sensor intensive system-on-a-chip for the next generation spacecrafts for deep space, Center for Integration of Space Microsystems at JPL (CISM) takes advantage of the lower power rating and inherent radiation resistance of Silicon on Insulator technology (SOI). We are developing a suite of mixed-voltage and mixed-signal building blocks in Honeywell's SOI process that can enable the rapid integration of the next generation avionics systems with lower power rating, higher reliability, longer life, and enhanced radiation tolerance for spacecrafts such as the Europa Orbiter and Europa Lander. The mixed-voltage building blocks are predominantly for design of adaptive power management systems. Their design centers around an LDMOS structure that is being developed by Honeywell, Boeing Corp, and the University of Idaho. The mixed-signal building blocks are designed to meet the low power, extreme radiation requirement of deep space applications. These building blocks are predominantly used to interface analog sensors to the digital CPU of the next generation avionics system on a chip. Additional information is contained in the original extended abstract.
NASA Technical Reports Server (NTRS)
Kumar, P.; Lin, F. Y.; Vaishampayan, V.; Farvardin, N.
1986-01-01
A complete documentation of the software developed in the Communication and Signal Processing Laboratory (CSPL) during the period of July 1985 to March 1986 is provided. Utility programs and subroutines that were developed for a user-friendly image and speech processing environment are described. Additional programs for data compression of image and speech type signals are included. Also, programs for the zero-memory and block transform quantization in the presence of channel noise are described. Finally, several routines for simulating the perfromance of image compression algorithms are included.
Full-Circle Resolver-to-Linear-Analog Converter
NASA Technical Reports Server (NTRS)
Alhorn, Dean C.; Smith, Dennis A.; Howard, David E.
2005-01-01
A circuit generates sinusoidal excitation signals for a shaft-angle resolver and, like the arctangent circuit described in the preceding article, generates an analog voltage proportional to the shaft angle. The disadvantages of the circuit described in the preceding article arise from the fact that it must be made from precise analog subcircuits, including a functional block capable of implementing some trigonometric identities; this circuitry tends to be expensive, sensitive to noise, and susceptible to errors caused by temperature-induced drifts and imprecise matching of gains and phases. These disadvantages are overcome by the design of the present circuit. The present circuit (see figure) includes an excitation circuit, which generates signals Ksin(Omega(t)) and Kcos(Omega(t)) [where K is an amplitude, Omega denotes 2(pi)x a carrier frequency (the design value of which is 10 kHz), and t denotes time]. These signals are applied to the excitation terminals of a shaft-angle resolver, causing the resolver to put out signals C sin(Omega(t)-Theta) and C cos(Omega(t)-Theta). The cosine excitation signal and the cosine resolver output signal are processed through inverting comparator circuits, which are configured to function as inverting squarers, to obtain logic-level or square-wave signals .-LL[cos(Omega(t)] and -LL[cos(Omega(t)-Theta)], respectively. These signals are fed as inputs to a block containing digital logic circuits that effectively measure the phase difference (which equals Theta between the two logic-level signals). The output of this block is a pulse-width-modulated signal, PWM(Theta), the time-averaged value of which ranges from 0 to 5 VDC as Theta ranges from .180 to +180deg. PWM(Theta) is fed to a block of amplifying and level-shifting circuitry, which converts the input PWM waveform to an output waveform that switches between precise reference voltage levels of +10 and -10 V. This waveform is processed by a two-pole, low-pass filter, which removes the carrier-frequency component. The final output signal is a DC potential, proportional to Theta that ranges continuously from -10 V at Theta = -180deg to +10 V at Theta = +180deg..
NASA Astrophysics Data System (ADS)
Azarpour, Masoumeh; Enzner, Gerald
2017-12-01
Binaural noise reduction, with applications for instance in hearing aids, has been a very significant challenge. This task relates to the optimal utilization of the available microphone signals for the estimation of the ambient noise characteristics and for the optimal filtering algorithm to separate the desired speech from the noise. The additional requirements of low computational complexity and low latency further complicate the design. A particular challenge results from the desired reconstruction of binaural speech input with spatial cue preservation. The latter essentially diminishes the utility of multiple-input/single-output filter-and-sum techniques such as beamforming. In this paper, we propose a comprehensive and effective signal processing configuration with which most of the aforementioned criteria can be met suitably. This relates especially to the requirement of efficient online adaptive processing for noise estimation and optimal filtering while preserving the binaural cues. Regarding noise estimation, we consider three different architectures: interaural (ITF), cross-relation (CR), and principal-component (PCA) target blocking. An objective comparison with two other noise PSD estimation algorithms demonstrates the superiority of the blocking-based noise estimators, especially the CR-based and ITF-based blocking architectures. Moreover, we present a new noise reduction filter based on minimum mean-square error (MMSE), which belongs to the class of common gain filters, hence being rigorous in terms of spatial cue preservation but also efficient and competitive for the acoustic noise reduction task. A formal real-time subjective listening test procedure is also developed in this paper. The proposed listening test enables a real-time assessment of the proposed computationally efficient noise reduction algorithms in a realistic acoustic environment, e.g., considering time-varying room impulse responses and the Lombard effect. The listening test outcome reveals that the signals processed by the blocking-based algorithms are significantly preferred over the noisy signal in terms of instantaneous noise attenuation. Furthermore, the listening test data analysis confirms the conclusions drawn based on the objective evaluation.
49 CFR 236.804 - Signal, block.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 49 Transportation 4 2011-10-01 2011-10-01 false Signal, block. 236.804 Section 236.804..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.804 Signal, block. A roadway signal operated either automatically or manually at the entrance to a block. ...
49 CFR 236.804 - Signal, block.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 49 Transportation 4 2014-10-01 2014-10-01 false Signal, block. 236.804 Section 236.804..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.804 Signal, block. A roadway signal operated either automatically or manually at the entrance to a block. ...
49 CFR 236.804 - Signal, block.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 49 Transportation 4 2013-10-01 2013-10-01 false Signal, block. 236.804 Section 236.804..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.804 Signal, block. A roadway signal operated either automatically or manually at the entrance to a block. ...
49 CFR 236.804 - Signal, block.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 49 Transportation 4 2012-10-01 2012-10-01 false Signal, block. 236.804 Section 236.804..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.804 Signal, block. A roadway signal operated either automatically or manually at the entrance to a block. ...
Compact conscious animal positron emission tomography scanner
Schyler, David J.; O'Connor, Paul; Woody, Craig; Junnarkar, Sachin Shrirang; Radeka, Veljko; Vaska, Paul; Pratte, Jean-Francois; Volkow, Nora
2006-10-24
A method of serially transferring annihilation information in a compact positron emission tomography (PET) scanner includes generating a time signal for an event, generating an address signal representing a detecting channel, generating a detector channel signal including the time and address signals, and generating a composite signal including the channel signal and similarly generated signals. The composite signal includes events from detectors in a block and is serially output. An apparatus that serially transfers annihilation information from a block includes time signal generators for detectors in a block and an address and channel signal generator. The PET scanner includes a ring tomograph that mounts onto a portion of an animal, which includes opposing block pairs. Each of the blocks in a block pair includes a scintillator layer, detection array, front-end array, and a serial encoder. The serial encoder includes time signal generators and an address signal and channel signal generator.
Duque, Julie; Labruna, Ludovica; Cazares, Christian; Ivry, Richard B.
2014-01-01
Motor behavior requires selecting between potential actions. The role of inhibition in response selection has frequently been examined in tasks in which participants are engaged in some advance preparation prior to the presentation of an imperative signal. Under such conditions, inhibition could be related to processes associated with response selection, or to more general inhibitory processes that are engaged in high states of anticipation. In Experiment 1, we manipulated the degree of anticipatory preparation. Participants performed a choice reaction time task that required choosing between a movement of the left or right index finger, and used transcranial magnetic stimulation (TMS) to elicit motor evoked potentials (MEPs) in the left hand agonist. In high anticipation blocks, a non-informative cue (e.g., fixation marker) preceded the imperative; in low anticipation blocks, there was no cue and participants were required to divide their attention between two tasks to further reduce anticipation. MEPs were substantially reduced before the imperative signal in high anticipation blocks. In contrast, in low anticipation blocks, MEPs remained unchanged before the imperative signal but showed a marked suppression right after the onset of the imperative. This effect occurred regardless of whether the imperative had signaled a left or right hand response. After this initial inhibition, left MEPs increased when the left hand was selected and remained suppressed when the right hand was selected. We obtained similar results in Experiment 2 except that the persistent left MEP suppression when the left hand was not selected was attenuated when the alternative response involved a non-homologous effector (right foot). These results indicate that, even in the absence of an anticipatory period, inhibitory mechanisms are engaged during response selection, possibly to prevent the occurrence of premature and inappropriate responses during a competitive selection process. PMID:25128431
49 CFR 236.804 - Signal, block.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 4 2010-10-01 2010-10-01 false Signal, block. 236.804 Section 236.804 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Signal, block. A roadway signal operated either automatically or manually at the entrance to a block. ...
Konig, Stéphane; Béguet, Anne; Bader, Charles R; Bernheim, Laurent
2006-08-01
In human myoblasts triggered to differentiate, a hyperpolarization, resulting from K+ channel (Kir2.1) activation, allows the generation of an intracellular Ca2+ signal. This signal induces an increase in expression/activity of two key transcription factors of the differentiation process, myogenin and MEF2. Blocking hyperpolarization inhibits myoblast differentiation. The link between hyperpolarization-induced Ca2+ signals and the four main regulatory pathways involved in myoblast differentiation was the object of this study. Of the calcineurin, p38-MAPK, PI3K and CaMK pathways, only the calcineurin pathway was inhibited when Kir2.1-linked hyperpolarization was blocked. The CaMK pathway, although Ca2+ dependent, is unaffected by changes in membrane potential or block of Kir2.1 channels. Concerning the p38-MAPK and PI3K pathways, their activity is present already in proliferating myoblasts and they are unaffected by hyperpolarization or Kir2.1 channel block. We conclude that the Kir2.1-induced hyperpolarization triggers human myoblast differentiation via the activation of the calcineurin pathway, which, in turn, induces expression/activity of myogenin and MEF2.
Software Defined Radio with Parallelized Software Architecture
NASA Technical Reports Server (NTRS)
Heckler, Greg
2013-01-01
This software implements software-defined radio procession over multicore, multi-CPU systems in a way that maximizes the use of CPU resources in the system. The software treats each processing step in either a communications or navigation modulator or demodulator system as an independent, threaded block. Each threaded block is defined with a programmable number of input or output buffers; these buffers are implemented using POSIX pipes. In addition, each threaded block is assigned a unique thread upon block installation. A modulator or demodulator system is built by assembly of the threaded blocks into a flow graph, which assembles the processing blocks to accomplish the desired signal processing. This software architecture allows the software to scale effortlessly between single CPU/single-core computers or multi-CPU/multi-core computers without recompilation. NASA spaceflight and ground communications systems currently rely exclusively on ASICs or FPGAs. This software allows low- and medium-bandwidth (100 bps to approx.50 Mbps) software defined radios to be designed and implemented solely in C/C++ software, while lowering development costs and facilitating reuse and extensibility.
Software Defined Radio with Parallelized Software Architecture
NASA Technical Reports Server (NTRS)
Heckler, Greg
2013-01-01
This software implements software-defined radio procession over multi-core, multi-CPU systems in a way that maximizes the use of CPU resources in the system. The software treats each processing step in either a communications or navigation modulator or demodulator system as an independent, threaded block. Each threaded block is defined with a programmable number of input or output buffers; these buffers are implemented using POSIX pipes. In addition, each threaded block is assigned a unique thread upon block installation. A modulator or demodulator system is built by assembly of the threaded blocks into a flow graph, which assembles the processing blocks to accomplish the desired signal processing. This software architecture allows the software to scale effortlessly between single CPU/single-core computers or multi-CPU/multi-core computers without recompilation. NASA spaceflight and ground communications systems currently rely exclusively on ASICs or FPGAs. This software allows low- and medium-bandwidth (100 bps to .50 Mbps) software defined radios to be designed and implemented solely in C/C++ software, while lowering development costs and facilitating reuse and extensibility.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ben Krit, S.; Coulie-Castellani, K.; Rahajandraibe, W.
2015-07-01
A transistor level implementation of the analog block of a readout system on SOI process is presented here. This system is dedicated to the signal conditioning of a neutron detector in harsh environment. The different parts of the readout circuits are defined. The harsh environment constraints (crossing particle effect, high temperatures) are also detailed and modeled in the circuit in order to test and evaluate the characteristics of the designed block when working under these conditions. (authors)
Inta, R; Evans, T A; Lai, J C S
2009-02-01
Termite soldiers produce a vibratory alarm signal to warn conspecific workers. This study recorded and characterized the alarm signals of Coptotermes acinaciformis (Froggatt) (Isoptera: Rhinotermitidae) and then investigated the effect of playing these recorded alarm signals on C. acinaciformis feeding activity. Foraging groups of termites were offered paired wooden blocks: either one block, continuously stimulated with a vibratory alarm signal, paired with a nonstimulated block (the alarm treatment), continuously stimulated with a pink noise signal, paired with a nonstimulated block (control for nonspecific vibrations) or two nonstimulated blocks (control for environmental effects), for 4 wk. The amount of wood eaten in the blocks stimulated by the alarm signals was significantly less than the paired nonstimulated blocks, while there seemed to be no preference in the case of the pink noise playback or control for direction. Importantly, the termites seemed not to have adapted to the recorded alarm signal over the 4-wk duration of the experiment, unlike previous studies using nonbiologically derived signals.
PI3K inhibitors block skeletogenesis but not patterning in sea urchin embryos.
Bradham, C A; Miranda, E L; McClay, D R
2004-04-01
Skeletogenesis in the sea urchin embryo is a simple model of biomineralization, pattern formation, and cell-cell communication during embryonic development. The calcium carbonate skeletal spicules are secreted by primary mesenchyme cells (PMCs), but the skeletal pattern is dictated by the embryonic ectoderm. Although the process of skeletogenesis is well characterized, there is little molecular understanding of the basis of patterning within this system. In this study, we examined the contribution of phosphatidylinositide 3-kinase (PI3K)-mediated signaling to the skeletogenic process in sea urchin embryos by using the well-established PI3K inhibitors LY294002 and wortmannin. Our results show that PI3K inhibitors specifically and reversibly block skeletogenesis, and that this blockade occurs within the PMCs rather than in the ectoderm, because the inhibitors block spiculogenesis in cultured micromeres. Our results are consistent with a model in which PI3K signaling is required, not for pattern sensing or interpretation but rather for the biomineralization process itself in the sea urchin embryo. Copyright 2004 Wiley-Liss, Inc.
Integrated mixed signal control IC for 500-kHz switching frequency buck regulator
NASA Astrophysics Data System (ADS)
Chen, Keng; Zhang, Hong
2015-12-01
The main purpose for this work is to study the challenges of designing a digital buck regulator using pipelined analog to digital converter (ADC). Although pipelined ADC can achieve high sampling speed, it will introduce additional phase lag to the buck circuit. Along with the latency brought by processing time of additional digital circuits, as well as the time delay associated with the switching frequency, the closed loop will be unstable; moreover, raw ADC outputs have low signal-to-noise ratio, which usually need back-end calibration. In order to compensate these phase lag and make control loop unconditional stable, as well as boost up signal-to-noise ratio of the ADC block with cost-efficient design, a finite impulse response filter followed by digital proportional-integral-derivative blocks were designed. All these digital function blocks were optimised with processing speed. In the system simulation, it can be found that this controller achieved output regulation within 10% of nominal 5 V output voltage under 1 A/µs load transient condition; moreover, with the soft-start method, there is no turn-on overshooting. The die size of this controller is controlled within 3 mm2 by using 180 nm CMOS technology.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 4 2010-10-01 2010-10-01 false Cab signal indication when locomotive enters block... Systems Standards § 236.512 Cab signal indication when locomotive enters block where restrictive... within a block, wherein any condition described in § 236.205 obtains, the cab signals shall indicate...
49 CFR 236.827 - System, block signal.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 49 Transportation 4 2014-10-01 2014-10-01 false System, block signal. 236.827 Section 236.827..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.827 System, block signal. A method of governing the movement of trains into or within one or more blocks by...
49 CFR 236.827 - System, block signal.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 49 Transportation 4 2013-10-01 2013-10-01 false System, block signal. 236.827 Section 236.827..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.827 System, block signal. A method of governing the movement of trains into or within one or more blocks by...
Higher-order associative processing in Hermissenda suggests multiple sites of neuronal modulation.
Rogers, R F; Matzel, L D
1996-01-01
Two important features of modern accounts of associative learning are (1) the capacity for contextual stimuli to serve as a signal for an unconditioned stimulus (US) and (2) the capacity for a previously conditioned (excitatory) stimulus to "block" learning about a redundant stimulus when both stimuli serve as a signal for the same US. Here, we examined the process of blocking, thought by some to reflect a cognitive aspect of classical conditioning, and its underlying mechanisms in the marine mollusc Hermissenda. In two behavioral experiments, a context defined by chemosensory stimuli was made excitatory by presenting unsignalled USs (rotation) in that context. The excitatory context subsequently blocked overt learning about a discrete conditioned stimulus (CS; light) paired with the US in that context. In a third experiment, the excitability of the B photoreceptors in the Hermissenda eye, which typically increases following light-rotation pairings, was examined in behaviorally blocked animals, as well as in animals that had acquired a normal CS-US association or animals that had been exposed to the CS and US unpaired. Both the behaviorally blocked and the "normal" learning groups exhibited increases in neuronal excitability relative to unpaired animals. However, light-induced multiunit activity in pedal nerves was suppressed following normal conditioning but not in blocked or unpaired control animals, suggesting that the expression of blocking is mediated by neuronal modifications not directly reflected in B-cell excitability, possibly within an extensive network of central light-responsive interneurons.
Digital tanlock loop architecture with no delay
NASA Astrophysics Data System (ADS)
Al-Kharji AL-Ali, Omar; Anani, Nader; Al-Araji, Saleh; Al-Qutayri, Mahmoud; Ponnapalli, Prasad
2012-02-01
This article proposes a new architecture for a digital tanlock loop which eliminates the time-delay block. The ? (rad) phase shift relationship between the two channels, which is generated by the delay block in the conventional time-delay digital tanlock loop (TDTL), is preserved using two quadrature sampling signals for the loop channels. The proposed system outperformed the original TDTL architecture, when both systems were tested with frequency shift keying input signal. The new system demonstrated better linearity and acquisition speed as well as improved noise performance compared with the original TDTL architecture. Furthermore, the removal of the time-delay block enables all processing to be digitally performed, which reduces the implementation complexity. Both the original TDTL and the new architecture without the delay block were modelled and simulated using MATLAB/Simulink. Implementation issues, including complexity and relation to simulation of both architectures, are also addressed.
NASA Astrophysics Data System (ADS)
Hibert, Clément; Provost, Floriane; Malet, Jean-Philippe; Bourrier, Franck; Berger, Frédéric; Bornemann, Pierrick; Borgniet, Laurent; Tardif, Pascal; Mermin, Eric
2016-04-01
Understanding the dynamics of rockfalls is critical to mitigate the associated hazards but is made very difficult by the nature of these natural disasters that makes them hard to observe directly. Recent advances in seismology allow to determine the dynamics of the largest landslides on Earth from the very low-frequency seismic waves they generate. However, the vast majority of rockfalls that occur worldwide are too small to generate such low-frequency seismic waves and thus these methods cannot be used to reconstruct their dynamics. However, if seismic sensors are close enough, these events will generate high-frequency seismic signals. Unfortunately we cannot yet use these high-frequency seismic records to infer parameters synthetizing the rockfall dynamics as the source of these waves is not well understood. One of the first steps towards understanding the physical processes involved in the generation of high-frequency seismic waves by rockfalls is to study the link between the dynamics of a single block propagating along a well-known path and the features of the seismic signal generated. We conducted controlled releases of single blocks of limestones in a gully of clay-shales (e.g. black marls) in the Rioux Bourdoux torrent (French Alps). 28 blocks, with masses ranging from 76 kg to 472 kg, were released. A monitoring network combining high-velocity cameras, a broadband seismometer and an array of 4 high-frequency seismometers was deployed near the release area and along the travel path. The high-velocity cameras allow to reconstruct the 3D trajectories of the blocks, to estimate their velocities and the position of the different impacts with the slope surface. These data are compared to the seismic signals recorded. As the distance between the block and the seismic sensors at the time of each impact is known, we can determine the associated seismic signal amplitude corrected from propagation and attenuation effects. We can further compare the velocity, the energy and the momentum of the block at each impact to the true amplitude and the energy of the corresponding part of the seismic signal. Finding potential correlations and scaling laws between the dynamics of the source and the high-frequency seismic signal features constitutes an important breakthrough to understand more complex slope movements that involve multiple blocks or granular flows. This approach may lead to future developments of methods able to determine the dynamics of a large variety of slope movements directly from the seismic signals they generate.
Traveling Rocky Roads: The Consequences of Transcription-Blocking DNA Lesions on RNA Polymerase II.
Steurer, Barbara; Marteijn, Jurgen A
2017-10-27
The faithful transcription of eukaryotic genes by RNA polymerase II (RNAP2) is crucial for proper cell function and tissue homeostasis. However, transcription-blocking DNA lesions of both endogenous and environmental origin continuously challenge the progression of elongating RNAP2. The stalling of RNAP2 on a transcription-blocking lesion triggers a series of highly regulated events, including RNAP2 processing to make the lesion accessible for DNA repair, R-loop-mediated DNA damage signaling, and the initiation of transcription-coupled DNA repair. The correct execution and coordination of these processes is vital for resuming transcription following the successful repair of transcription-blocking lesions. Here, we outline recent insights into the molecular consequences of RNAP2 stalling on transcription-blocking DNA lesions and how these lesions are resolved to restore mRNA synthesis. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Duque, Julie; Labruna, Ludovica; Cazares, Christian; Ivry, Richard B
2014-12-01
Motor behavior requires selecting between potential actions. The role of inhibition in response selection has frequently been examined in tasks in which participants are engaged in some advance preparation prior to the presentation of an imperative signal. Under such conditions, inhibition could be related to processes associated with response selection, or to more general inhibitory processes that are engaged in high states of anticipation. In Experiment 1, we manipulated the degree of anticipatory preparation. Participants performed a choice reaction time task that required choosing between a movement of the left or right index finger, and used transcranial magnetic stimulation (TMS) to elicit motor evoked potentials (MEPs) in the left hand agonist. In high anticipation blocks, a non-informative cue (e.g., fixation marker) preceded the imperative; in low anticipation blocks, there was no cue and participants were required to divide their attention between two tasks to further reduce anticipation. MEPs were substantially reduced before the imperative signal in high anticipation blocks. In contrast, in low anticipation blocks, MEPs remained unchanged before the imperative signal but showed a marked suppression right after the onset of the imperative. This effect occurred regardless of whether the imperative had signalled a left or right hand response. After this initial inhibition, left MEPs increased when the left hand was selected and remained suppressed when the right hand was selected. We obtained similar results in Experiment 2 except that the persistent left MEP suppression when the left hand was not selected was attenuated when the alternative response involved a non-homologous effector (right foot). These results indicate that, even in the absence of an anticipatory period, inhibitory mechanisms are engaged during response selection, possibly to prevent the occurrence of premature and inappropriate responses during a competitive selection process. Copyright © 2014 Elsevier Ltd. All rights reserved.
49 CFR 236.504 - Operation interconnected with automatic block-signal system.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 4 2010-10-01 2010-10-01 false Operation interconnected with automatic block... Operation interconnected with automatic block-signal system. (a) A continuous inductive automatic train stop or train control system shall operate in connection with an automatic block signal system and shall...
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 4 2010-10-01 2010-10-01 false Block. 236.708 Section 236.708 Transportation... OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.708 Block. A length of track of defined limits, the use of which by trains is governed by block signals, cab signals, or both. ...
Analysis of automobile engine cylinder pressure and rotation speed from engine body vibration signal
NASA Astrophysics Data System (ADS)
Wang, Yuhua; Cheng, Xiang; Tan, Haishu
2016-01-01
In order to improve the engine vibration signal process method for the engine cylinder pressure and engine revolution speed measurement instrument, the engine cylinder pressure varying with the engine working cycle process has been regarded as the main exciting force for the engine block forced vibration. The forced vibration caused by the engine cylinder pressure presents as a low frequency waveform which varies with the cylinder pressure synchronously and steadily in time domain and presents as low frequency high energy discrete humorous spectrum lines in frequency domain. The engine cylinder pressure and the rotation speed can been extract form the measured engine block vibration signal by low-pass filtering analysis in time domain or by FFT analysis in frequency domain, the low-pass filtering analysis in time domain is not only suitable for the engine in uniform revolution condition but also suitable for the engine in uneven revolution condition. That provides a practical and convenient way to design motor revolution rate and cylinder pressure measurement instrument.
NASA Astrophysics Data System (ADS)
Kepner, J. V.; Janka, R. S.; Lebak, J.; Richards, M. A.
1999-12-01
The Vector/Signal/Image Processing Library (VSIPL) is a DARPA initiated effort made up of industry, government and academic representatives who have defined an industry standard API for vector, signal, and image processing primitives for real-time signal processing on high performance systems. VSIPL supports a wide range of data types (int, float, complex, ...) and layouts (vectors, matrices and tensors) and is ideal for astronomical data processing. The VSIPL API is intended to serve as an open, vendor-neutral, industry standard interface. The object-based VSIPL API abstracts the memory architecture of the underlying machine by using the concept of memory blocks and views. Early experiments with VSIPL code conversions have been carried out by the High Performance Computing Program team at the UCSD. Commercially, several major vendors of signal processors are actively developing implementations. VSIPL has also been explicitly required as part of a recent Rome Labs teraflop procurement. This poster presents the VSIPL API, its functionality and the status of various implementations.
A Robust High-Performance GPS L1 Receiver with Single-stage Quadrature Redio-Frequency Circuit
NASA Astrophysics Data System (ADS)
Liu, Jianghua; Xu, Weilin; Wan, Qinq; Liu, Tianci
2018-03-01
A low power current reuse single-stage quadrature raido-frequency part (SQRF) is proposed for GPS L1 receiver in 180nm CMOS process. The proposed circuit consists of LNA, Mixer, QVCO, is called the QLMV cell. A two blocks stacked topology is adopted in this design. The parallel QVCO and mixer placed on the top forms the upper stacked block, and the LNA placed on the bottom forms the other stacked block. The two blocks share the current and achieve low power performance. To improve the stability, a float current source is proposed. The float current isolated the local oscillation signal and the input RF signal, which bring the whole circuit robust high-performance. The result shows conversion gain is 34 dB, noise figure is three dB, the phase noise is -110 dBc/Hz at 1MHz and IIP3 is -20 dBm. The proposed circuit dissipated 1.7mW with 1 V supply voltage.
An Energy Efficient ECG Signal Processor Detecting Cardiovascular Diseases on Smartphone.
Jain, Sanjeev Kumar; Bhaumik, Basabi
2017-04-01
A novel disease diagnostic algorithm for ECG signal processing based on forward search is implemented in Application Specific Integrated Circuit (ASIC) for cardiovascular disease diagnosis on smartphone. An ASIC is fabricated using 130-nm CMOS low leakage process technology. The area of our PQRST ASIC is 1.21 mm 2 . The energy dissipation of PQRST ASIC is 96 pJ with a supply voltage of 0.9 V. The outputs from the ASIC are fed to an Android application that generates diagnostic report and can be sent to a cardiologist via email. The ASIC and Android application are verified for the detection of bundle branch block, hypertrophy, arrhythmia and myocardial infarction using Physionet PTB diagnostic ECG database. The failed detection rate is 0.69%, 0.69%, 0.34% and 1.72% for bundle branch block, hypertrophy, arrhythmia and myocardial infarction respectively. The AV block is detected in all the three patients in the Physionet St. Petersburg arrhythmia database. Our proposed ASIC together with our Android application is the most suitable for an energy efficient wearable cardiovascular disease detection system.
NASA Astrophysics Data System (ADS)
Dong, Sunghee; Jeong, Jichai
2018-02-01
Objective. Memory is formed by the interaction of various brain functions at the item and task level. Revealing individual and combined effects of item- and task-related processes on retrieving episodic memory is an unsolved problem because of limitations in existing neuroimaging techniques. To investigate these issues, we analyze fast and slow optical signals measured from a custom-built continuous wave functional near-infrared spectroscopy (CW-fNIRS) system. Approach. In our work, we visually encode the words to the subjects and let them recall the words after a short rest. The hemodynamic responses evoked by the episodic memory are compared with those evoked by the semantic memory in retrieval blocks. In the fast optical signal, we compare the effects of old and new items (previously seen and not seen) to investigate the item-related process in episodic memory. The Kalman filter is simultaneously applied to slow and fast optical signals in different time windows. Main results. A significant task-related HbR decrease was observed in the episodic memory retrieval blocks. Mean amplitude and peak latency of a fast optical signal are dependent upon item types and reaction time, respectively. Moreover, task-related hemodynamic and item-related fast optical responses are correlated in the right prefrontal cortex. Significance. We demonstrate that episodic memory is retrieved from the right frontal area by a functional connectivity between the maintained mental state through retrieval and item-related transient activity. To the best of our knowledge, this demonstration of functional NIRS research is the first to examine the relationship between item- and task-related memory processes in the prefrontal area using single modality.
Dong, Sunghee; Jeong, Jichai
2018-02-01
Memory is formed by the interaction of various brain functions at the item and task level. Revealing individual and combined effects of item- and task-related processes on retrieving episodic memory is an unsolved problem because of limitations in existing neuroimaging techniques. To investigate these issues, we analyze fast and slow optical signals measured from a custom-built continuous wave functional near-infrared spectroscopy (CW-fNIRS) system. In our work, we visually encode the words to the subjects and let them recall the words after a short rest. The hemodynamic responses evoked by the episodic memory are compared with those evoked by the semantic memory in retrieval blocks. In the fast optical signal, we compare the effects of old and new items (previously seen and not seen) to investigate the item-related process in episodic memory. The Kalman filter is simultaneously applied to slow and fast optical signals in different time windows. A significant task-related HbR decrease was observed in the episodic memory retrieval blocks. Mean amplitude and peak latency of a fast optical signal are dependent upon item types and reaction time, respectively. Moreover, task-related hemodynamic and item-related fast optical responses are correlated in the right prefrontal cortex. We demonstrate that episodic memory is retrieved from the right frontal area by a functional connectivity between the maintained mental state through retrieval and item-related transient activity. To the best of our knowledge, this demonstration of functional NIRS research is the first to examine the relationship between item- and task-related memory processes in the prefrontal area using single modality.
NASA Astrophysics Data System (ADS)
Weber, Walter H.; Mair, H. Douglas; Jansen, Dion
2003-03-01
A suite of basic signal processors has been developed. These basic building blocks can be cascaded together to form more complex processors without the need for programming. The data structures between each of the processors are handled automatically. This allows a processor built for one purpose to be applied to any type of data such as images, waveform arrays and single values. The processors are part of Winspect Data Acquisition software. The new processors are fast enough to work on A-scan signals live while scanning. Their primary use is to extract features, reduce noise or to calculate material properties. The cascaded processors work equally well on live A-scan displays, live gated data or as a post-processing engine on saved data. Researchers are able to call their own MATLAB or C-code from anywhere within the processor structure. A built-in formula node processor that uses a simple algebraic editor may make external user programs unnecessary. This paper also discusses the problems associated with ad hoc software development and how graphical programming languages can tie up researchers writing software rather than designing experiments.
In-situ roundness measurement and correction for pin journals in oscillating grinding machines
NASA Astrophysics Data System (ADS)
Yu, Hongxiang; Xu, Mengchen; Zhao, Jie
2015-01-01
In the mass production of vehicle-engine crankshafts, pin chasing grinding using oscillating grinding machines is a widely accepted method to achieve flexible and efficient performance. However, the eccentric movement of pin journals makes it difficult to develop an in-process roundness measurement scheme for the improvement of contour precision. Here, a new in-situ roundness measurement strategy is proposed with high scanning speed. The measuring mechanism is composed of a V-block and an adaptive telescopic support. The swing pattern of the telescopic support and the V-block is analysed for an equal angle-interval signal sampling. Hence roundness error signal is extracted in frequency domain using a small-signal model of the V-block roundness measurement method and the Fast Fourier Transformation. To implement the roundness data in the CNC coordinate system of an oscillating grinding machine, a transformation function is derived according to the motion model of pin chasing grinding methodology. Computer simulation reveals the relationship between the rotational position of the crankshaft component and the scanning angle of the displacement probe on the V-block, as well as the influence introduced by the rotation centre drift. Prototype investigation indicates the validity of the theoretical analysis and the feasibility of the new strategy.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 4 2010-10-01 2010-10-01 false Automatic block signal system and interlocking standards applicable to traffic control systems. 236.401 Section 236.401 Transportation Other Regulations... block signal system and interlocking standards applicable to traffic control systems. The standards...
Numerical modelling of distributed vibration sensor based on phase-sensitive OTDR
NASA Astrophysics Data System (ADS)
Masoudi, A.; Newson, T. P.
2017-04-01
A Distributed Vibration Sensor Based on Phase-Sensitive OTDR is numerically modeled. The advantage of modeling the building blocks of the sensor individually and combining the blocks to analyse the behavior of the sensing system is discussed. It is shown that the numerical model can accurately imitate the response of the experimental setup to dynamic perturbations a signal processing procedure similar to that used to extract the phase information from sensing setup.
Cell surface GRP78 facilitates hepatoma cells proliferation and migration by activating IGF-IR.
Yin, Yancun; Chen, Chen; Chen, Jinliang; Zhan, Renhui; Zhang, Qiang; Xu, Xiaoyan; Li, Defang; Li, Minjing
2017-07-01
The 78kDa glucose regulated protein (GRP78) is a multifunctional chaperone that is involved in a variety of cellular processes. Insulin like growth factor I receptor (IGF-IR) often aberrant expresses in many types of tumor cells. The IGF-IR signaling plays key roles in carcinogenesis and maintenance of the malignant phenotype. The crosstalk between GRP78 and IGF-IR molecules has not well been illuminated. Here, we demonstrated a reciprocal regulation of GRP78 expression and IGF-IR pathway activation. IGF-I induced GRP78 expression in hepatoma cells. IGF-IR knockdown or IGF-IR inhibitor repressed GRP78 expression. Both phosphatidylinositol 3-kianase (PI3K) and mitogen-activated protein kinase (MAPK) pathways involved in IGF-I induction of GRP78 expression. Interestingly, treatment of hepatoma cells with IGF-I re-distributes GRP78 from endoplasmic reticulum (ER) to cell surface and promotes its physical interaction with IGF-IR. Also, GRP78 promotes IGF-IR phosphorylation and activation. Blocked of GRP78 by small interfering RNA or inhibition of GRP78 function by (-)-epigallocatechin gallate (EGCG) blocks IGF-I induced IGF-IR phosphorylation and its downstream signaling. Further, blocked cell surface GRP78 with antibody inhibits IGF-I stimulated cellular proliferation and migration. These data reveal an essential role for the molecular chaperone GRP78 in IGF-IR signaling and implicate the use of GRP78 inhibitors in blocking IGF-IR signaling in hepatoma cells. Copyright © 2017 Elsevier Inc. All rights reserved.
NASA Technical Reports Server (NTRS)
Bahr, Christopher J.; Brooks, Thomas F.; Humphreys, William M.; Spalt, Taylor B.; Stead, Daniel J.
2014-01-01
An advanced vehicle concept, the HWB N2A-EXTE aircraft design, was tested in NASA Langley's 14- by 22-Foot Subsonic Wind Tunnel to study its acoustic characteristics for var- ious propulsion system installation and airframe con gurations. A signi cant upgrade to existing data processing systems was implemented, with a focus on portability and a re- duction in turnaround time. These requirements were met by updating codes originally written for a cluster environment and transferring them to a local workstation while en- abling GPU computing. Post-test, additional processing of the time series was required to remove transient hydrodynamic gusts from some of the microphone time series. A novel automated procedure was developed to analyze and reject contaminated blocks of data, under the assumption that the desired acoustic signal of interest was a band-limited sta- tionary random process, and of lower variance than the hydrodynamic contamination. The procedure is shown to successfully identify and remove contaminated blocks of data and retain the desired acoustic signal. Additional corrections to the data, mainly background subtraction, shear layer refraction calculations, atmospheric attenuation and microphone directivity corrections, were all necessary for initial analysis and noise assessments. These were implemented for the post-processing of spectral data, and are shown to behave as expected.
EMG amplifier with wireless data transmission
NASA Astrophysics Data System (ADS)
Kowalski, Grzegorz; Wildner, Krzysztof
2017-08-01
Wireless medical diagnostics is a trend in modern technology used in medicine. This paper presents a concept of realization, architecture of hardware and software implementation of an elecromyography signal (EMG) amplifier with wireless data transmission. This amplifier consists of three components: analogue processing of bioelectric signal module, micro-controller circuit and an application enabling data acquisition via a personal computer. The analogue bioelectric signal processing circuit receives electromyography signals from the skin surface, followed by initial analogue processing and preparation of the signals for further digital processing. The second module is a micro-controller circuit designed to wirelessly transmit the electromyography signals from the analogue signal converter to a personal computer. Its purpose is to eliminate the need for wired connections between the patient and the data logging device. The third block is a computer application designed to display the transmitted electromyography signals, as well as data capture and analysis. Its purpose is to provide a graphical representation of the collected data. The entire device has been thoroughly tested to ensure proper functioning. In use, the device displayed the captured electromyography signal from the arm of the patient. Amplitude- frequency characteristics were set in order to investigate the bandwidth and the overall gain of the device.
Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis.
Halder, Sunil K; Beauchamp, R Daniel; Datta, Pran K
2005-07-01
Smad proteins play a key role in the intracellular signaling of the transforming growth factor beta (TGF-beta) superfamily of extracellular polypeptides that initiate signaling to regulate a wide variety of biological processes. The inhibitory Smad, Smad7, has been shown to function as intracellular antagonists of TGF-beta family signaling and is upregulated in several cancers. To determine the effect of Smad7-mediated blockade of TGF-beta signaling, we have stably expressed Smad7 in a TGF-beta-sensitive, well-differentiated, and non-tumorigenic cell line, FET, that was derived from human colon adenocarcinoma. Smad7 inhibits TGF-beta-induced transcriptional responses by blocking complex formation between Smad 2/3 and Smad4. While Smad7 has no effect on TGF-beta-induced activation of p38 MAPK and ERK, it blocks the phosphorylation of Akt by TGF-beta and enhances TGF-beta-induced phosphorylation of c-Jun. FET cells expressing Smad7 show anchorage-independent growth and enhance tumorigenicity in athymic nude mice. Smad7 blocks TGF-beta-induced growth inhibition by preventing TGF-beta-induced G1 arrest. Smad7 inhibits TGF-beta-mediated downregulation of c-Myc, CDK4, and Cyclin D1, and suppresses the expression of p21(Cip1). As a result, Smad7 inhibits TGF-beta-mediated downregulation of Rb phosphorylation. Furthermore, Smad7 inhibits the apoptosis of these cells. Together, Smad7 may increase the tumorigenicity of FET cells by blocking TGF-beta-induced growth inhibition and by inhibiting apoptosis. Thus, this study provides a mechanism by which a portion of human colorectal tumors may become refractory to tumor-suppressive actions of TGF-beta that might result in increased tumorigenicity.
1984-08-01
90de It noce..etrv wnd identify by block numberl .’-- This work reviews the areas of monaural and binaural signal detection, auditory discrimination And...AUDITORY DISPLAYS This work reviews the areas of monaural and binaural signal detection, auditory discrimination and localization, and reaction times to...pertaining to the major areas of auditory processing in humans. The areas covered in the reviews presented here are monaural and binaural siqnal detection
Wiley, J C; Wailes, L A; Idzerda, R L; McKnight, G S
1999-03-05
Regulation of protein kinase A by subcellular localization may be critical to target catalytic subunits to specific substrates. We employed epitope-tagged catalytic subunit to correlate subcellular localization and gene-inducing activity in the presence of regulatory subunit or protein kinase inhibitor (PKI). Transiently expressed catalytic subunit distributed throughout the cell and induced gene expression. Co-expression of regulatory subunit or PKI blocked gene induction and prevented nuclear accumulation. A mutant PKI lacking the nuclear export signal blocked gene induction but not nuclear accumulation, demonstrating that nuclear export is not essential to inhibit gene induction. When the catalytic subunit was targeted to the nucleus with a nuclear localization signal, it was not sequestered in the cytoplasm by regulatory subunit, although its activity was completely inhibited. PKI redistributed the nuclear catalytic subunit to the cytoplasm and blocked gene induction, demonstrating that the nuclear export signal of PKI can override a strong nuclear localization signal. With increasing PKI, the export process appeared to saturate, resulting in the return of catalytic subunit to the nucleus. These results demonstrate that both the regulatory subunit and PKI are able to completely inhibit the gene-inducing activity of the catalytic subunit even when the catalytic subunit is forced to concentrate in the nuclear compartment.
Kast, Richard E; Skuli, Nicolas; Cos, Samuel; Karpel-Massler, Georg; Shiozawa, Yusuke; Goshen, Ran; Halatsch, Marc-Eric
2017-01-01
Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities. Chemotherapy, radiation, and surgery provoke EMT in cancer generally and in breast cancer specifically. ABC7 uses standard doses of capecitabine as used in treating breast cancer today. In addition, ABC7 uses 1) an older psychiatric drug, quetiapine, to block RANK signaling; 2) pirfenidone, an anti-fibrosis drug to block TGF-beta signaling; 3) rifabutin, an antibiotic to block beta-catenin signaling; 4) metformin, a first-line antidiabetic drug to stimulate AMPK and inhibit mammalian target of rapamycin, (mTOR); 5) propranolol, a beta-blocker to block beta-adrenergic signaling; 6) agomelatine, a melatonergic antidepressant to stimulate M1 and M2 melatonergic receptors; and 7) ribavirin, an antiviral drug to prevent eIF4E phosphorylation. All these block the signaling pathways - RANK, TGF-beta, mTOR, beta-adrenergic receptors, and phosphorylated eIF4E - that have been shown to trigger EMT and enhance breast cancer growth and so are worthwhile targets to inhibit. Agonism at MT1 and MT2 melatonergic receptors has been shown to inhibit both breast cancer EMT and growth. This ensemble was designed to be safe and augment capecitabine efficacy. Given the expected outcome of metastatic breast cancer as it stands today, ABC7 warrants a cautious trial.
A microprogrammable radar controller
NASA Technical Reports Server (NTRS)
Law, D. C.
1986-01-01
The Wave Propagation Lab. has completed the design and construction of a microprogrammable radar controller for atmospheric wind profiling. Unlike some radar controllers using state machines or hardwired logic for radar timing, this design is a high speed programmable sequencer with signal processing resources. A block diagram of the device is shown. The device is a single 8 1/2 inch by 10 1/2 inch printed circuit board and consists of three main subsections: (1) the host computer interface; (2) the microprogram sequencer; and (3) the signal processing circuitry. Each of these subsections are described in detail.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 4 2010-10-01 2010-10-01 false Cab signals controlled in accordance with block conditions stopping distance in advance. 236.511 Section 236.511 Transportation Other Regulations Relating to... § 236.511 Cab signals controlled in accordance with block conditions stopping distance in advance. The...
Karayiannis, Nicolaos B; Sami, Abdul; Frost, James D; Wise, Merrill S; Mizrahi, Eli M
2005-04-01
This paper presents an automated procedure developed to extract quantitative information from video recordings of neonatal seizures in the form of motor activity signals. This procedure relies on optical flow computation to select anatomical sites located on the infants' body parts. Motor activity signals are extracted by tracking selected anatomical sites during the seizure using adaptive block matching. A block of pixels is tracked throughout a sequence of frames by searching for the most similar block of pixels in subsequent frames; this search is facilitated by employing various update strategies to account for the changing appearance of the block. The proposed procedure is used to extract temporal motor activity signals from video recordings of neonatal seizures and other events not associated with seizures.
Analog integrated circuits design for processing physiological signals.
Li, Yan; Poon, Carmen C Y; Zhang, Yuan-Ting
2010-01-01
Analog integrated circuits (ICs) designed for processing physiological signals are important building blocks of wearable and implantable medical devices used for health monitoring or restoring lost body functions. Due to the nature of physiological signals and the corresponding application scenarios, the ICs designed for these applications should have low power consumption, low cutoff frequency, and low input-referred noise. In this paper, techniques for designing the analog front-end circuits with these three characteristics will be reviewed, including subthreshold circuits, bulk-driven MOSFETs, floating gate MOSFETs, and log-domain circuits to reduce power consumption; methods for designing fully integrated low cutoff frequency circuits; as well as chopper stabilization (CHS) and other techniques that can be used to achieve a high signal-to-noise performance. Novel applications using these techniques will also be discussed.
Non-signalling energy use in the developing rat brain
Engl, Elisabeth; Jolivet, Renaud; Hall, Catherine N
2016-01-01
Energy use in the brain constrains its information processing power, but only about half the brain's energy consumption is directly related to information processing. Evidence for which non-signalling processes consume the rest of the brain's energy has been scarce. For the first time, we investigated the energy use of the brain's main non-signalling tasks with a single method. After blocking each non-signalling process, we measured oxygen level changes in juvenile rat brain slices with an oxygen-sensing microelectrode and calculated changes in oxygen consumption throughout the slice using a modified diffusion equation. We found that the turnover of the actin and microtubule cytoskeleton, followed by lipid synthesis, are significant energy drains, contributing 25%, 22% and 18%, respectively, to the rate of oxygen consumption. In contrast, protein synthesis is energetically inexpensive. We assess how these estimates of energy expenditure relate to brain energy use in vivo, and how they might differ in the mature brain. PMID:27170699
Three-Level De-Multiplexed Dual-Branch Complex Delta-Sigma Transmitter.
Arfi, Anis Ben; Elsayed, Fahmi; Aflaki, Pouya M; Morris, Brad; Ghannouchi, Fadhel M
2018-02-20
In this paper, a dual-branch topology driven by a Delta-Sigma Modulator (DSM) with a complex quantizer, also known as the Complex Delta Sigma Modulator (CxDSM), with a 3-level quantized output signal is proposed. By de-multiplexing the 3-level Delta-Sigma-quantized signal into two bi-level streams, an efficiency enhancement over the operational frequency range is achieved. The de-multiplexed signals drive a dual-branch amplification block composed of two switch-mode back-to-back power amplifiers working at peak power. A signal processing technique known as quantization noise reduction with In-band Filtering (QNRIF) is applied to each of the de-multiplexed streams to boost the overall performances; particularly the Adjacent Channel Leakage Ratio (ACLR). After amplification, the two branches are combined using a non-isolated combiner, preserving the efficiency of the transmitter. A comprehensive study on the operation of this topology and signal characteristics used to drive the dual-branch Switch-Mode Power Amplifiers (SMPAs) was established. Moreover, this work proposes a highly efficient design of the amplification block based on a back-to-back power topology performing a dynamic load modulation exploiting the non-overlapping properties of the de-multiplexed Complex DSM signal. For experimental validation, the proposed de-multiplexed 3-level Delta-Sigma topology was implemented on the BEEcube™ platform followed by the back-to-back Class-E switch-mode power amplification block. The full transceiver is assessed using a 4th-Generation mobile communications standard LTE (Long Term Evolution) standard 1.4 MHz signal with a peak to average power ratio (PAPR) of 8 dB. The dual-branch topology exhibited a good linearity and a coding efficiency of the transmitter chain higher than 72% across the band of frequency from 1.8 GHz to 2.7 GHz.
Twofold processing for denoising ultrasound medical images.
Kishore, P V V; Kumar, K V V; Kumar, D Anil; Prasad, M V D; Goutham, E N D; Rahul, R; Krishna, C B S Vamsi; Sandeep, Y
2015-01-01
Ultrasound medical (US) imaging non-invasively pictures inside of a human body for disease diagnostics. Speckle noise attacks ultrasound images degrading their visual quality. A twofold processing algorithm is proposed in this work to reduce this multiplicative speckle noise. First fold used block based thresholding, both hard (BHT) and soft (BST), on pixels in wavelet domain with 8, 16, 32 and 64 non-overlapping block sizes. This first fold process is a better denoising method for reducing speckle and also inducing object of interest blurring. The second fold process initiates to restore object boundaries and texture with adaptive wavelet fusion. The degraded object restoration in block thresholded US image is carried through wavelet coefficient fusion of object in original US mage and block thresholded US image. Fusion rules and wavelet decomposition levels are made adaptive for each block using gradient histograms with normalized differential mean (NDF) to introduce highest level of contrast between the denoised pixels and the object pixels in the resultant image. Thus the proposed twofold methods are named as adaptive NDF block fusion with hard and soft thresholding (ANBF-HT and ANBF-ST). The results indicate visual quality improvement to an interesting level with the proposed twofold processing, where the first fold removes noise and second fold restores object properties. Peak signal to noise ratio (PSNR), normalized cross correlation coefficient (NCC), edge strength (ES), image quality Index (IQI) and structural similarity index (SSIM), measure the quantitative quality of the twofold processing technique. Validation of the proposed method is done by comparing with anisotropic diffusion (AD), total variational filtering (TVF) and empirical mode decomposition (EMD) for enhancement of US images. The US images are provided by AMMA hospital radiology labs at Vijayawada, India.
Fluoxetine Inhibits Natural Decay of Long-Term Memory via Akt/GSK-3β Signaling.
Yi, Jee Hyun; Zhang, JiaBao; Ko, Sang Yoon; Kwon, Huiyoung; Jeon, Se Jin; Park, Se Jin; Jung, Jiwook; Kim, Byung C; Lee, Young Choon; Kim, Dong Hyun; Ryu, Jong Hoon
2018-02-09
Understanding the mechanisms underlying the natural decay of long-term memory can help us find means of extending the duration of long-term memory. However, the neurobiological processes involved in the decay of long-term memory are poorly understood. In the present study, we examined the effect of acute and chronic treatment of fluoxetine on natural decay of long-term memory and the possible mechanism. Late administration of fluoxetine prolonged the persistence of long-term memory in mice, as demonstrated by object location recognition and Barnes maze tests. Fluoxetine altered Akt/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling in the hippocampus. Late short- and long-term pharmacological inhibition of GSK-3β mimicked the effect of fluoxetine on memory persistence. Pharmacological inhibition of Akt blocked the effect of fluoxetine on memory persistence. Finally, late infusion of fluoxetine increased hippocampal long-term potentiation (LTP) and pharmacological inhibition of GSK-3β blocked the natural decline in LTP. These results demonstrate that GSK-3β might be a key molecule in memory decay process, and fluoxetine extends the period of long-term memory maintenance via Akt/GSK-3β signaling.
49 CFR 236.504 - Operation interconnected with automatic block-signal system.
Code of Federal Regulations, 2011 CFR
2011-10-01
... GOVERNING THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Train Stop, Train Control and Cab Signal Systems Standards § 236.504... or train control system shall operate in connection with an automatic block signal system and shall...
NASA Astrophysics Data System (ADS)
Nazihah Mat Daud, Anis; Jaafar, Rosly; Kadri Ayop, Shahrul; Supar Rohani, Md
2018-04-01
This paper discusses the development of a computerized acoustic characterization system of non-porous solid tissue mimicking materials. This system employs an alternative pulse echo immersion technique and consists of a pulser/receiver generator, a transducer used as both a transmitter and a receiver, a digital oscilloscope, and a personal computer with a custom-developed program installed. The program was developed on the LabVIEW 2012 platform and comprises two main components, a user interface and a block diagram. The user interface consists of three panels: a signal acquisition and selection panel, a display panel, and a calculation panel. The block diagram comprises four blocks: a signal acquisition block, a peak signal analysis block, an acoustic properties calculation and display block, and an additional block. Interestingly, the system can be operated in both online and offline modes. For the online mode, the measurements are performed by connecting the system with a Rigol DS2000 Series digital oscilloscope. In contrast, the measurements are carried out by processing the saved data on the computer for the offline mode. The accuracy and consistency of the developed system was validated by a KB-Aerotech Alpha Series transducer with 5 MHz center frequency and a Rigol DS2202 two-channel 200 MHz 2 GSa s-1 digital oscilloscope, based on the measurement of the acoustic properties of three poly(methyl methacrylate) samples immersed in a medium at a temperature of (24.0 ± 0.1) °C. The findings indicated that the accuracy and consistency of the developed system was exceptionally high, within a 1.04% margin of error compared to the reference values. As such, this computerized system can be efficiently used for the acoustic characterization of non-porous solid tissues, given its spontaneous display of results, user-friendly interface, and convenient hardware connection.
Signals Involved in Tuber Wound-Healing
USDA-ARS?s Scientific Manuscript database
The induction and regulation of wound-healing (WH) processes in potato tubers and other vegetables are of great nutritional and economic importance. The rapid accumulation of waxes to restrict water vapor loss and formation of suberin barriers to block infection are crucial components of WH. Recen...
Signal-Conditioning Block of a 1 × 200 CMOS Detector Array for a Terahertz Real-Time Imaging System
Yang, Jong-Ryul; Lee, Woo-Jae; Han, Seong-Tae
2016-01-01
A signal conditioning block of a 1 × 200 Complementary Metal-Oxide-Semiconductor (CMOS) detector array is proposed to be employed with a real-time 0.2 THz imaging system for inspecting large areas. The plasmonic CMOS detector array whose pixel size including an integrated antenna is comparable to the wavelength of the THz wave for the imaging system, inevitably carries wide pixel-to-pixel variation. To make the variant outputs from the array uniform, the proposed signal conditioning block calibrates the responsivity of each pixel by controlling the gate bias of each detector and the voltage gain of the lock-in amplifiers in the block. The gate bias of each detector is modulated to 1 MHz to improve the signal-to-noise ratio of the imaging system via the electrical modulation by the conditioning block. In addition, direct current (DC) offsets of the detectors in the array are cancelled by initializing the output voltage level from the block. Real-time imaging using the proposed signal conditioning block is demonstrated by obtaining images at the rate of 19.2 frame-per-sec of an object moving on the conveyor belt with a scan width of 20 cm and a scan speed of 25 cm/s. PMID:26950128
Signal-Conditioning Block of a 1 × 200 CMOS Detector Array for a Terahertz Real-Time Imaging System.
Yang, Jong-Ryul; Lee, Woo-Jae; Han, Seong-Tae
2016-03-02
A signal conditioning block of a 1 × 200 Complementary Metal-Oxide-Semiconductor (CMOS) detector array is proposed to be employed with a real-time 0.2 THz imaging system for inspecting large areas. The plasmonic CMOS detector array whose pixel size including an integrated antenna is comparable to the wavelength of the THz wave for the imaging system, inevitably carries wide pixel-to-pixel variation. To make the variant outputs from the array uniform, the proposed signal conditioning block calibrates the responsivity of each pixel by controlling the gate bias of each detector and the voltage gain of the lock-in amplifiers in the block. The gate bias of each detector is modulated to 1 MHz to improve the signal-to-noise ratio of the imaging system via the electrical modulation by the conditioning block. In addition, direct current (DC) offsets of the detectors in the array are cancelled by initializing the output voltage level from the block. Real-time imaging using the proposed signal conditioning block is demonstrated by obtaining images at the rate of 19.2 frame-per-sec of an object moving on the conveyor belt with a scan width of 20 cm and a scan speed of 25 cm/s.
Graphical Environment Tools for Application to Gamma-Ray Energy Tracking Arrays
DOE Office of Scientific and Technical Information (OSTI.GOV)
Todd, Richard A.; Radford, David C.
2013-12-30
Highly segmented, position-sensitive germanium detector systems are being developed for nuclear physics research where traditional electronic signal processing with mixed analog and digital function blocks would be enormously complex and costly. Future systems will be constructed using pipelined processing of high-speed digitized signals as is done in the telecommunications industry. Techniques which provide rapid algorithm and system development for future systems are desirable. This project has used digital signal processing concepts and existing graphical system design tools to develop a set of re-usable modular functions and libraries targeted for the nuclear physics community. Researchers working with complex nuclear detector arraysmore » such as the Gamma-Ray Energy Tracking Array (GRETA) have been able to construct advanced data processing algorithms for implementation in field programmable gate arrays (FPGAs) through application of these library functions using intuitive graphical interfaces.« less
Saturation of recognition elements blocks evolution of new tRNA identities
Saint-Léger, Adélaïde; Bello, Carla; Dans, Pablo D.; Torres, Adrian Gabriel; Novoa, Eva Maria; Camacho, Noelia; Orozco, Modesto; Kondrashov, Fyodor A.; Ribas de Pouplana, Lluís
2016-01-01
Understanding the principles that led to the current complexity of the genetic code is a central question in evolution. Expansion of the genetic code required the selection of new transfer RNAs (tRNAs) with specific recognition signals that allowed them to be matured, modified, aminoacylated, and processed by the ribosome without compromising the fidelity or efficiency of protein synthesis. We show that saturation of recognition signals blocks the emergence of new tRNA identities and that the rate of nucleotide substitutions in tRNAs is higher in species with fewer tRNA genes. We propose that the growth of the genetic code stalled because a limit was reached in the number of identity elements that can be effectively used in the tRNA structure. PMID:27386510
Block 3 X-band receiver-exciter
NASA Technical Reports Server (NTRS)
Johns, C. E.
1987-01-01
The development of an X-band exciter, for use in the X-Band Uplink Subsystem, was completed. The exciter generates the drive signal for the X-band transmitter and also generates coherent test signals for the S- and X-band Block 3 translator and a Doppler reference signal for the Doppler extractor system. In addition to the above, the exciter generates other reference signals that are described. Also presented is an overview of the exciter design and some test data taken on the prototype. A brief discussion of the Block 3 Doppler extractor is presented.
A novel label-free cell-based assay technology using biolayer interferometry.
Verzijl, D; Riedl, T; Parren, P W H I; Gerritsen, A F
2017-01-15
Biolayer interferometry (BLI) is a well-established optical label-free technique to study biomolecular interactions. Here we describe for the first time a cell-based BLI (cBLI) application that allows label-free real-time monitoring of signal transduction in living cells. Human A431 epidermoid carcinoma cells were captured onto collagen-coated biosensors and serum-starved, followed by exposure to agonistic compounds targeting various receptors, while recording the cBLI signal. Stimulation of the epidermal growth factor receptor (EGFR) with EGF, the β 2 -adrenoceptor with dopamine, or the hepatocyte growth factor receptor (HGFR/c-MET) with an agonistic antibody resulted in distinct cBLI signal patterns. We show that the mechanism underlying the observed changes in cBLI signal is mediated by rearrangement of the actin cytoskeleton, a process referred to as dynamic mass redistribution (DMR). A panel of ligand-binding blocking and non-blocking anti-EGFR antibodies was used to demonstrate that this novel BLI application can be efficiently used as a label-free cellular assay for compound screening and characterization. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Code of Federal Regulations, 2011 CFR
2011-10-01
... TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Train Stop, Train Control and Cab Signal Systems Standards § 236.512 Cab signal indication when locomotive enters block where restrictive conditions obtain. The automatic cab signal system shall be arranged so that when a locomotive enters or is...
NASA Astrophysics Data System (ADS)
Strain, Jacob; Rathnayake, Hemali; Liu, Jinjun
2017-06-01
Semiconducting polymer nanostructures featuring bulk heterojunction (BHJ) architecture are promising light harvesters in photovoltaic (PV) devices because they allow control of individual domain sizes, internal structure and ordering, as well as well-defined contact between the electron donor and acceptor. Power conversion efficiency (PCE) of PV devices strongly depends on photoinduced dynamics. Understanding and optimizing photoinduced charge transfer processes in BHJ's hence help improve the performance of PV devices and increase their PCE in particular. We have investigated the photoinduced dynamics of a block polymer containing moieties of poly-3-hexylthiophene (P3HT) and polyanthracene (PANT) in solution and in solid state with femtosecond transient absorption (TA) spectroscopy. The dynamics of the polymer PANT alone are also studied as a control. The TA spectra of PANT includes a strong excited state absorption centered at 610 (nm) along with a stimulated emission signal stretching past the detection limit into the UV region which is absent in the monomer's spectra in the detection window. The block polymer's TA spectra strongly resembles that of P3HT but a noticeable positive pull on P3HT's stimulated emission signal residing at 575-620 (nm) is indicative of the excited state absorption of PANT in the adjacent spectral region. The doubling of the lifetime exciton delocalization on the block polymer versus P3HT alone have alluded that the lifetime of P3HT is extended by the covalent addition of PANT. The current spectroscopic investigation represents an interesting example of photoinduced processes in systems with complex energy level structure. Studies of dependence of change generation and separation on composition, dimension, and morphology of the heterojunctions are in process.
Visual information processing; Proceedings of the Meeting, Orlando, FL, Apr. 20-22, 1992
NASA Technical Reports Server (NTRS)
Huck, Friedrich O. (Editor); Juday, Richard D. (Editor)
1992-01-01
Topics discussed in these proceedings include nonlinear processing and communications; feature extraction and recognition; image gathering, interpolation, and restoration; image coding; and wavelet transform. Papers are presented on noise reduction for signals from nonlinear systems; driving nonlinear systems with chaotic signals; edge detection and image segmentation of space scenes using fractal analyses; a vision system for telerobotic operation; a fidelity analysis of image gathering, interpolation, and restoration; restoration of images degraded by motion; and information, entropy, and fidelity in visual communication. Attention is also given to image coding methods and their assessment, hybrid JPEG/recursive block coding of images, modified wavelets that accommodate causality, modified wavelet transform for unbiased frequency representation, and continuous wavelet transform of one-dimensional signals by Fourier filtering.
NASA Technical Reports Server (NTRS)
1975-01-01
Signal processing equipment specifications, operating and test procedures, and systems design and engineering are described. Five subdivisions of the overall circuitry are treated: (1) the spectrum analyzer; (2) the spectrum integrator; (3) the velocity discriminator; (4) the display interface; and (5) the formatter. They function in series: (1) first in analog form to provide frequency resolution, (2) then in digital form to achieve signal to noise improvement (video integration) and frequency discrimination, and (3) finally in analog form again for the purpose of real-time display of the significant velocity data. The formatter collects binary data from various points in the processor and provides a serial output for bi-phase recording. Block diagrams are used to illustrate the system.
The analysis of decimation and interpolation in the linear canonical transform domain.
Xu, Shuiqing; Chai, Yi; Hu, Youqiang; Huang, Lei; Feng, Li
2016-01-01
Decimation and interpolation are the two basic building blocks in the multirate digital signal processing systems. As the linear canonical transform (LCT) has been shown to be a powerful tool for optics and signal processing, it is worthwhile and interesting to analyze the decimation and interpolation in the LCT domain. In this paper, the definition of equivalent filter in the LCT domain have been given at first. Then, by applying the definition, the direct implementation structure and polyphase networks for decimator and interpolator in the LCT domain have been proposed. Finally, the perfect reconstruction expressions for differential filters in the LCT domain have been presented as an application. The proposed theorems in this study are the bases for generalizations of the multirate signal processing in the LCT domain, which can advance the filter banks theorems in the LCT domain.
Xue, Qingwang; Liu, Chunxue; Li, Xia; Dai, Li; Wang, Huaisheng
2018-04-18
Various fluorescent sensing systems for miRNA detection have been developed, but they mostly contain enzymatic amplification reactions and label procedures. The strict reaction conditions of tool enzymes and the high cost of labeling limit their potential applications, especially in complex biological matrices. Here, we have addressed the difficult problems and report a strategy for label-free fluorescent DNA dendrimers based on enzyme-free nonlinear hybridization chain reaction (HCR)-mediated multiple G-quadruplex for simple, sensitive, and selective detection of miRNAs with low-background signal. In the strategy, a split G-quadruplex (3:1) sequence is ingeniously designed at both ends of two double-stranded DNAs, which is exploited as building blocks for nonlinear HCR assembly, thereby acquiring a low background signal. A hairpin switch probe (HSP) was employed as recognition and transduction element. Upon sensing the target miRNA, the nonlinear HCR assembly of two blocks (blocks-A and blocks-B) was initiated with the help of two single-stranded DNA assistants, resulting in chain-branching growth of DNA dendrimers with multiple G-quadruplex incorporation. With the zinc(II)-protoporphyrin IX (ZnPPIX) selectively intercalated into the multiple G-quadruplexes, fluorescent DNA dendrimers were obtained, leading to an exponential fluorescence intensity increase. Benefiting from excellent performances of nonlinear HCR and low background signal, this strategy possesses the characteristics of a simplified reaction operation process, as well as high sensitivity. Moreover, the proposed fluorescent sensing strategy also shows preferable selectivity, and can be implemented without modified DNA blocks. Importantly, the strategy has also been tested for miRNA quantification with high confidence in breast cancer cells. Thus, this proposed strategy for label-free fluorescent DNA dendrimers based on a nonlinear HCR-mediated multiple G-quadruplex will be turned into an alternative approach for simple, sensitive, and selective miRNA quantification.
Pecenin, Mateus Fila; Borges-Pereira, Lucas; Levano-Garcia, Julio; Budu, Alexandre; Alves, Eduardo; Mikoshiba, Katsuhiko; Thomas, Andrew; Garcia, Celia R S
2018-03-14
Inositol 1,4,5 trisphosphate (IP 3 ) signaling plays a crucial role in a wide range of eukaryotic processes. In Plasmodium falciparum, IP 3 elicits Ca 2+ release from intracellular Ca 2+ stores, even though no IP 3 receptor homolog has been identified to date. The human host hormone melatonin plays a key role in entraining the P. falciparum life cycle in the intraerythrocytic stages, apparently through an IP 3 -dependent Ca 2+ signal. The melatonin-induced cytosolic Ca 2+ ([Ca 2+ ] cyt ) increase and malaria cell cycle can be blocked by the IP 3 receptor blocker 2-aminoethyl diphenylborinate (2-APB). However, 2-APB also inhibits store-operated Ca 2+ entry (SOCE). Therefore, we have used two novel 2-APB derivatives, DPB162-AE and DPB163-AE, which are 100-fold more potent than 2-APB in blocking SOCE in mammalian cells, and appear to act by interfering with clustering of STIM proteins. In the present work we report that DPB162-AE and DPB163-AE block the [Ca 2+ ] cyt rise in response to melatonin in P. falciparum, but only at high concentrations. These compounds also block SOCE in the parasite at similarly high concentrations suggesting that P. falciparum SOCE is not activated in the same way as in mammalian cells. We further find that DPB162-AE and DPB163-AE affect the development of the intraerythrocytic parasites and invasion of new red blood cells. Our efforts to episomally express proteins that compete with native IP 3 receptor like IP 3 -sponge and an IP 3 sensor such as IRIS proved to be lethal to P. falciparum during intraerythrocytic cycle. The present findings point to an important role of IP 3 -induced Ca 2+ release in intraerythrocytic stage of P. falciparum. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
Bi, Sheng; Zeng, Xiao; Tang, Xin; Qin, Shujia; Lai, King Wai Chiu
2016-01-01
Compressive sensing (CS) theory has opened up new paths for the development of signal processing applications. Based on this theory, a novel single pixel camera architecture has been introduced to overcome the current limitations and challenges of traditional focal plane arrays. However, video quality based on this method is limited by existing acquisition and recovery methods, and the method also suffers from being time-consuming. In this paper, a multi-frame motion estimation algorithm is proposed in CS video to enhance the video quality. The proposed algorithm uses multiple frames to implement motion estimation. Experimental results show that using multi-frame motion estimation can improve the quality of recovered videos. To further reduce the motion estimation time, a block match algorithm is used to process motion estimation. Experiments demonstrate that using the block match algorithm can reduce motion estimation time by 30%. PMID:26950127
Kast, Richard E; Skuli, Nicolas; Cos, Samuel; Karpel-Massler, Georg; Shiozawa, Yusuke; Goshen, Ran; Halatsch, Marc-Eric
2017-01-01
Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities. Chemotherapy, radiation, and surgery provoke EMT in cancer generally and in breast cancer specifically. ABC7 uses standard doses of capecitabine as used in treating breast cancer today. In addition, ABC7 uses 1) an older psychiatric drug, quetiapine, to block RANK signaling; 2) pirfenidone, an anti-fibrosis drug to block TGF-beta signaling; 3) rifabutin, an antibiotic to block beta-catenin signaling; 4) metformin, a first-line antidiabetic drug to stimulate AMPK and inhibit mammalian target of rapamycin, (mTOR); 5) propranolol, a beta-blocker to block beta-adrenergic signaling; 6) agomelatine, a melatonergic antidepressant to stimulate M1 and M2 melatonergic receptors; and 7) ribavirin, an antiviral drug to prevent eIF4E phosphorylation. All these block the signaling pathways – RANK, TGF-beta, mTOR, beta-adrenergic receptors, and phosphorylated eIF4E – that have been shown to trigger EMT and enhance breast cancer growth and so are worthwhile targets to inhibit. Agonism at MT1 and MT2 melatonergic receptors has been shown to inhibit both breast cancer EMT and growth. This ensemble was designed to be safe and augment capecitabine efficacy. Given the expected outcome of metastatic breast cancer as it stands today, ABC7 warrants a cautious trial. PMID:28744157
Wassum, Kate M.; Ostlund, Sean B.; Balleine, Bernard W.; Maidment, Nigel T.
2011-01-01
Here we attempted to clarify the role of dopamine signaling in reward seeking. In Experiment 1, we assessed the effects of the dopamine D1/D2 receptor antagonist flupenthixol (0.5 mg/kg i.p.) on Pavlovian incentive motivation and found that flupenthixol blocked the ability of a conditioned stimulus to enhance both goal approach and instrumental performance (Pavlovian-to-instrumental transfer). In Experiment 2 we assessed the effects of flupenthixol on reward palatability during post-training noncontingent re-exposure to the sucrose reward in either a control 3-h or novel 23-h food-deprived state. Flupenthixol, although effective in blocking the Pavlovian goal approach, was without effect on palatability or the increase in reward palatability induced by the upshift in motivational state. This noncontingent re-exposure provided an opportunity for instrumental incentive learning, the process by which rats encode the value of a reward for use in updating reward-seeking actions. Flupenthixol administered prior to the instrumental incentive learning opportunity did not affect the increase in subsequent off-drug reward-seeking actions induced by that experience. These data suggest that although dopamine signaling is necessary for Pavlovian incentive motivation, it is not necessary for changes in reward experience, or for the instrumental incentive learning process that translates this experience into the incentive value used to drive reward-seeking actions, and provide further evidence that Pavlovian and instrumental incentive learning processes are dissociable. PMID:21693635
Stoycheva, Diana; Deiser, Katrin; Stärck, Lilian; Nishanth, Gopala; Schlüter, Dirk; Uckert, Wolfgang; Schüler, Thomas
2015-01-15
In response to primary Ag contact, naive mouse CD8(+) T cells undergo clonal expansion and differentiate into effector T cells. After pathogen clearance, most effector T cells die, and only a small number of memory T cell precursors (TMPs) survive to form a pool of long-lived memory T cells (TMs). Although high- and low-affinity CD8(+) T cell clones are recruited into the primary response, the TM pool consists mainly of high-affinity clones. It remains unclear whether the more efficient expansion of high-affinity clones and/or cell-intrinsic processes exclude low-affinity T cells from the TM pool. In this article, we show that the lack of IFN-γR signaling in CD8(+) T cells promotes TM formation in response to weak, but not strong, TCR agonists. The IFN-γ-sensitive accumulation of TMs correlates with reduced mammalian target of rapamycin activation and the accumulation of long-lived CD62L(hi)Bcl-2(hi)Eomes(hi) TMPs. Reconstitution of mammalian target of rapamycin or IFN-γR signaling is sufficient to block this process. Hence, our data suggest that IFN-γR signaling actively blocks the formation of TMPs responding to weak TCR agonists, thereby promoting the accumulation of high-affinity T cells finally dominating the TM pool. Copyright © 2015 by The American Association of Immunologists, Inc.
Fendiline Inhibits K-Ras Plasma Membrane Localization and Blocks K-Ras Signal Transmission
van der Hoeven, Dharini; Cho, Kwang-jin; Ma, Xiaoping; Chigurupati, Sravanthi; Parton, Robert G.
2013-01-01
Ras proteins regulate signaling pathways important for cell growth, differentiation, and survival. Oncogenic mutant Ras proteins are commonly expressed in human tumors, with mutations of the K-Ras isoform being most prevalent. To be active, K-Ras must undergo posttranslational processing and associate with the plasma membrane. We therefore devised a high-content screening assay to search for inhibitors of K-Ras plasma membrane association. Using this assay, we identified fendiline, an L-type calcium channel blocker, as a specific inhibitor of K-Ras plasma membrane targeting with no detectable effect on the localization of H- and N-Ras. Other classes of L-type calcium channel blockers did not mislocalize K-Ras, suggesting a mechanism that is unrelated to calcium channel blockade. Fendiline did not inhibit K-Ras posttranslational processing but significantly reduced nanoclustering of K-Ras and redistributed K-Ras from the plasma membrane to the endoplasmic reticulum (ER), Golgi apparatus, endosomes, and cytosol. Fendiline significantly inhibited signaling downstream of constitutively active K-Ras and endogenous K-Ras signaling in cells transformed by oncogenic H-Ras. Consistent with these effects, fendiline blocked the proliferation of pancreatic, colon, lung, and endometrial cancer cell lines expressing oncogenic mutant K-Ras. Taken together, these results suggest that inhibitors of K-Ras plasma membrane localization may have utility as novel K-Ras-specific anticancer therapeutics. PMID:23129805
Kim, Jin-Man; Kim, Mi Yeong; Lee, Kyunghee; Jeong, Daewon
2016-12-05
Cell migration during specialized stages of osteoclast precursors, mononuclear preosteoclasts, and multinucleated mature osteoclasts remain uncertain. M-CSF- and osteopontin-induced osteoclastic cell migration was inhibited by function-blocking monoclonal antibodies specific to the integrin αv and β3 subunits, suggesting that integrin αvβ3 mediates migratory signaling induced by M-CSF and osteopontin. M-CSF and osteopontin stimulation was shown to regulate two branched signaling processes, PI3K/PKCα/RhoA axis and PI3K/PKCδ/Rac1 axis. Interestingly, inactivation of RhoA or Rac1 blocked preosteoclast and mature osteoclast migration but not osteoclast precursor migration in a transwell-based cell migration assay. Moreover, the inhibitory effect on preosteoclast and mature osteoclast migration induced by Rac1 inactivation was more effective than that by RhoA inactivation. Collectively, our findings suggest that osteoclast precursor migration depends on PI3K/PKCα-PKCδ signaling mediated via integrin αvβ3 bypassing RhoA and Rac1, whereas preosteoclast and mature osteoclast migration relies on PI3K/PKCα-PKCδ/RhoA-Rac1 axis signaling mediated via integrin αvβ3 with increased dependency on PKCδ/Rac1 signaling route as differentiation progresses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
FGF-mediated mesoderm induction involves the Src-family kinase Laloo.
Weinstein, D C; Marden, J; Carnevali, F; Hemmati-Brivanlou, A
1998-08-27
During embryogenesis, inductive interactions underlie the development of much of the body plan. In Xenopus laevis, factors secreted from the vegetal pole induce mesoderm in the adjacent marginal zone; members of both the transforming growth factor-beta (TGF-beta) and fibroblast growth factor (FGF) ligand families seem to have critical roles in this process. Here we report the identification and characterization of laloo, a novel participant in the signal transduction cascade linking extracellular, mesoderm-inducing signals to the nucleus, where alteration of cell fate is driven by changes in gene expression. Overexpression of laloo, a member of the Src-related gene family, in Xenopus embryos gives rise to ectopic posterior structures that frequently contain axial tissue. Laloo induces mesoderm in Xenopus ectodermal explants; this induction is blocked by reagents that disrupt the FGF signalling pathway. Conversely, expression of a dominant-inhibitory Laloo mutant blocks mesoderm induction by FGF and causes severe posterior truncations in vivo. This work provides the first evidence that a Src-related kinase is involved in vertebrate mesoderm induction.
NASA Astrophysics Data System (ADS)
Krasilenko, Vladimir G.; Nikolsky, Alexander I.; Lazarev, Alexander A.; Lazareva, Maria V.
2010-05-01
In the paper we show that the biologically motivated conception of time-pulse encoding usage gives a set of advantages (single methodological basis, universality, tuning simplicity, learning and programming et al) at creation and design of sensor systems with parallel input-output and processing for 2D structures hybrid and next generations neuro-fuzzy neurocomputers. We show design principles of programmable relational optoelectronic time-pulse encoded processors on the base of continuous logic, order logic and temporal waves processes. We consider a structure that execute analog signal extraction, analog and time-pulse coded variables sorting. We offer optoelectronic realization of such base relational order logic element, that consists of time-pulse coded photoconverters (pulse-width and pulse-phase modulators) with direct and complementary outputs, sorting network on logical elements and programmable commutation blocks. We make technical parameters estimations of devices and processors on such base elements by simulation and experimental research: optical input signals power 0.2 - 20 uW, processing time 1 - 10 us, supply voltage 1 - 3 V, consumption power 10 - 100 uW, extended functional possibilities, learning possibilities. We discuss some aspects of possible rules and principles of learning and programmable tuning on required function, relational operation and realization of hardware blocks for modifications of such processors. We show that it is possible to create sorting machines, neural networks and hybrid data-processing systems with untraditional numerical systems and pictures operands on the basis of such quasiuniversal hardware simple blocks with flexible programmable tuning.
Intermittent IL-7 Signaling Essential for T cell Homeostasis | Center for Cancer Research
In order for the immune system to mount an appropriate response to foreign antigens throughout a person’s life, the body must maintain a sufficient population of circulating mature, naïve T cells, a process known as T cell homeostasis. Previous studies revealed that this process depends upon signaling from the cytokine interleukin-7 (IL-7) as well as from the T cell antigen receptor (TCR). Intriguingly, signals from each pathway affect the other and lead to their alternating activation: IL-7 binding to its receptor leads to increasing expression of the TCR co-receptor CD8; sufficient CD8 expression allows TCRs to signal when bound to self-ligands, blocking IL-7 signaling; suppressed IL-7 signals lead to down-regulation of CD8 and ligand disengagement, which allows T cells to again respond to IL-7. Alfred Singer, M.D., and his colleagues in CCR’s Experimental Immunology Branch set out to understand how this intricate pathway promotes T cell survival.
Narasimhan, S; Chiel, H J; Bhunia, S
2011-04-01
Implantable microsystems for monitoring or manipulating brain activity typically require on-chip real-time processing of multichannel neural data using ultra low-power, miniaturized electronics. In this paper, we propose an integrated-circuit/architecture-level hardware design framework for neural signal processing that exploits the nature of the signal-processing algorithm. First, we consider different power reduction techniques and compare the energy efficiency between the ultra-low frequency subthreshold and conventional superthreshold design. We show that the superthreshold design operating at a much higher frequency can achieve comparable energy dissipation by taking advantage of extensive power gating. It also provides significantly higher robustness of operation and yield under large process variations. Next, we propose an architecture level preferential design approach for further energy reduction by isolating the critical computation blocks (with respect to the quality of the output signal) and assigning them higher delay margins compared to the noncritical ones. Possible delay failures under parameter variations are confined to the noncritical components, allowing graceful degradation in quality under voltage scaling. Simulation results using prerecorded neural data from the sea-slug (Aplysia californica) show that the application of the proposed design approach can lead to significant improvement in total energy, without compromising the output signal quality under process variations, compared to conventional design approaches.
NASA Astrophysics Data System (ADS)
Hasan, Mohammed A.
1997-11-01
In this dissertation, we present several novel approaches for detection and identification of targets of arbitrary shapes from the acoustic backscattered data and using the incident waveform. This problem is formulated as time- delay estimation and sinusoidal frequency estimation problems which both have applications in many other important areas in signal processing. Solving time-delay estimation problem allows the identification of the specular components in the backscattered signal from elastic and non-elastic targets. Thus, accurate estimation of these time delays would help in determining the existence of certain clues for detecting targets. Several new methods for solving these two problems in the time, frequency and wavelet domains are developed. In the time domain, a new block fast transversal filter (BFTF) is proposed for a fast implementation of the least squares (LS) method. This BFTF algorithm is derived by using data-related constrained block-LS cost function to guarantee global optimality. The new soft-constrained algorithm provides an efficient way of transferring weight information between blocks of data and thus it is computationally very efficient compared with other LS- based schemes. Additionally, the tracking ability of the algorithm can be controlled by varying the block length and/or a soft constrained parameter. The effectiveness of this algorithm is tested on several underwater acoustic backscattered data for elastic targets and non-elastic (cement chunk) objects. In the frequency domain, the time-delay estimation problem is converted to a sinusoidal frequency estimation problem by using the discrete Fourier transform. Then, the lagged sample covariance matrices of the resulting signal are computed and studied in terms of their eigen- structure. These matrices are shown to be robust and effective in extracting bases for the signal and noise subspaces. New MUSIC and matrix pencil-based methods are derived these subspaces. The effectiveness of the method is demonstrated on the problem of detection of multiple specular components in the acoustic backscattered data. Finally, a method for the estimation of time delays using wavelet decomposition is derived. The sub-band adaptive filtering uses discrete wavelet transform for multi- resolution or sub-band decomposition. Joint time delay estimation for identifying multi-specular components and subsequent adaptive filtering processes are performed on the signal in each sub-band. This would provide multiple 'look' of the signal at different resolution scale which results in more accurate estimates for delays associated with the specular components. Simulation results on the simulated and real shallow water data are provided which show the promise of this new scheme for target detection in a heavy cluttered environment.
Disruption of canonical TGFβ-signaling in murine coronary progenitor cells by low level arsenic
DOE Office of Scientific and Technical Information (OSTI.GOV)
Allison, Patrick; Huang, Tianfang; Broka, Derrick
2013-10-01
Exposure to arsenic results in several types of cancers as well as heart disease. A major contributor to ischemic heart pathologies is coronary artery disease, however the influences by environmental arsenic in this disease process are not known. Similarly, the impact of toxicants on blood vessel formation and function during development has not been studied. During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types including smooth muscle cells which contribute to the coronary vessels. The TGFβ family of ligands and receptors is essential for developmental cardiac epithelial to mesenchymal transition (EMT) and differentiation into coronarymore » smooth muscle cells. In this in vitro study, 18 hour exposure to 1.34 μM arsenite disrupted developmental EMT programming in murine epicardial cells causing a deficit in cardiac mesenchyme. The expression of EMT genes including TGFβ2, TGFβ receptor-3, Snail, and Has-2 are decreased in a dose-dependent manner following exposure to arsenite. TGFβ2 cell signaling is abrogated as detected by decreases in phosphorylated Smad2/3 when cells are exposed to 1.34 μM arsenite. There is also loss of nuclear accumulation pSmad due to arsenite exposure. These observations coincide with a decrease in vimentin positive mesenchymal cells invading three-dimensional collagen gels. However, arsenite does not block TGFβ2 mediated smooth muscle cell differentiation by epicardial cells. Overall these results show that arsenic exposure blocks developmental EMT gene programming in murine coronary progenitor cells by disrupting TGFβ2 signals and Smad activation, and that smooth muscle cell differentiation is refractory to this arsenic toxicity. - Highlights: • Arsenic blocks TGFβ2 induced expression of EMT genes. • Arsenic blocks TGFβ2 triggered Smad2/3 phosphorylation and nuclear translocation. • Arsenic blocks epicardial cell differentiation into cardiac mesenchyme. • Arsenic does not block TGFβ2 induced smooth muscle cell differentiation.« less
Control of Aβ release from human neurons by differentiation status and RET signaling.
Scholz, Diana; Chernyshova, Yana; Leist, Marcel
2013-01-01
Few studies have compared the processing of endogenous human amyloid precursor protein (APP) in younger and older neurons. Here, we characterized LUHMES cells as a human model to study Alzheimer's disease-related processes during neuronal maturation and aging. Differentiated LUHMES expressed and spontaneously processed APP via the secretase pathways, and they secreted amyloid β (Aβ) peptide. This was inhibited by cholesterol depletion or secretase inhibition, but not by block of tau phosphorylation. In vitro aged cells increased Aβ secretion without upregulation of APP or secretases. We identified the medium constituent glial cell line-derived neurotrophic factor (GDNF) as responsible for this effect. GDNF-triggered Aβ release was associated with rapid upregulation of the GDNF coreceptor "rearranged during transfection" (RET). Other direct (neurturin) or indirect (nerve growth factor) RET activators also increased Aβ, whereas different neurotrophins were ineffective. Downstream of RET, we found activation of protein kinase B (AKT) to be involved. Accordingly, inhibitors of the AKT regulator phosphatidylinositol-3-kinase completely blocked GDNF-triggered AKT phosphorylation and Aβ increase. This suggests that RET signaling affects Aβ release from aging neurons. Copyright © 2013 Elsevier Inc. All rights reserved.
Application of the GNU Radio platform in the multistatic radar
NASA Astrophysics Data System (ADS)
Szlachetko, Boguslaw; Lewandowski, Andrzej
2009-06-01
This document presents the application of the Software Defined Radio-based platform in the multistatic radar. This platform consists of four-sensor linear antenna, Universal Software Radio Peripheral (USRP) hardware (radio frequency frontend) and GNU-Radio PC software. The paper provides information about architecture of digital signal processing performed by USRP's FPGA (digital down converting blocks) and PC host (implementation of the multichannel digital beamforming). The preliminary results of the signal recording performed by our experimental platform are presented.
Economic Value Biases Uncertain Perceptual Choices in the Parietal and Prefrontal Cortices
Summerfield, Christopher; Koechlin, Etienne
2010-01-01
An observer detecting a noisy sensory signal is biased by the costs and benefits associated with its presence or absence. When these costs and benefits are asymmetric, sensory, and economic information must be integrated to inform the final choice. However, it remains unknown how this information is combined at the neural or computational levels. To address this question, we asked healthy human observers to judge the presence or absence of a noisy sensory signal under economic conditions that favored yes responses (liberal blocks), no responses (conservative blocks), or neither response (neutral blocks). Economic information biased fast choices more than slow choices, suggesting that value and sensory information are integrated early in the decision epoch. More formal simulation analyses using an Ornstein–Uhlenbeck process demonstrated that the influence of economic information was best captured by shifting the origin of evidence accumulation toward the more valuable bound. We then used the computational model to generate trial-by-trial estimates of decision-related evidence that were based on combined sensory and economic information (the decision variable or DV), and regressed these against fMRI activity recorded whilst participants performed the task. Extrastriate visual regions responded to the level of sensory input (momentary evidence), but fMRI signals in the parietal and prefrontal cortices responded to the decision variable. These findings support recent single-neuron data suggesting that economic information biases decision-related signals in higher cortical regions. PMID:21267421
Neurobiological hypothesis of color appearance and hue perception
Schmidt, Brian P.; Neitz, Maureen; Neitz, Jay
2014-01-01
DeValois and DeValois (1993) showed that to explain hue appearance, S-cone signals have to be combined with M vs. L opponent signals in two different ways to produce red-green and yellow-blue axes respectively. Recently, it has been shown that color appearance is normal for individuals with genetic mutations that block S-cone input to blue-on ganglion cells. This is inconsistent with the DeValois hypothesis in which S-opponent konio-geniculate signals are combined with L−M signals at a 3rd processing stage in cortex. Instead, here we show that color appearance, including individual differences never explained before, are predicted by a model in which S-cone signals are combined with L vs. M signals in the outer retina. PMID:24695170
GNU Radio Sandia Utilities v. 1.0
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gilbert, Jacob; Knee, Peter
This software adds a data handling module to the GNU Radio (GR) software defined radio (SDR) framework as well as some general-purpose function blocks (filters, metadata control, etc). This software is useful for processing bursty RF transmissions with GR, and serves as a base for applying SDR signal processing techniques to a whole burst of data at a time, as opposed to streaming data which GR has been primarily focused around.
Johnson, Adam S; García, Dana M
2007-12-19
Inside bluegill (Lepomis macrochirus) retinal pigment epithelial cells, pigment granules move in response to extracellular signals. During the process of aggregation, pigment motility is directed toward the cell nucleus; in dispersion, pigment is directed away from the nucleus and into long apical processes. A number of different chemicals have been found to initiate dispersion, and carbachol (an acetylcholine analog) is one example. Previous research indicates that the carbachol-receptor interaction activates a Gq-mediated pathway which is commonly linked to Ca2+ mobilization. The purpose of the present study was to test for involvement of calcium and to probe calcium-dependent mediators to reveal their role in carbachol-mediated dispersion. Carbachol-induced pigment granule dispersion was blocked by the calcium chelator BAPTA. In contrast, the calcium channel antagonist verapamil, and incubation in Ca2+-free medium failed to block carbachol-induced dispersion. The calcineurin inhibitor cypermethrin blocked carbachol-induced dispersion; whereas, two protein kinase C inhibitors (staurosporine and bisindolylmaleimide II) failed to block carbachol-induced dispersion, and the protein kinase C activator phorbol 12-myristate 13-acetate failed to elicit dispersion. A rise in intracellular calcium is necessary for carbachol-induced dispersion; however, the Ca2+ requirement is not dependent on extracellular sources, implying that intracellular stores are sufficient to enable pigment granule dispersion to occur. Calcineurin is a likely Ca2+-dependent mediator involved in the signal cascade. Although the pathway leads to the generation of diacylglycerol and calcium (both required for the activation of certain PKC isoforms), our evidence does not support a significant role for PKC.
Johnson, Adam S; García, Dana M
2007-01-01
Background Inside bluegill (Lepomis macrochirus) retinal pigment epithelial cells, pigment granules move in response to extracellular signals. During the process of aggregation, pigment motility is directed toward the cell nucleus; in dispersion, pigment is directed away from the nucleus and into long apical processes. A number of different chemicals have been found to initiate dispersion, and carbachol (an acetylcholine analog) is one example. Previous research indicates that the carbachol-receptor interaction activates a Gq-mediated pathway which is commonly linked to Ca2+ mobilization. The purpose of the present study was to test for involvement of calcium and to probe calcium-dependent mediators to reveal their role in carbachol-mediated dispersion. Results Carbachol-induced pigment granule dispersion was blocked by the calcium chelator BAPTA. In contrast, the calcium channel antagonist verapamil, and incubation in Ca2+-free medium failed to block carbachol-induced dispersion. The calcineurin inhibitor cypermethrin blocked carbachol-induced dispersion; whereas, two protein kinase C inhibitors (staurosporine and bisindolylmaleimide II) failed to block carbachol-induced dispersion, and the protein kinase C activator phorbol 12-myristate 13-acetate failed to elicit dispersion. Conclusion A rise in intracellular calcium is necessary for carbachol-induced dispersion; however, the Ca2+ requirement is not dependent on extracellular sources, implying that intracellular stores are sufficient to enable pigment granule dispersion to occur. Calcineurin is a likely Ca2+-dependent mediator involved in the signal cascade. Although the pathway leads to the generation of diacylglycerol and calcium (both required for the activation of certain PKC isoforms), our evidence does not support a significant role for PKC. PMID:18093324
Refining the GPS Space Service Volume (SSV) and Building a Multi-GNSS SSV
NASA Technical Reports Server (NTRS)
Parker, Joel J. K.
2017-01-01
The GPS (Global Positioning System) Space Service Volume (SSV) was first defined to protect the GPS main lobe signals from changes from block to block. First developed as a concept by NASA in 2000, it has been adopted for the GPS III block of satellites, and is being used well beyond the current specification to enable increased navigation performance for key missions like GOES-R. NASA has engaged the US IFOR (Interagency Forum Operational Requirements) process to adopt a revised requirement to protect this increased and emerging use. Also, NASA is working through the UN International Committee on GNSS (Global Navigation Satellite System) to develop an interoperable multi-GNSS SSV in partnership with all of the foreign GNSS providers.
Marchese, Michelle E.; Abdala-Valencia, Hiam
2011-01-01
Abstract The endothelium is immunoregulatory in that inhibiting the function of vascular adhesion molecules blocks leukocyte recruitment and thus tissue inflammation. The function of endothelial cells during leukocyte recruitment is regulated by reactive oxygen species (ROS) and antioxidants. In inflammatory sites and lymph nodes, the endothelium is stimulated to express adhesion molecules that mediate leukocyte binding. Upon leukocyte binding, these adhesion molecules activate endothelial cell signal transduction that then alters endothelial cell shape for the opening of passageways through which leukocytes can migrate. If the stimulation of this opening is blocked, inflammation is blocked. In this review, we focus on the endothelial cell adhesion molecule, vascular cell adhesion molecule-1 (VCAM-1). Expression of VCAM-1 is induced on endothelial cells during inflammatory diseases by several mediators, including ROS. Then, VCAM-1 on the endothelium functions as both a scaffold for leukocyte migration and a trigger of endothelial signaling through NADPH oxidase-generated ROS. These ROS induce signals for the opening of intercellular passageways through which leukocytes migrate. In several inflammatory diseases, inflammation is blocked by inhibition of leukocyte binding to VCAM-1 or by inhibition of VCAM-1 signal transduction. VCAM-1 signal transduction and VCAM-1-dependent inflammation are blocked by antioxidants. Thus, VCAM-1 signaling is a target for intervention by pharmacological agents and by antioxidants during inflammatory diseases. This review discusses ROS and antioxidant functions during activation of VCAM-1 expression and VCAM-1 signaling in inflammatory diseases. Antioxid. Redox Signal. 15, 1607–1638. PMID:21050132
Design of fast signal processing readout front-end electronics implemented in CMOS 40 nm technology
NASA Astrophysics Data System (ADS)
Kleczek, Rafal
2016-12-01
The author presents considerations on the design of fast readout front-end electronics implemented in a CMOS 40 nm technology with an emphasis on the system dead time, noise performance and power dissipation. The designed processing channel consists of a charge sensitive amplifier with different feedback types (Krummenacher, resistive and constant current blocks), a threshold setting block, a discriminator and a counter with logic circuitry. The results of schematic and post-layout simulations with randomly generated input pulses in a time domain according to the Poisson distribution are presented and analyzed. Dead time below 20 ns is possible while keeping noise ENC ≈ 90 e- for a detector capacitance CDET = 160 fF.
Digital audio watermarking using moment-preserving thresholding
NASA Astrophysics Data System (ADS)
Choi, DooSeop; Jung, Hae Kyung; Choi, Hyuk; Kim, Taejeong
2007-09-01
The Moment-Preserving Thresholding technique for digital images has been used in digital image processing for decades, especially in image binarization and image compression. Its main strength lies in that the binary values that the MPT produces as a result, called representative values, are usually unaffected when the signal being thresholded goes through a signal processing operation. The two representative values in MPT together with the threshold value are obtained by solving the system of the preservation equations for the first, second, and third moment. Relying on this robustness of the representative values to various signal processing attacks considered in the watermarking context, this paper proposes a new watermarking scheme for audio signals. The watermark is embedded in the root-sum-square (RSS) of the two representative values of each signal block using the quantization technique. As a result, the RSS values are modified by scaling the signal according to the watermark bit sequence under the constraint of inaudibility relative to the human psycho-acoustic model. We also address and suggest solutions to the problem of synchronization and power scaling attacks. Experimental results show that the proposed scheme maintains high audio quality and robustness to various attacks including MP3 compression, re-sampling, jittering, and, DA/AD conversion.
Advanced optical network architecture for integrated digital avionics
NASA Astrophysics Data System (ADS)
Morgan, D. Reed
1996-12-01
For the first time in the history of avionics, the network designer now has a choice in selecting the media that interconnects the sources and sinks of digital data on aircraft. Electrical designs are already giving way to photonics in application areas where the data rate times distance product is large or where special design requirements such as low weight or EMI considerations are critical. Future digital avionic architectures will increasingly favor the use of photonic interconnects as network data rates of one gigabit/second and higher are needed to support real-time operation of high-speed integrated digital processing. As the cost of optical network building blocks is reduced and as temperature-rugged laser sources are matured, metal interconnects will be forced to retreat to applications spanning shorter and shorter distances. Although the trend is already underway, the widespread use of digital optics will first occur at the system level, where gigabit/second, real-time interconnects between sensors, processors, mass memories and displays separated by a least of few meters will be required. The application of photonic interconnects for inter-printed wiring board signalling across the backplane will eventually find application for gigabit/second applications since signal degradation over copper traces occurs before one gigabit/second and 0.5 meters are reached. For the foreseeable future however, metal interconnects will continue to be used to interconnect devices on printed wiring boards since 5 gigabit/second signals can be sent over metal up to around 15 centimeters. Current-day applications of optical interconnects at the system level are described and a projection of how advanced optical interconnect technology will be driven by the use of high speed integrated digital processing on future aircraft is presented. The recommended advanced network for application in the 2010 time frame is a fiber-based system with a signalling speed of around 2-3 gigabits per second. This switch-based unified network will interconnect sensors, displays, mass memory and controls and displays to computer modules within the processing complex. The characteristics of required building blocks needed for the future are described. These building blocks include the fiber, an optical switch, a laser-based transceiver, blind-mate connectors and an optical backplane.
Design of peptide mimetics to block pro-inflammatory functions of HA fragments.
Hauser-Kawaguchi, Alexandra; Luyt, Leonard G; Turley, Eva
2018-01-31
Hyaluronan is a simple extracellular matrix polysaccharide that actively regulates inflammation in tissue repair and disease processes. The native HA polymer, which is large (>500 kDa), contributes to the maintenance of homeostasis. In remodeling and diseased tissues, polymer size is strikingly polydisperse, ranging from <10 kDa to >500 kDa. In a diseased or stressed tissue context, both smaller HA fragments and high molecular weight HA polymers can acquire pro-inflammatory functions, which result in the activation of multiple receptors, triggering pro-inflammatory signaling to diverse stimuli. Peptide mimics that bind and scavenge HA fragments have been developed, which show efficacy in animal models of inflammation. These studies indicate both that HA fragments are key to driving inflammation and that scavenging these is a viable therapeutic approach to blunting inflammation in disease processes. This mini-review summarizes the peptide-based methods that have been reported to date for blocking HA signaling events as an anti-inflammatory therapeutic approach. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.
GDF10 Is a Signal for Axonal Sprouting and Functional Recovery after Stroke
Li, S; Nie, EH; Yin, Y; Benowitz, LI; Tung, S; Vinters, HV; Bahjat, FR; Stenzel-Poore, MP; Kawaguchi, R; Coppola, G; Carmichael, ST
2016-01-01
Stroke produces a limited process of neural repair. Axonal sprouting in cortex adjacent to the infarct is part of this recovery process, but the signal that initiates axonal sprouting is not known. Growth and Differentiation Factor 10 (GDF10) is induced in peri-infarct neurons in mouse, non-human primate and human. GDF10 promotes axonal outgrowth in vitro in mouse, rat and human neurons through TGFβRI/II signaling. Using pharmacogenetic gain and loss of function studies, GDF10 produces axonal sprouting and enhanced functional recovery after stroke; knocking down GDF10 blocks axonal sprouting and reduces recovery. RNA-seq from peri-infarct cortical neurons indicates that GDF10 downregulates PTEN and upregulates PI3 kinase signaling and induces specific axonal guidance molecules. Unsupervised genome-wide association analysis of the GDF10 transcriptome shows that it is not related to neurodevelopment but may partially overlap with other CNS injury patterns. GDF10 is a stroke-induced signal for axonal sprouting and functional recovery. PMID:26502261
NASA Astrophysics Data System (ADS)
Li, H.; Wong, Wai-Hoi; Zhang, N.; Wang, J.; Uribe, J.; Baghaei, H.; Yokoyama, S.
1999-06-01
Electronics for a prototype high-resolution PET camera with eight position-sensitive detector modules has been developed. Each module has 16 BGO (Bi/sub 4/Ge/sub 3/O/sub 12/) blocks (each block is composed of 49 crystals). The design goals are component and space reduction. The electronics is composed of five parts: front-end analog processing, digital position decoding, fast timing, coincidence processing and master data acquisition. The front-end analog circuit is a zone-based structure (each zone has 3/spl times/3 PMTs). Nine ADCs digitize integration signals of an active zone identified by eight trigger clusters; each cluster is composed of six photomultiplier tubes (PMTs). A trigger corresponding to a gamma ray is sent to a fast timing board to obtain a time-mark, and the nine digitized signals are passed to the position decoding board, where a real block (four PMTs) can be picked out from the zone for position decoding. Lookup tables are used for energy discrimination and to identify the gamma-hit crystal location. The coincidence board opens a 70-ns initial timing window, followed by two 20-ns true/accidental time-mark lookup table windows. The data output from the coincidence board can be acquired either in sinogram mode or in list mode with a Motorola/IRONICS VME-based system.
Graded inhibition of oncogenic Ras-signaling by multivalent Ras-binding domains
2014-01-01
Background Ras is a membrane-associated small G-protein that funnels growth and differentiation signals into downstream signal transduction pathways by cycling between an inactive, GDP-bound and an active, GTP-bound state. Aberrant Ras activity as a result of oncogenic mutations causes de novo cell transformation and promotes tumor growth and progression. Results Here, we describe a novel strategy to block deregulated Ras activity by means of oligomerized cognate protein modules derived from the Ras-binding domain of c-Raf (RBD), which we named MSOR for multivalent scavengers of oncogenic Ras. The introduction of well-characterized mutations into RBD was used to adjust the affinity and hence the blocking potency of MSOR towards activated Ras. MSOR inhibited several oncogenic Ras-stimulated processes including downstream activation of Erk1/2, induction of matrix-degrading enzymes, cell motility and invasiveness in a graded fashion depending on the oligomerization grade and the nature of the individual RBD-modules. The amenability to accurate experimental regulation was further improved by engineering an inducible MSOR-expression system to render the reversal of oncogenic Ras effects controllable. Conclusion MSOR represent a new tool for the experimental and possibly therapeutic selective blockade of oncogenic Ras signals. PMID:24383791
Thura, David; Cos, Ignasi; Trung, Jessica; Cisek, Paul
2014-12-03
Speed-accuracy tradeoffs (SATs) exist in both decision-making and movement control, and are generally studied separately. However, in natural behavior animals are free to adjust the time invested in deciding and moving so as to maximize their reward rate. Here, we investigate whether shared mechanisms exist for SAT adjustment in both decisions and actions. Two monkeys performed a reach decision task in which they watched 15 tokens jump, one every 200 ms, from a central circle to one of two peripheral targets, and had to guess which target would ultimately receive the majority of tokens. The monkeys could decide at any time, and once a target was reached, the remaining token movements accelerated to either 50 ms ("fast" block) or 150 ms ("slow" block). Decisions were generally earlier and less accurate in fast than slow blocks, and in both blocks, the criterion of accuracy decreased over time within each trial. This could be explained by a simple model in which sensory information is combined with a linearly growing urgency signal. Remarkably, the duration of the reaching movements produced after the decision decreased over time in a similar block-dependent manner as the criterion of accuracy estimated by the model. This suggests that SATs for deciding and acting are influenced by a shared urgency/vigor signal. Consistent with this, we observed that the vigor of saccades performed during the decision process was higher in fast than in slow blocks, suggesting the influence of a context-dependent global arousal. Copyright © 2014 the authors 0270-6474/14/3416442-13$15.00/0.
ERIC Educational Resources Information Center
Dade County Public Schools, Miami, FL.
The 135-hour quinmester course covers study of basic radio circuits as applied to vacuum tube radios in six blocks of instruction: orientation; AM receivers with tubes; no signal, audio failure; distortion; weak, noisy signals; and a post-test. Each block is subdivided into several units, and block objectives are outlined. Completion of AC…
Ogawa, Akitoshi; Bordier, Cecile; Macaluso, Emiliano
2013-01-01
The use of naturalistic stimuli to probe sensory functions in the human brain is gaining increasing interest. Previous imaging studies examined brain activity associated with the processing of cinematographic material using both standard “condition-based” designs, as well as “computational” methods based on the extraction of time-varying features of the stimuli (e.g. motion). Here, we exploited both approaches to investigate the neural correlates of complex visual and auditory spatial signals in cinematography. In the first experiment, the participants watched a piece of a commercial movie presented in four blocked conditions: 3D vision with surround sounds (3D-Surround), 3D with monaural sound (3D-Mono), 2D-Surround, and 2D-Mono. In the second experiment, they watched two different segments of the movie both presented continuously in 3D-Surround. The blocked presentation served for standard condition-based analyses, while all datasets were submitted to computation-based analyses. The latter assessed where activity co-varied with visual disparity signals and the complexity of auditory multi-sources signals. The blocked analyses associated 3D viewing with the activation of the dorsal and lateral occipital cortex and superior parietal lobule, while the surround sounds activated the superior and middle temporal gyri (S/MTG). The computation-based analyses revealed the effects of absolute disparity in dorsal occipital and posterior parietal cortices and of disparity gradients in the posterior middle temporal gyrus plus the inferior frontal gyrus. The complexity of the surround sounds was associated with activity in specific sub-regions of S/MTG, even after accounting for changes of sound intensity. These results demonstrate that the processing of naturalistic audio-visual signals entails an extensive set of visual and auditory areas, and that computation-based analyses can track the contribution of complex spatial aspects characterizing such life-like stimuli. PMID:24194828
Ogawa, Akitoshi; Bordier, Cecile; Macaluso, Emiliano
2013-01-01
The use of naturalistic stimuli to probe sensory functions in the human brain is gaining increasing interest. Previous imaging studies examined brain activity associated with the processing of cinematographic material using both standard "condition-based" designs, as well as "computational" methods based on the extraction of time-varying features of the stimuli (e.g. motion). Here, we exploited both approaches to investigate the neural correlates of complex visual and auditory spatial signals in cinematography. In the first experiment, the participants watched a piece of a commercial movie presented in four blocked conditions: 3D vision with surround sounds (3D-Surround), 3D with monaural sound (3D-Mono), 2D-Surround, and 2D-Mono. In the second experiment, they watched two different segments of the movie both presented continuously in 3D-Surround. The blocked presentation served for standard condition-based analyses, while all datasets were submitted to computation-based analyses. The latter assessed where activity co-varied with visual disparity signals and the complexity of auditory multi-sources signals. The blocked analyses associated 3D viewing with the activation of the dorsal and lateral occipital cortex and superior parietal lobule, while the surround sounds activated the superior and middle temporal gyri (S/MTG). The computation-based analyses revealed the effects of absolute disparity in dorsal occipital and posterior parietal cortices and of disparity gradients in the posterior middle temporal gyrus plus the inferior frontal gyrus. The complexity of the surround sounds was associated with activity in specific sub-regions of S/MTG, even after accounting for changes of sound intensity. These results demonstrate that the processing of naturalistic audio-visual signals entails an extensive set of visual and auditory areas, and that computation-based analyses can track the contribution of complex spatial aspects characterizing such life-like stimuli.
NASA Astrophysics Data System (ADS)
Krasilenko, Vladimir G.; Bardachenko, Vitaliy F.; Nikolsky, Alexander I.; Lazarev, Alexander A.
2007-04-01
In the paper we show that the biologically motivated conception of the use of time-pulse encoding gives the row of advantages (single methodological basis, universality, simplicity of tuning, training and programming et al) at creation and designing of sensor systems with parallel input-output and processing, 2D-structures of hybrid and neuro-fuzzy neurocomputers of next generations. We show principles of construction of programmable relational optoelectronic time-pulse coded processors, continuous logic, order logic and temporal waves processes, that lie in basis of the creation. We consider structure that executes extraction of analog signal of the set grade (order), sorting of analog and time-pulse coded variables. We offer optoelectronic realization of such base relational elements of order logic, which consists of time-pulse coded phototransformers (pulse-width and pulse-phase modulators) with direct and complementary outputs, sorting network on logical elements and programmable commutations blocks. We make estimations of basic technical parameters of such base devices and processors on their basis by simulation and experimental research: power of optical input signals - 0.200-20 μW, processing time - microseconds, supply voltage - 1.5-10 V, consumption power - hundreds of microwatts per element, extended functional possibilities, training possibilities. We discuss some aspects of possible rules and principles of training and programmable tuning on the required function, relational operation and realization of hardware blocks for modifications of such processors. We show as on the basis of such quasiuniversal hardware simple block and flexible programmable tuning it is possible to create sorting machines, neural networks and hybrid data-processing systems with the untraditional numerical systems and pictures operands.
Pitts, Natalie L; Schulz, Hanna M; Oatman, Stephanie R; Mykles, Donald L
2017-12-01
Molting is induced in decapod crustaceans via multiple leg autotomy (MLA) or eyestalk ablation (ESA). MLA removes five or more walking legs, which are regenerated and become functional appendages at ecdysis. ESA eliminates the primary source of molt-inhibiting hormone (MIH) and crustacean hyperglycemic hormone (CHH), which suppress the production of molting hormones (ecdysteroids) from the molting gland or Y-organ (YO). Both MLA and ESA are effective methods for molt induction in Gecarcinus lateralis. However, some G. lateralis individuals are refractory to MLA, as they fail to complete ecdysis by 12weeks post-MLA; these animals are in the "blocked" condition. Quantitative polymerase chain reaction was used to quantify mRNA levels of neuropeptide and mechanistic target of rapamycin (mTOR) signaling genes in YO, eyestalk ganglia (ESG), thoracic ganglion (TG), and brain of intact and blocked animals. Six of the seven neuropeptide signaling genes, three of four mTOR signaling genes, and Gl-elongation factor 2 (EF2) mRNA levels were significantly higher in the ESG of blocked animals. Gl-MIH and Gl-CHH mRNA levels were higher in the TG and brain of blocked animals and levels increased in both control and blocked animals in response to ESA. By contrast, mRNA levels of Gl-EF2 and five of the 10 MIH signaling pathway genes in the YO were two to four orders of magnitude higher in blocked animals compared to controls. These data suggest that increased MIH and CHH synthesis in the ESG contributes to the prevention of molt induction by MLA in blocked animals. The up-regulation of MIH signaling genes in the YO of blocked animals suggests that the YO is more sensitive to MIH produced in the ESG, as well as MIH produced in brain and TG of ESA animals. Both the up-regulation of MIH signaling genes in the YO and of Gl-MIH and Gl-CHH in the ESG, TG, and brain appear to contribute to some G. lateralis individuals being refractory to MLA and ESA. Copyright © 2017 Elsevier Inc. All rights reserved.
Femtosecond Carrier Processes in Compound Semiconductors and Real Time Signal Processing
1993-03-10
Blocks in Real Schur Form" ................... 179 5. "The Periodic Schur Decomposition. Algorithms and A p p lication s...existence of short period superlattices (confined LO GaAs and AlAs vibrations) on all samples produced with this method. The degret of deposition zone...small amount of zone intermixing occurs in the spatially separated growth mode (see 1 Figure 1b), the short period superlattices have graded interfaces
Cell Aggregation-induced FGF8 Elevation Is Essential for P19 Cell Neural Differentiation
Wang, Chen; Xia, Caihong; Bian, Wei; Liu, Li; Lin, Wei; Chen, Ye-Guang; Ang, Siew-Lan
2006-01-01
FGF8, a member of the fibroblast growth factor (FGF) family, has been shown to play important roles in different developing systems. Mouse embryonic carcinoma P19 cells could be induced by retinoic acid (RA) to differentiate into neuroectodermal cell lineages, and this process is cell aggregation dependent. In this report, we show that FGF8 expression is transiently up-regulated upon P19 cell aggregation, and the aggregation-dependent FGF8 elevation is pluripotent stem cell related. Overexpressing FGF8 promotes RA-induced monolayer P19 cell neural differentiation. Inhibition of FGF8 expression by RNA interference or blocking FGF signaling by the FGF receptor inhibitor, SU5402, attenuates neural differentiation of the P19 cell. Blocking the bone morphogenetic protein (BMP) pathway by overexpressing Smad6 in P19 cells, we also show that FGF signaling plays a BMP inhibition–independent role in P19 cell neural differentiation. PMID:16641368
Barquilla, Antonio; Lamberto, Ilaria; Noberini, Roberta; Heynen-Genel, Susanne; Brill, Laurence M.; Pasquale, Elena B.
2016-01-01
The EphA2 receptor tyrosine kinase plays key roles in tissue homeostasis and disease processes such as cancer, pathological angiogenesis, and inflammation through two distinct signaling mechanisms. EphA2 “canonical” signaling involves ephrin-A ligand binding, tyrosine autophosphorylation, and kinase activity; EphA2 “noncanonical” signaling involves phosphorylation of serine 897 (S897) by AKT and RSK kinases. To identify small molecules counteracting EphA2 canonical signaling, we developed a high-content screening platform measuring inhibition of ephrin-A1–induced PC3 prostate cancer cell retraction. Surprisingly, most hits from a screened collection of pharmacologically active compounds are agents that elevate intracellular cAMP by activating G protein–coupled receptors such as the β2-adrenoceptor. We found that cAMP promotes phosphorylation of S897 by protein kinase A (PKA) as well as increases the phosphorylation of several nearby serine/threonine residues, which constitute a phosphorylation hotspot. Whereas EphA2 canonical and noncanonical signaling have been viewed as mutually exclusive, we show that S897 phosphorylation by PKA can coexist with EphA2 tyrosine phosphorylation and block cell retraction induced by EphA2 kinase activity. Our findings reveal a novel paradigm in EphA2 function involving the interplay of canonical and noncanonical signaling and highlight the ability of the β2-adrenoceptor/cAMP/PKA axis to rewire EphA2 signaling in a subset of cancer cells. PMID:27385333
Zhang, Hong; Ren, Lei; Kong, Vic; Giles, William; Zhang, You; Jin, Jian-Yue
2016-01-01
A preobject grid can reduce and correct scatter in cone beam computed tomography (CBCT). However, half of the signal in each projection is blocked by the grid. A synchronized moving grid (SMOG) has been proposed to acquire two complimentary projections at each gantry position and merge them into one complete projection. That approach, however, suffers from increased scanning time and the technical difficulty of accurately merging the two projections per gantry angle. Herein, the authors present a new SMOG approach which acquires a single projection per gantry angle, with complimentary grid patterns for any two adjacent projections, and use an interprojection sensor fusion (IPSF) technique to estimate the blocked signal in each projection. The method may have the additional benefit of reduced imaging dose due to the grid blocking half of the incident radiation. The IPSF considers multiple paired observations from two adjacent gantry angles as approximations of the blocked signal and uses a weighted least square regression of these observations to finally determine the blocked signal. The method was first tested with a simulated SMOG on a head phantom. The signal to noise ratio (SNR), which represents the difference of the recovered CBCT image to the original image without the SMOG, was used to evaluate the ability of the IPSF in recovering the missing signal. The IPSF approach was then tested using a Catphan phantom on a prototype SMOG assembly installed in a bench top CBCT system. In the simulated SMOG experiment, the SNRs were increased from 15.1 and 12.7 dB to 35.6 and 28.9 dB comparing with a conventional interpolation method (inpainting method) for a projection and the reconstructed 3D image, respectively, suggesting that IPSF successfully recovered most of blocked signal. In the prototype SMOG experiment, the authors have successfully reconstructed a CBCT image using the IPSF-SMOG approach. The detailed geometric features in the Catphan phantom were mostly recovered according to visual evaluation. The scatter related artifacts, such as cupping artifacts, were almost completely removed. The IPSF-SMOG is promising in reducing scatter artifacts and improving image quality while reducing radiation dose.
Protective Mechanism of STAT3-siRNA on Cerebral Ischemia Injury
NASA Astrophysics Data System (ADS)
He, Jinting; Yang, Le; Liang, Wenzhao
2018-01-01
Nerve cells in ischemic brain injury will occur a series of complex signal transduction pathway changes and produce the corresponding biological function, thus affecting the central nervous system functionally different cells in the ischemic brain injury metabolism, division, Differentiation and death process, while changes in signal pathways also play an important role in the repair process of the post-ischemic nervous system. JAK/STAT pathway and vascular lesions have some relevance, but its exact mechanism after cerebral ischemia is not yet fully understood. This study is intended to further explore the JAK / STAT pathway in the functional site of STAT3 in neuronal ischemia Hypoxic injury and related molecular mechanisms, targeting these targets design intervention strategies to block the signal pathway, in order to provide a theoretical basis for the treatment of ischemic brain damage in this pathway.
Zhou, Xiao-Yi; Xu, Xi-Ming; Wu, Sui-Yi; Zhang, Zi-Cheng; Wang, Fei; Yang, Yi-Lin; Li, Ming; Wei, Xian-Zhao
2018-05-01
Low-intensity pulsed ultrasound (LIPUS) has been found to accelerate the healing process of spinal fusion via a process closely related to osteoblast differentiation and migration. Sonic hedgehog (Shh) signaling plays an important role in development and homeostasis, including a critical function in bone formation. However, its role in spinal fusion during LIPUS treatment is still unknown. This study showed that LIPUS treatment after spinal fusion surgery increased bone formation. The increased bone mass under LIPUS treatment appeared to result from the increased migration and proliferation of osteoblasts, resulting from upregulation of the Shh signaling pathway. In contrast, inhibition of Shh reduced the migratory and proliferative ability of osteoblast-like MG63 cells and blocked the efficacy of LIPUS treatment. Copyright © 2018 Elsevier Inc. All rights reserved.
Mitochondrial Energy and Redox Signaling in Plants
Schwarzländer, Markus
2013-01-01
Abstract Significance: For a plant to grow and develop, energy and appropriate building blocks are a fundamental requirement. Mitochondrial respiration is a vital source for both. The delicate redox processes that make up respiration are affected by the plant's changing environment. Therefore, mitochondrial regulation is critically important to maintain cellular homeostasis. This involves sensing signals from changes in mitochondrial physiology, transducing this information, and mounting tailored responses, by either adjusting mitochondrial and cellular functions directly or reprogramming gene expression. Recent Advances: Retrograde (RTG) signaling, by which mitochondrial signals control nuclear gene expression, has been a field of very active research in recent years. Nevertheless, no mitochondrial RTG-signaling pathway is yet understood in plants. This review summarizes recent advances toward elucidating redox processes and other bioenergetic factors as a part of RTG signaling of plant mitochondria. Critical Issues: Novel insights into mitochondrial physiology and redox-regulation provide a framework of upstream signaling. On the other end, downstream responses to modified mitochondrial function have become available, including transcriptomic data and mitochondrial phenotypes, revealing processes in the plant that are under mitochondrial control. Future Directions: Drawing parallels to chloroplast signaling and mitochondrial signaling in animal systems allows to bridge gaps in the current understanding and to deduce promising directions for future research. It is proposed that targeted usage of new technical approaches, such as quantitative in vivo imaging, will provide novel leverage to the dissection of plant mitochondrial signaling. Antioxid. Redox Signal. 18, 2122–2144. PMID:23234467
ERK activation is required for CCK-mediated pancreatic adaptive growth in mice
Holtz, Bryan J.; Lodewyk, Kevin B.; Sebolt-Leopold, Judith S.; Ernst, Stephen A.
2014-01-01
High levels of cholecystokinin (CCK) can stimulate pancreatic adaptive growth in which mature acinar cells divide, leading to enhanced pancreatic mass with parallel increases in protein, DNA, RNA, and digestive enzyme content. Prolonged release of CCK can be induced by feeding trypsin inhibitor (TI) to disrupt normal feedback control. This leads to exocrine growth in a CCK-dependent manner. The extracellular signal-related kinase (ERK) pathway regulates many proliferative processes in various tissues and disease models. The aim of this study was to evaluate the role of ERK signaling in pancreatic adaptive growth using the MEK inhibitors PD-0325901 and trametinib (GSK-1120212). It was determined that PD-0325901 given two times daily by gavage or mixed into powdered chow was an effective and specific inhibitor of ERK signaling in vivo. TI-containing chow led to a robust increase in pancreatic mass, protein, DNA, and RNA content. This pancreatic adaptive growth was blocked in mice fed chow containing the MEK inhibitors. PD-0325901 blocked TI-induced ERK-regulated early response genes, cell-cycle proteins, and mitogenesis by acinar cells. It was determined that ERK signaling is necessary for the initiation of pancreatic adaptive growth but not necessary to maintain it. PD-0325901 blocked adaptive growth when given before cell-cycle initiation but not after mitogenesis had been established. Furthermore, GSK-1120212, a chemically distinct inhibitor of the ERK pathway that is now approved for clinical use, inhibited growth similar to PD-0325901. These data demonstrate that the ERK pathway is required for CCK-stimulated pancreatic adaptive growth. PMID:25104499
Boubaker, Moez Ben; Picard, Donald; Duchesne, Carl; Tessier, Jayson; Alamdari, Houshang; Fafard, Mario
2018-05-17
This paper reports on the application of an acousto-ultrasonic (AU) scheme for the inspection of industrial-size carbon anode blocks used in the production of primary aluminium by the Hall-Héroult process. A frequency-modulated wave is used to excite the anode blocks at multiple points. The collected attenuated AU signals are decomposed using the Discrete Wavelet Transform (DTW) after which vectors of features are calculated. Principal Component Analysis (PCA) is utilized to cluster the AU responses of the anodes. The approach allows locating cracks in the blocks and the AU features were found sensitive to crack severity. The results are validated using images collected after cutting some anodes. Copyright © 2018 Elsevier B.V. All rights reserved.
Optomotor-blind negatively regulates Drosophila eye development by blocking Jak/STAT signaling.
Tsai, Yu-Chen; Grimm, Stefan; Chao, Ju-Lan; Wang, Shih-Chin; Hofmeyer, Kerstin; Shen, Jie; Eichinger, Fred; Michalopoulou, Theoni; Yao, Chi-Kuang; Chang, Chih-Hsuan; Lin, Shih-Han; Sun, Y Henry; Pflugfelder, Gert O
2015-01-01
Organ formation requires a delicate balance of positive and negative regulators. In Drosophila eye development, wingless (wg) is expressed at the lateral margins of the eye disc and serves to block retinal development. The T-box gene optomotor-blind (omb) is expressed in a similar pattern and is regulated by Wg. Omb mediates part of Wg activity in blocking eye development. Omb exerts its function primarily by blocking cell proliferation. These effects occur predominantly in the ventral margin. Our results suggest that the primary effect of Omb is the blocking of Jak/STAT signaling by repressing transcription of upd which encodes the Jak receptor ligand Unpaired.
NASA Astrophysics Data System (ADS)
Danilin, A. I.; Neverov, V. V.; Danilin, S. A.; Shimanov, A. A.; Tsapkova, A. B.
2018-01-01
The article describes a noncontact operational control method based on the processing of a microwave signal reflected from the controlled teeth of the wheel. In this paper describes the influence of wear patterns on the characteristic information parameters of the analyzed signals. The block diagram in section 3 shows the experimental system for monitoring the operating state of the gear wheels of the steam compressor torque multiplier. The design of the primary converter is briefly described.
Seismic anisotropy in central North Anatolian Fault Zone and its implications on crustal deformation
NASA Astrophysics Data System (ADS)
Licciardi, A.; Eken, T.; Taymaz, T.; Piana Agostinetti, N.; Yolsal-Çevikbilen, S.
2018-04-01
We investigate the crustal seismic structure and anisotropy around the central portion of the North Anatolian Fault Zone, a major plate boundary, using receiver function analysis. The characterization of crustal seismic anisotropy plays a key role in our understanding of present and past deformation processes at plate boundaries. The development of seismic anisotropy in the crust arises from the response of the rocks to complicated deformation regimes induced by plate interaction. Through the analysis of azimuthally-varying signals of teleseismic receiver functions, we map the anisotropic properties of the crust as a function of depth, by employing the harmonic decomposition technique. Although the Moho is located at a depth of about 40 km, with no major offset across the area, our results show a clear asymmetric distribution of crustal properties between the northern and southern blocks, divided by the North Anatolian Fault Zone. Heterogeneous and strongly anisotropic crust is present in the southern block, where complex intra-crustal signals are the results of strong deformation. In the north, a simpler and weakly anisotropic crust is typically observed. The strongest anisotropic signal is located in the first 15 km of the crust and is widespread in the southern block. Stations located on top of the main active faults in the area indicate the highest amplitudes, together with fault-parallel strikes of the fast plane of anisotropy. We interpret the origin of this signal as due to structure-induced anisotropy, and roughly determine its depth extent up to 15-20 km for these stations. Away from the faults, we suggest the contribution of previously documented uplifted basement blocks to explain the observed anisotropy at upper and middle crustal depths. Finally, we interpret coherent NE-SW orientations below the Moho as a result of frozen-in anisotropy in the upper mantle, as suggested by previous studies.
NASA Technical Reports Server (NTRS)
Mulavara, Ajitkumar; Fiedler, Matthew; Kofman, Igor; Peters, Brian; Wood, Scott; Serrador, Jorge; Cohen, Helen; Reschke, Millard; Bloomberg, Jacob
2010-01-01
Stochastic resonance (SR) is a mechanism by which noise can assist and enhance the response of neural systems to relevant sensory signals. Application of imperceptible SR noise coupled with sensory input through the proprioceptive, visual, or vestibular sensory systems has been shown to improve motor function. Specifically, studies have shown that that vestibular electrical stimulation by imperceptible stochastic noise, when applied to normal young and elderly subjects, significantly improved their ocular stabilization reflexes in response to whole-body tilt as well as balance performance during postural disturbances. The goal of this study was to optimize the characteristics of the stochastic vestibular signals for balance performance during standing on an unstable surface. Subjects performed a standardized balance task of standing on a block of 10 cm thick medium density foam with their eyes closed for a total of 40 seconds. Stochastic electrical stimulation was applied to the vestibular system through electrodes placed over the mastoid process behind the ears during the last 20 seconds of the test period. A custom built constant current stimulator with subject isolation delivered the stimulus. Stimulation signals were generated with frequencies in the bandwidth of 1-2 Hz and 0.01-30 Hz. Amplitude of the signals were varied in the range of 0- +/-700 micro amperes with the RMS of the signal increased by 30 micro amperes for each 100 micro amperes increase in the current range. Balance performance was measured using a force plate under the foam block and inertial motion sensors placed on the torso and head segments. Preliminary results indicate that balance performance is improved in the range of 10-25% compared to no stimulation conditions. Subjects improved their performance consistently across the blocks of stimulation. Further the signal amplitude at which the performance was maximized was different in the two frequency ranges. Optimization of the frequency and amplitude of the signal characteristics of the stochastic noise signals on maximizing balance performance will have a significant impact in its development as a unique system to aid recovery of function in astronauts after long duration space flight or for people with balance disorders.
Grieder, Taryn E; Sellings, Laurie H; Vargas-Perez, Hector; Ting-A-Kee, Ryan; Siu, Eric C; Tyndale, Rachel F; van der Kooy, Derek
2010-01-01
The mesolimbic dopamine (DA) system is implicated in the processing of the positive reinforcing effect of all drugs of abuse, including nicotine. It has been suggested that the dopaminergic system is also involved in the aversive motivational response to drug withdrawal, particularly for opiates, however, the role for dopaminergic signaling in the processing of the negative motivational properties of nicotine withdrawal is largely unknown. We hypothesized that signaling at dopaminergic receptors mediates chronic nicotine withdrawal aversions and that dopaminergic signaling would differentially mediate acute vs dependent nicotine motivation. We report that nicotine-dependent rats and mice showed conditioned place aversions to an environment paired with abstinence from chronic nicotine that were blocked by the DA receptor antagonist α-flupenthixol (α-flu) and in DA D2 receptor knockout mice. Conversely, α-flu pretreatment had no effect on preferences for an environment paired with abstinence from acute nicotine. Taken together, these results suggest that dopaminergic signaling is necessary for the opponent motivational response to nicotine in dependent, but not non-dependent, rodents. Further, signaling at the DA D2 receptor is critical in mediating withdrawal aversions in nicotine-dependent animals. We suggest that the alleviation of nicotine withdrawal primarily may be driving nicotine motivation in dependent animals. PMID:20032966
Bmp signaling mediates endoderm pouch morphogenesis by regulating Fgf signaling in zebrafish.
Lovely, C Ben; Swartz, Mary E; McCarthy, Neil; Norrie, Jacqueline L; Eberhart, Johann K
2016-06-01
The endodermal pouches are a series of reiterated structures that segment the pharyngeal arches and help pattern the vertebrate face. Multiple pathways regulate the complex process of endodermal development, including the Bone morphogenetic protein (Bmp) pathway. However, the role of Bmp signaling in pouch morphogenesis is poorly understood. Using genetic and chemical inhibitor approaches, we show that pouch morphogenesis requires Bmp signaling from 10-18 h post-fertilization, immediately following gastrulation. Blocking Bmp signaling during this window results in morphological defects to the pouches and craniofacial skeleton. Using genetic chimeras we show that Bmp signals directly to the endoderm for proper morphogenesis. Time-lapse imaging and analysis of reporter transgenics show that Bmp signaling is necessary for pouch outpocketing via the Fibroblast growth factor (Fgf) pathway. Double loss-of-function analyses demonstrate that Bmp and Fgf signaling interact synergistically in craniofacial development. Collectively, our analyses shed light on the tissue and signaling interactions that regulate development of the vertebrate face. © 2016. Published by The Company of Biologists Ltd.
Bmp signaling mediates endoderm pouch morphogenesis by regulating Fgf signaling in zebrafish
Swartz, Mary E.; McCarthy, Neil; Norrie, Jacqueline L.; Eberhart, Johann K.
2016-01-01
The endodermal pouches are a series of reiterated structures that segment the pharyngeal arches and help pattern the vertebrate face. Multiple pathways regulate the complex process of endodermal development, including the Bone morphogenetic protein (Bmp) pathway. However, the role of Bmp signaling in pouch morphogenesis is poorly understood. Using genetic and chemical inhibitor approaches, we show that pouch morphogenesis requires Bmp signaling from 10-18 h post-fertilization, immediately following gastrulation. Blocking Bmp signaling during this window results in morphological defects to the pouches and craniofacial skeleton. Using genetic chimeras we show that Bmp signals directly to the endoderm for proper morphogenesis. Time-lapse imaging and analysis of reporter transgenics show that Bmp signaling is necessary for pouch outpocketing via the Fibroblast growth factor (Fgf) pathway. Double loss-of-function analyses demonstrate that Bmp and Fgf signaling interact synergistically in craniofacial development. Collectively, our analyses shed light on the tissue and signaling interactions that regulate development of the vertebrate face. PMID:27122171
Ramachandran, Kapil V.; Margolis, Seth S.
2017-01-01
In the nervous system, rapidly occurring processes such as neuronal transmission and calcium signaling are affected by short-term inhibition of proteasome function. It remains unclear how proteasomes can acutely regulate such processes, as this is inconsistent with their canonical role in proteostasis. Here, we made the discovery of a mammalian nervous system-specific membrane proteasome complex that directly and rapidly modulates neuronal function by degrading intracellular proteins into extracellular peptides that can stimulate neuronal signaling. This proteasome complex is tightly associated with neuronal plasma membranes, exposed to the extracellular space, and catalytically active. Selective inhibition of this membrane proteasome complex by a cell-impermeable proteasome inhibitor blocked extracellular peptide production and attenuated neuronal activity-induced calcium signaling. Moreover, membrane proteasome-derived peptides are sufficient to induce neuronal calcium signaling. Our discoveries challenge the prevailing notion that proteasomes primarily function to maintain proteostasis, and highlight a form of neuronal communication through a membrane proteasome complex. PMID:28287632
Wang, Zhiguo; Ullah, Zakir; Gao, Mengqin; Zhang, Dan; Zhang, Yiqi; Gao, Hong; Zhang, Yanpeng
2015-01-01
Optical transistor is a device used to amplify and switch optical signals. Many researchers focus on replacing current computer components with optical equivalents, resulting in an optical digital computer system processing binary data. Electronic transistor is the fundamental building block of modern electronic devices. To replace electronic components with optical ones, an equivalent optical transistor is required. Here we compare the behavior of an optical transistor with the reflection from a photonic band gap structure in an electromagnetically induced transparency medium. A control signal is used to modulate the photonic band gap structure. Power variation of the control signal is used to provide an analogy between the reflection behavior caused by modulating the photonic band gap structure and the shifting of Q-point (Operation point) as well as amplification function of optical transistor. By means of the control signal, the switching function of optical transistor has also been realized. Such experimental schemes could have potential applications in making optical diode and optical transistor used in quantum information processing. PMID:26349444
Adaptive Wiener filtering for improved acquisition of distortion product otoacoustic emissions.
Ozdamar, O; Delgado, R E; Rahman, S; Lopez, C
1998-01-01
An innovative acoustic noise canceling method using adaptive Wiener filtering (AWF) was developed for improved acquisition of distortion product otoacoustic emissions (DPOAEs). The system used one microphone placed in the test ear for the primary signal. Noise reference signals were obtained from three different sources: (a) pre-stimulus response from the test ear microphone, (b) post-stimulus response from a microphone placed near the head of the subject and (c) post-stimulus response obtained from a microphone placed in the subject's nontest ear. In order to improve spectral estimation, block averaging of a different number of single sweep responses was used. DPOAE data were obtained from 11 ears of healthy newborns in a well-baby nursery of a hospital under typical noise conditions. Simultaneously obtained recordings from all three microphones were digitized, stored and processed off-line to evaluate the effects of AWF with respect to DPOAE detection and signal-to-noise ratio (SNR) improvement. Results show that compared to standard DPOAE processing, AWF improved signal detection and improved SNR.
NASA Astrophysics Data System (ADS)
Wang, Zhiguo; Ullah, Zakir; Gao, Mengqin; Zhang, Dan; Zhang, Yiqi; Gao, Hong; Zhang, Yanpeng
2015-09-01
Optical transistor is a device used to amplify and switch optical signals. Many researchers focus on replacing current computer components with optical equivalents, resulting in an optical digital computer system processing binary data. Electronic transistor is the fundamental building block of modern electronic devices. To replace electronic components with optical ones, an equivalent optical transistor is required. Here we compare the behavior of an optical transistor with the reflection from a photonic band gap structure in an electromagnetically induced transparency medium. A control signal is used to modulate the photonic band gap structure. Power variation of the control signal is used to provide an analogy between the reflection behavior caused by modulating the photonic band gap structure and the shifting of Q-point (Operation point) as well as amplification function of optical transistor. By means of the control signal, the switching function of optical transistor has also been realized. Such experimental schemes could have potential applications in making optical diode and optical transistor used in quantum information processing.
Probabilistic switching circuits in DNA
Wilhelm, Daniel; Bruck, Jehoshua
2018-01-01
A natural feature of molecular systems is their inherent stochastic behavior. A fundamental challenge related to the programming of molecular information processing systems is to develop a circuit architecture that controls the stochastic states of individual molecular events. Here we present a systematic implementation of probabilistic switching circuits, using DNA strand displacement reactions. Exploiting the intrinsic stochasticity of molecular interactions, we developed a simple, unbiased DNA switch: An input signal strand binds to the switch and releases an output signal strand with probability one-half. Using this unbiased switch as a molecular building block, we designed DNA circuits that convert an input signal to an output signal with any desired probability. Further, this probability can be switched between 2n different values by simply varying the presence or absence of n distinct DNA molecules. We demonstrated several DNA circuits that have multiple layers and feedback, including a circuit that converts an input strand to an output strand with eight different probabilities, controlled by the combination of three DNA molecules. These circuits combine the advantages of digital and analog computation: They allow a small number of distinct input molecules to control a diverse signal range of output molecules, while keeping the inputs robust to noise and the outputs at precise values. Moreover, arbitrarily complex circuit behaviors can be implemented with just a single type of molecular building block. PMID:29339484
Stimulus Characteristics for Vestibular Stochastic Resonance to Improve Balance Function
NASA Technical Reports Server (NTRS)
Mulavara, Ajitkumar; Fiedler, Matthew; Kofman, Igor; Peters, Brian; Wood, Scott; Serrado, Jorge; Cohen, Helen; Reschke, Millard; Bloomberg, Jacob
2010-01-01
Stochastic resonance (SR) is a mechanism by which noise can enhance the response of neural systems to relevant sensory signals. Studies have shown that imperceptible stochastic vestibular electrical stimulation, when applied to normal young and elderly subjects, significantly improved their ocular stabilization reflexes in response to whole-body tilt as well as balance performance during postural disturbances. The goal of this study was to optimize the amplitude characteristics of the stochastic vestibular signals for balance performance during standing on an unstable surface. Subjects performed a standard balance task of standing on a block of foam with their eyes closed. Bipolar stochastic electrical stimulation was applied to the vestibular system using constant current stimulation through electrodes placed over the mastoid process behind the ears. Amplitude of the signals varied in the range of 0-700 microamperes. Balance performance was measured using a force plate under the foam block, and inertial motion sensors were placed on the torso and head. Balance performance with stimulation was significantly greater (10%-25%) than with no stimulation. The signal amplitude at which performance was maximized was in the range of 100-300 microamperes. Optimization of the amplitude of the stochastic signals for maximizing balance performance will have a significant impact on development of vestibular SR as a unique system to aid recovery of function in astronauts after long-duration space flight or in patients with balance disorders.
Yildirim, Özal
2018-05-01
Long-short term memory networks (LSTMs), which have recently emerged in sequential data analysis, are the most widely used type of recurrent neural networks (RNNs) architecture. Progress on the topic of deep learning includes successful adaptations of deep versions of these architectures. In this study, a new model for deep bidirectional LSTM network-based wavelet sequences called DBLSTM-WS was proposed for classifying electrocardiogram (ECG) signals. For this purpose, a new wavelet-based layer is implemented to generate ECG signal sequences. The ECG signals were decomposed into frequency sub-bands at different scales in this layer. These sub-bands are used as sequences for the input of LSTM networks. New network models that include unidirectional (ULSTM) and bidirectional (BLSTM) structures are designed for performance comparisons. Experimental studies have been performed for five different types of heartbeats obtained from the MIT-BIH arrhythmia database. These five types are Normal Sinus Rhythm (NSR), Ventricular Premature Contraction (VPC), Paced Beat (PB), Left Bundle Branch Block (LBBB), and Right Bundle Branch Block (RBBB). The results show that the DBLSTM-WS model gives a high recognition performance of 99.39%. It has been observed that the wavelet-based layer proposed in the study significantly improves the recognition performance of conventional networks. This proposed network structure is an important approach that can be applied to similar signal processing problems. Copyright © 2018 Elsevier Ltd. All rights reserved.
Talanow, Tobias; Kasparbauer, Anna-Maria; Steffens, Maria; Meyhöfer, Inga; Weber, Bernd; Smyrnis, Nikolaos; Ettinger, Ulrich
2016-08-01
The antisaccade task is a prominent tool to investigate the response inhibition component of cognitive control. Recent theoretical accounts explain performance in terms of parallel programming of exogenous and endogenous saccades, linked to the horse race metaphor. Previous studies have tested the hypothesis of competing saccade signals at the behavioral level by selectively slowing the programming of endogenous or exogenous processes e.g. by manipulating the probability of antisaccades in an experimental block. To gain a better understanding of inhibitory control processes in parallel saccade programming, we analyzed task-related eye movements and blood oxygenation level dependent (BOLD) responses obtained using functional magnetic resonance imaging (fMRI) at 3T from 16 healthy participants in a mixed antisaccade and prosaccade task. The frequency of antisaccade trials was manipulated across blocks of high (75%) and low (25%) antisaccade frequency. In blocks with high antisaccade frequency, antisaccade latencies were shorter and error rates lower whilst prosaccade latencies were longer and error rates were higher. At the level of BOLD, activations in the task-related saccade network (left inferior parietal lobe, right inferior parietal sulcus, left precentral gyrus reaching into left middle frontal gyrus and inferior frontal junction) and deactivations in components of the default mode network (bilateral temporal cortex, ventromedial prefrontal cortex) compensated increased cognitive control demands. These findings illustrate context dependent mechanisms underlying the coordination of competing decision signals in volitional gaze control. Copyright © 2016 Elsevier Inc. All rights reserved.
Optomotor-Blind Negatively Regulates Drosophila Eye Development by Blocking Jak/STAT Signaling
Tsai, Yu-Chen; Grimm, Stefan; Chao, Ju-Lan; Wang, Shih-Chin; Hofmeyer, Kerstin; Shen, Jie; Eichinger, Fred; Michalopoulou, Theoni; Yao, Chi-Kuang; Chang, Chih-Hsuan; Lin, Shih-Han; Sun, Y. Henry; Pflugfelder, Gert O.
2015-01-01
Organ formation requires a delicate balance of positive and negative regulators. In Drosophila eye development, wingless (wg) is expressed at the lateral margins of the eye disc and serves to block retinal development. The T-box gene optomotor-blind (omb) is expressed in a similar pattern and is regulated by Wg. Omb mediates part of Wg activity in blocking eye development. Omb exerts its function primarily by blocking cell proliferation. These effects occur predominantly in the ventral margin. Our results suggest that the primary effect of Omb is the blocking of Jak/STAT signaling by repressing transcription of upd which encodes the Jak receptor ligand Unpaired. PMID:25781970
Blocking Losses With a Photon Counter
NASA Technical Reports Server (NTRS)
Moision, Burce E.; Piazzolla, Sabino
2012-01-01
It was not known how to assess accurately losses in a communications link due to photodetector blocking, a phenomenon wherein a detector is rendered inactive for a short time after the detection of a photon. When used to detect a communications signal, blocking leads to losses relative to an ideal detector, which may be measured as a reduction in the communications rate for a given received signal power, or an increase in the signal power required to support the same communications rate. This work involved characterizing blocking losses for single detectors and arrays of detectors. Blocking may be mitigated by spreading the signal intensity over an array of detectors, reducing the count rate on any one detector. A simple approximation was made to the blocking loss as a function of the probability that a detector is unblocked at a given time, essentially treating the blocking probability as a scaling of the detection efficiency. An exact statistical characterization was derived for a single detector, and an approximation for multiple detectors. This allowed derivation of several accurate approximations to the loss. Methods were also derived to account for a rise time in recovery, and non-uniform illumination due to diffraction and atmospheric distortion of the phase front. It was assumed that the communications signal is intensity modulated and received by an array of photon-counting photodetectors. For the purpose of this analysis, it was assumed that the detectors are ideal, in that they produce a signal that allows one to reproduce the arrival times of electrons, produced either as photoelectrons or from dark noise, exactly. For single detectors, the performance of the maximum-likelihood (ML) receiver in blocking is illustrated, as well as a maximum-count (MC) receiver, that, when receiving a pulse-position-modulated (PPM) signal, selects the symbol corresponding to the slot with the largest electron count. Whereas the MC receiver saturates at high count rates, the ML receiver may not. The loss in capacity, symbol-error-rate (SER), and count-rate were numerically computed. It was shown that the capacity and symbol-error-rate losses track, whereas the count-rate loss does not generally reflect the SER or capacity loss, as the slot-statistics at the detector output are no longer Poisson. It is also shown that the MC receiver loss may be accurately predicted for dead times on the order of a slot.
NASA Astrophysics Data System (ADS)
Kim, Seonguk; Min, Kyoungdoug
2008-08-01
The CAI (controlled auto ignition) engine ignites fuel and air mixture by trapping high temperature burnt gas using a negative valve overlap. Due to auto ignition in CAI combustion, efficiency improvements and low level NOx emission can be obtained. Meanwhile, the CAI combustion regime is restricted and control parameters are limited. The start of combustion data in the compressed ignition engine are most critical for controlling the overall combustion. In this research, the engine block vibration signal is transformed by the Meyer wavelet to analyze CAI combustion more easily and accurately. Signal acquisition of the engine block vibration is a more suitable method for practical use than measurement of in-cylinder pressure. A new method for detecting combustion start in CAI engines through wavelet transformation of the engine block vibration signal was developed and results indicate that it is accurate enough to analyze the start of combustion. Experimental results show that wavelet transformation of engine block vibration can track the start of combustion in each cycle. From this newly developed method, the start of combustion data in CAI engines can be detected more easily and used as input data for controlling CAI combustion.
Extraocular muscle regeneration in zebrafish requires late signals from Insulin-like growth factors.
Saera-Vila, Alfonso; Louie, Ke'ale W; Sha, Cuilee; Kelly, Ryan M; Kish, Phillip E; Kahana, Alon
2018-01-01
Insulin-like growth factors (Igfs) are key regulators of key biological processes such as embryonic development, growth, and tissue repair and regeneration. The role of Igf in myogenesis is well documented and, in zebrafish, promotes fin and heart regeneration. However, the mechanism of action of Igf in muscle repair and regeneration is not well understood. Using adult zebrafish extraocular muscle (EOM) regeneration as an experimental model, we show that Igf1 receptor blockage using either chemical inhibitors (BMS754807 and NVP-AEW541) or translation-blocking morpholino oligonucleotides (MOs) reduced EOM regeneration. Zebrafish EOMs regeneration depends on myocyte dedifferentiation, which is driven by early epigenetic reprogramming and requires autophagy activation and cell cycle reentry. Inhibition of Igf signaling had no effect on either autophagy activation or cell proliferation, indicating that Igf signaling was not involved in the early reprogramming steps of regeneration. Instead, blocking Igf signaling produced hypercellularity of regenerating EOMs and diminished myosin expression, resulting in lack of mature differentiated muscle fibers even many days after injury, indicating that Igf was involved in late re-differentiation steps. Although it is considered the main mediator of myogenic Igf actions, Akt activation decreased in regenerating EOMs, suggesting that alternative signaling pathways mediate Igf activity in muscle regeneration. In conclusion, Igf signaling is critical for re-differentiation of reprogrammed myoblasts during late steps of zebrafish EOM regeneration, suggesting a regulatory mechanism for determining regenerated muscle size and timing of differentiation, and a potential target for regenerative therapy.
Bölte, S; Hubl, D; Dierks, T; Holtmann, M; Poustka, F
2008-01-01
Autism has been associated with enhanced local processing on visual tasks. Originally, this was based on findings that individuals with autism exhibited peak performance on the block design test (BDT) from the Wechsler Intelligence Scales. In autism, the neurofunctional correlates of local bias on this test have not yet been established, although there is evidence of alterations in the early visual cortex. Functional MRI was used to analyze hemodynamic responses in the striate and extrastriate visual cortex during BDT performance and a color counting control task in subjects with autism compared to healthy controls. In autism, BDT processing was accompanied by low blood oxygenation level-dependent signal changes in the right ventral quadrant of V2. Findings indicate that, in autism, locally oriented processing of the BDT is associated with altered responses of angle and grating-selective neurons, that contribute to shape representation, figure-ground, and gestalt organization. The findings favor a low-level explanation of BDT performance in autism.
Yan, Jianyun; Stringer, Sally E; Hamilton, Andrew; Charlton-Menys, Valentine; Götting, Christian; Müller, Benjamin; Aeschlimann, Daniel; Alexander, M Yvonne
2011-03-01
Decorin and oxidized low-density lipoprotein (Ox-LDL) independently induce osteogenic differentiation of vascular smooth muscle cells (VSMCs). We aimed to determine whether decorin glycosaminoglycan (GAG) chain synthesis contributes to Ox-LDL-induced differentiation and calcification of human VSMCs in vitro. Human VSMCs treated with Ox-LDL to induce oxidative stress showed increased alkaline phosphatase (ALP) activity, accelerated mineralization, and a difference in both decorin GAG chain biosynthesis and CS/DS structure compared with untreated controls. Ox-LDL increased mRNA abundance of both xylosyltransferase (XT)-I, the key enzyme responsible for GAG chain biosynthesis and Msx2, a marker of osteogenic differentiation. Furthermore, downregulation of XT-I expression using small interfering RNA blocked Ox-LDL-induced VSMC mineralization. Adenoviral-mediated overexpression of decorin, but not a mutated unglycanated form, accelerated mineralization of VSMCs, suggesting GAG chain addition on decorin is crucial for the process of differentiation. The decorin-induced VSMC osteogenic differentiation involved activation of the transforming growth factor (TGF)-β pathway, because it was attenuated by blocking of TGF-β receptor signaling and because decorin overexpression potentiated phosphorylation of the downstream signaling molecule smad2. These studies provide direct evidence that oxidative stress-mediated decorin GAG chain synthesis triggers TGF-β signaling and mineralization of VSMCs in vitro.
Valhmu, Wilmot B; Raia, Frank J
2002-01-01
Although the effects of mechanical loading on chondrocyte metabolic activities have been extensively characterized, the sequence of events through which extracellular mechanical signals are transduced into chondrocytes and ultimately modulate cell activities is not well understood. Here, studies were performed to map out the sequential intracellular signalling pathways through which compression-induced signals modulate aggrecan mRNA levels in bovine articular chondrocytes. Bovine articular cartilage explants were subjected to a compressive stress of 0.1 MPa for 1 h in the presence or absence of inhibitors or antagonists of the phosphoinositol and Ca(2+)/calmodulin signalling pathways in order to determine the roles of second messengers and effector molecules of these pathways in transducing the compression-induced signals. In the absence of the inhibitors, aggrecan mRNA levels were stimulated by compression 2-4-fold relative to levels in tare-loaded (see below) explants. Treatment of the explants with graded levels of the protein kinase C inhibitor chelerythrine or bisindolylmaleimide I, followed by 1 h compressive loading, did not significantly alter the load-induced elevation of aggrecan mRNA levels. In contrast, thapsigargin, which depletes the Ins(1,4,5)P3-sensitive intracellular Ca(2+) stores, completely blocked the load response without significantly altering aggrecan mRNA levels in tare-loaded explants. Similarly, antagonists of the Ca(2+)/calmodulin signalling pathway dose-dependently or completely blocked the load-response. The results obtained demonstrate that transduction of the compression-induced aggrecan mRNA-regulating signals requires Ins(1,4,5)P3- and Ca(2+)/calmodulin-dependent signalling processes in bovine articular chondrocytes. PMID:11802800
SDF1 regulates leading process branching and speed of migrating interneurons
Lysko, Daniel E.; Putt, Mary; Golden, Jeffrey A.
2011-01-01
Cell migration is required for normal embryonic development, yet how cells navigate complex paths while integrating multiple guidance cues remains poorly understood. During brain development, interneurons migrate from the ventral ganglionic eminence to the cerebral cortex within several migratory streams. They must exit these streams to invade the cortical plate. While SDF1-signaling is necessary for normal interneuron stream migration, how they switch from tangential stream migration to invade the cortical plate is unknown. Here we demonstrate that SDF1-signaling reduces interneuron branching frequency by reducing cAMP levels via a Gi-signaling pathway using an in vitro mouse explant system, resulting in the maintenance of stream migration. Blocking SDF1-signaling, or increasing branching frequency, results in stream exit and cortical plate invasion in mouse brain slices. These data support a novel model to understand how migrating interneurons switch from tangential migration to invade the cortical plate in which reducing SDF1-signaling increases leading process branching and slows the migration rate, permitting migrating interneurons to sense cortically directed guidance cues. PMID:21289183
cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bhattacharjee, Rajesh; Xiang, Wenpei; Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China
2012-06-22
Highlights: Black-Right-Pointing-Pointer cAMP blocks cell death induced by TNF and actinomycin D in cultured hepatocytes. Black-Right-Pointing-Pointer cAMP blocks NF-{kappa}B activation induced by TNF and actinomycin D. Black-Right-Pointing-Pointer cAMP blocks DISC formation following TNF and actinomycin D exposure. Black-Right-Pointing-Pointer cAMP blocks TNF signaling at a proximal step. -- Abstract: Tumor necrosis factor {alpha} (TNF) is a pleiotropic proinflammatory cytokine that plays a role in immunity and the control of cell proliferation, cell differentiation, and apoptosis. The pleiotropic nature of TNF is due to the formation of different signaling complexes upon the binding of TNF to its receptor, TNF receptor type 1more » (TNFR1). TNF induces apoptosis in various mammalian cells when the cells are co-treated with a transcription inhibitor like actinomycin D (ActD). When TNFR1 is activated, it recruits an adaptor protein, TNF receptor-associated protein with death domain (TRADD), through its cytoplasmic death effector domain (DED). TRADD, in turn, recruits other signaling proteins, including TNF receptor-associated protein 2 (TRAF2) and receptor-associated protein kinase (RIPK) 1, to form a complex. Subsequently, this complex combines with FADD and procaspase-8, converts into a death-inducing signaling complex (DISC) to induce apoptosis. Cyclic AMP (cAMP) is a second messenger that regulates various cellular processes such as cell proliferation, gene expression, and apoptosis. cAMP analogues are reported to act as anti-apoptotic agents in various cell types, including hepatocytes. We found that a cAMP analogue, dibutyryl cAMP (db-cAMP), inhibits TNF + ActD-induced apoptosis in rat hepatocytes. The protein kinase A (PKA) inhibitor KT-5720 reverses this inhibitory effect of cAMP on apoptosis. Cytoprotection by cAMP involves down-regulation of various apoptotic signal regulators like TRADD and FADD and inhibition of caspase-8 and caspase-3 cleavage. We also found that cAMP exerts its affect at the proximal level of TNF signaling by inhibiting the formation of the DISC complex upon the binding of TNF to TNFR1. In conclusion, our study shows that cAMP prevents TNF + ActD-induced apoptosis in rat hepatocytes by inhibiting DISC complex formation.« less
Functional relationship-based alarm processing
Corsberg, D.R.
1987-04-13
A functional relationship-based alarm processing system and method analyzes each alarm as it is activated and determines its relative importance with other currently activated alarms and signals in accordance with the relationships that the newly activated alarm has with other currently activated alarms. Once the initial level of importance of the alarm has been determined, that alarm is again evaluated if another related alarm is activated. Thus, each alarm's importance is continuously updated as the state of the process changes during a scenario. Four hierarchical relationships are defined by this alarm filtering methodology: (1) level precursor (usually occurs when there are two alarm settings on the same parameter); (2) direct precursor (based on causal factors between two alarms); (3) required action (system response or action expected within a specified time following activation of an alarm or combination of alarms and process signals); and (4) blocking condition (alarms that are normally expected and are not considered important). 11 figs.
NASA Technical Reports Server (NTRS)
Duxbury, J. H.
1983-01-01
The JPL's Scientific Data Analysis System (SDAS), which will process IRAS data and produce a catalogue of perhaps a million infrared sources in the sky, as well as other information for astronomical records, is described. The purposes of SDAS are discussed, and the major SDAS processors are shown in block diagram. The catalogue processing is addressed, mentioning the basic processing steps which will be applied to raw detector data. Signal reconstruction and conversion to astrophysical units, source detection, source confirmation, data management, and survey data products are considered in detail.
Computer-Aided Modeling and Analysis of Power Processing Systems (CAMAPPS), phase 1
NASA Technical Reports Server (NTRS)
Kim, S.; Lee, J.; Cho, B. H.; Lee, F. C.
1986-01-01
The large-signal behaviors of a regulator depend largely on the type of power circuit topology and control. Thus, for maximum flexibility, it is best to develop models for each functional block a independent modules. A regulator can then be configured by collecting appropriate pre-defined modules for each functional block. In order to complete the component model generation for a comprehensive spacecraft power system, the following modules were developed: solar array switching unit and control; shunt regulators; and battery discharger. The capability of each module is demonstrated using a simplified Direct Energy Transfer (DET) system. Large-signal behaviors of solar array power systems were analyzed. Stability of the solar array system operating points with a nonlinear load is analyzed. The state-plane analysis illustrates trajectories of the system operating point under various conditions. Stability and transient responses of the system operating near the solar array's maximum power point are also analyzed. The solar array system mode of operation is described using the DET spacecraft power system. The DET system is simulated for various operating conditions. Transfer of the software program CAMAPPS (Computer Aided Modeling and Analysis of Power Processing Systems) to NASA/GSFC (Goddard Space Flight Center) was accomplished.
NASA Astrophysics Data System (ADS)
Sujono, A.; Santoso, B.; Juwana, W. E.
2016-03-01
Problems of detonation (knock) on Otto engine (petrol engine) is completely unresolved problem until now, especially if want to improve the performance. This research did sound vibration signal processing engine with a microphone sensor, for the detection and identification of detonation. A microphone that can be mounted is not attached to the cylinder block, that's high temperature, so that its performance will be more stable, durable and inexpensive. However, the method of analysis is not very easy, because a lot of noise (interference). Therefore the use of new methods of pattern recognition, through filtration, and the regression function normalized envelope. The result is quite good, can achieve a success rate of about 95%.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Hong; Kong, Vic; Ren, Lei
2016-01-15
Purpose: A preobject grid can reduce and correct scatter in cone beam computed tomography (CBCT). However, half of the signal in each projection is blocked by the grid. A synchronized moving grid (SMOG) has been proposed to acquire two complimentary projections at each gantry position and merge them into one complete projection. That approach, however, suffers from increased scanning time and the technical difficulty of accurately merging the two projections per gantry angle. Herein, the authors present a new SMOG approach which acquires a single projection per gantry angle, with complimentary grid patterns for any two adjacent projections, and usemore » an interprojection sensor fusion (IPSF) technique to estimate the blocked signal in each projection. The method may have the additional benefit of reduced imaging dose due to the grid blocking half of the incident radiation. Methods: The IPSF considers multiple paired observations from two adjacent gantry angles as approximations of the blocked signal and uses a weighted least square regression of these observations to finally determine the blocked signal. The method was first tested with a simulated SMOG on a head phantom. The signal to noise ratio (SNR), which represents the difference of the recovered CBCT image to the original image without the SMOG, was used to evaluate the ability of the IPSF in recovering the missing signal. The IPSF approach was then tested using a Catphan phantom on a prototype SMOG assembly installed in a bench top CBCT system. Results: In the simulated SMOG experiment, the SNRs were increased from 15.1 and 12.7 dB to 35.6 and 28.9 dB comparing with a conventional interpolation method (inpainting method) for a projection and the reconstructed 3D image, respectively, suggesting that IPSF successfully recovered most of blocked signal. In the prototype SMOG experiment, the authors have successfully reconstructed a CBCT image using the IPSF-SMOG approach. The detailed geometric features in the Catphan phantom were mostly recovered according to visual evaluation. The scatter related artifacts, such as cupping artifacts, were almost completely removed. Conclusions: The IPSF-SMOG is promising in reducing scatter artifacts and improving image quality while reducing radiation dose.« less
Ji, Bo; Zhao, Guo-Zhen; Sakurai, Reiko; Cao, Yu; Zhang, Zi-Jian; Wang, Dan; Yan, Ming-Na; Rehan, Virender K
2016-08-01
Pregnant women exposed to tobacco smoke predispose the offspring to many adverse consequences including an altered lung development and function. There is no effective therapeutic intervention to block the effects of smoke exposure on the developing lung. Clinical and animal studies demonstrate that acupuncture can modulate a variety of pathophysiological processes, including those involving the respiratory system; however, whether acupuncture affects the lung damage caused by perinatal smoke exposure is not known. To determine the effect of acupuncture on perinatal nicotine exposure on the developing lung, pregnant rat dams were administered (1) saline, (2) nicotine, or (3) nicotine + electroacupuncture (EA). Nicotine was administered (1 mg/kg subcutaneously) once a day and EA was applied to both "Zusanli" (ST 36) points. Both interventions were administered from gestational day 6 to postnatal day 21 (PND21), following which pups were sacrificed. Lungs, blood, and brain were collected to examine markers of lung injury, repair, and hypothalamic pituitary adrenal (HPA) axis. Concomitant EA application blocked nicotine-induced changes in lung morphology, lung peroxisome proliferator-activated receptor γ and wingless-int signaling, two key lung developmental signaling pathways, hypothalamic pituitary adrenal axis (hypothalamic corticotropic releasing hormone and lung glucocorticoid receptor levels), and plasma β-endorphin levels. Electroacupuncture blocks the nicotine-induced changes in lung developmental signaling pathways and the resultant myogenic lung phenotype, known to be present in the affected offspring. We conclude that EA is a promising novel intervention against the smoke exposed lung damage to the developing lung.
DOT National Transportation Integrated Search
2015-04-01
This research examined the safety and operational effects of roadway lane width on mid-block segments between : signalized intersections as well as on signalized intersection approaches in the urban environments of Lincoln and Omaha, : Nebraska. In t...
Wülbeck, Corinna; Grieshaber, Eva; Helfrich-Förster, Charlotte
2009-10-01
The neuropeptide pigment-dispersing factor (PDF) plays an essential role in the circadian clock of the fruit fly Drosophila melanogaster, but many details of PDF signaling in the clock network are still unknown. We tried to interfere with PDF signaling by blocking the GTPase Shibire in PDF neurons. Shibire is an ortholog of the mammalian Dynamins and is essential for endocytosis of clathrin-coated vesicles at the plasma membrane. Such endocytosis is used for neurotransmitter reuptake by presynaptic neurons, which is a prerequisite of synaptic vesicle recycling, and receptor-mediated endocytosis in the postsynaptic neuron, which leads to signal termination. By blocking Shibire function via overexpression of a dominant negative mutant form of Shibire in PDF neurons, we slowed down the behavioral rhythm by 3 h. This effect was absent in PDF receptor null mutants, indicating that we interfered with PDF receptor-mediated endocytosis. Because we obtained similar behavioral phenotypes by increasing the PDF level in regions close to PDF neurons, we conclude that blocking Shibire did prolong PDF signaling in the neurons that respond to PDF. Obviously, terminating the PDF signaling via receptor-mediated endocytosis is a crucial step in determining the period of behavioral rhythms.
Toosi, Tahereh; K Tousi, Ehsan; Esteky, Hossein
2017-08-01
Time is an inseparable component of every physical event that we perceive, yet it is not clear how the brain processes time or how the neuronal representation of time affects our perception of events. Here we asked subjects to perform a visual discrimination task while we changed the temporal context in which the stimuli were presented. We collected electroencephalography (EEG) signals in two temporal contexts. In predictable blocks stimuli were presented after a constant delay relative to a visual cue, and in unpredictable blocks stimuli were presented after variable delays relative to the visual cue. Four subsecond delays of 83, 150, 400, and 800 ms were used in the predictable and unpredictable blocks. We observed that predictability modulated the power of prestimulus alpha oscillations in the parieto-occipital sites: alpha power increased in the 300-ms window before stimulus onset in the predictable blocks compared with the unpredictable blocks. This modulation only occurred in the longest delay period, 800 ms, in which predictability also improved the behavioral performance of the subjects. Moreover, learning the temporal context shaped the prestimulus alpha power: modulation of prestimulus alpha power grew during the predictable block and correlated with performance enhancement. These results suggest that the brain is able to learn the subsecond temporal context of stimuli and use this to enhance sensory processing. Furthermore, the neural correlate of this temporal prediction is reflected in the alpha oscillations. NEW & NOTEWORTHY It is not well understood how the uncertainty in the timing of an external event affects its processing, particularly at subsecond scales. Here we demonstrate how a predictable timing scheme improves visual processing. We found that learning the predictable scheme gradually shaped the prestimulus alpha power. These findings indicate that the human brain is able to extract implicit subsecond patterns in the temporal context of events. Copyright © 2017 the American Physiological Society.
A dynamic multi-channel speech enhancement system for distributed microphones in a car environment
NASA Astrophysics Data System (ADS)
Matheja, Timo; Buck, Markus; Fingscheidt, Tim
2013-12-01
Supporting multiple active speakers in automotive hands-free or speech dialog applications is an interesting issue not least due to comfort reasons. Therefore, a multi-channel system for enhancement of speech signals captured by distributed distant microphones in a car environment is presented. Each of the potential speakers in the car has a dedicated directional microphone close to his position that captures the corresponding speech signal. The aim of the resulting overall system is twofold: On the one hand, a combination of an arbitrary pre-defined subset of speakers' signals can be performed, e.g., to create an output signal in a hands-free telephone conference call for a far-end communication partner. On the other hand, annoying cross-talk components from interfering sound sources occurring in multiple different mixed output signals are to be eliminated, motivated by the possibility of other hands-free applications being active in parallel. The system includes several signal processing stages. A dedicated signal processing block for interfering speaker cancellation attenuates the cross-talk components of undesired speech. Further signal enhancement comprises the reduction of residual cross-talk and background noise. Subsequently, a dynamic signal combination stage merges the processed single-microphone signals to obtain appropriate mixed signals at the system output that may be passed to applications such as telephony or a speech dialog system. Based on signal power ratios between the particular microphone signals, an appropriate speaker activity detection and therewith a robust control mechanism of the whole system is presented. The proposed system may be dynamically configured and has been evaluated for a car setup with four speakers sitting in the car cabin disturbed in various noise conditions.
Wright, David L; Magnuson, Curt E; Black, Charles B
2005-09-01
Individuals practiced two unique discrete sequence production tasks that differed in their relative time profile in either a blocked or random practice schedule. Each participant was subsequently administered a "precuing" protocol to examine the cost of initially compiling or modifying the plan for an upcoming movement's relative timing. The findings indicated that, in general, random practice facilitated the programming of the required movement timing, and this was accomplished while exhibiting greater accuracy in movement production. Participants exposed to random practice exhibited the greatest motor programming benefit, when a modification to an already prepared movement timing profile was required. When movement timing was only partially constructed prior to the imperative signal, the individuals who were trained in blocked and random practice formats accrued a similar cost to complete the programming process. These data provide additional support for the recent claim of Immink & Wright (2001) that at least some of the benefit from experience in a random as opposed to blocked training context can be localized to superior development and implementation of the motor programming process before executing the movement.
FPGA-based firmware model for extended measurement systems with data quality monitoring
NASA Astrophysics Data System (ADS)
Wojenski, A.; Pozniak, K. T.; Mazon, D.; Chernyshova, M.
2017-08-01
Modern physics experiments requires construction of advanced, modular measurement systems for data processing and registration purposes. Components are often designed in one of the common mechanical and electrical standards, e.g. VME or uTCA. The paper is focused on measurement systems using FPGAs as data processing blocks, especially for plasma diagnostics using GEM detectors with data quality monitoring aspects. In the article is proposed standardized model of HDL FPGA firmware implementation, for use in a wide range of different measurement system. The effort was made in term of flexible implementation of data quality monitoring along with source data dynamic selection. In the paper is discussed standard measurement system model followed by detailed model of FPGA firmware for modular measurement systems. Considered are both: functional blocks and data buses. In the summary, necessary blocks and signal lines are described. Implementation of firmware following the presented rules should provide modular design, with ease of change different parts of it. The key benefit is construction of universal, modular HDL design, that can be applied in different measurement system with simple adjustments.
Experimental Demonstration of Photon Efficient Coherent Temporal Combining for Data Rate Scaling
2016-02-15
combining with pre-amplified Distribution A: Public Release. This work was sponsored by the Assistant Secretary of Defense for Research and Engineering...for -96 dBm signal with 211-1 points after block repeating and combining the waveform various number of block repeats (N). The blue dots and red...particular, Figure 5 shows constellation diagrams for the -96 dBm signal after temporal coherent combining of 4,000, 8,000, 16,000, 32,000, and 36,000 block
Implementation and optimization of ultrasound signal processing algorithms on mobile GPU
NASA Astrophysics Data System (ADS)
Kong, Woo Kyu; Lee, Wooyoul; Kim, Kyu Cheol; Yoo, Yangmo; Song, Tai-Kyong
2014-03-01
A general-purpose graphics processing unit (GPGPU) has been used for improving computing power in medical ultrasound imaging systems. Recently, a mobile GPU becomes powerful to deal with 3D games and videos at high frame rates on Full HD or HD resolution displays. This paper proposes the method to implement ultrasound signal processing on a mobile GPU available in the high-end smartphone (Galaxy S4, Samsung Electronics, Seoul, Korea) with programmable shaders on the OpenGL ES 2.0 platform. To maximize the performance of the mobile GPU, the optimization of shader design and load sharing between vertex and fragment shader was performed. The beamformed data were captured from a tissue mimicking phantom (Model 539 Multipurpose Phantom, ATS Laboratories, Inc., Bridgeport, CT, USA) by using a commercial ultrasound imaging system equipped with a research package (Ultrasonix Touch, Ultrasonix, Richmond, BC, Canada). The real-time performance is evaluated by frame rates while varying the range of signal processing blocks. The implementation method of ultrasound signal processing on OpenGL ES 2.0 was verified by analyzing PSNR with MATLAB gold standard that has the same signal path. CNR was also analyzed to verify the method. From the evaluations, the proposed mobile GPU-based processing method has no significant difference with the processing using MATLAB (i.e., PSNR<52.51 dB). The comparable results of CNR were obtained from both processing methods (i.e., 11.31). From the mobile GPU implementation, the frame rates of 57.6 Hz were achieved. The total execution time was 17.4 ms that was faster than the acquisition time (i.e., 34.4 ms). These results indicate that the mobile GPU-based processing method can support real-time ultrasound B-mode processing on the smartphone.
NASA Astrophysics Data System (ADS)
Huang, Yan; Wang, Zhihui
2015-12-01
With the development of FPGA, DSP Builder is widely applied to design system-level algorithms. The algorithm of CL multi-wavelet is more advanced and effective than scalar wavelets in processing signal decomposition. Thus, a system of CL multi-wavelet based on DSP Builder is designed for the first time in this paper. The system mainly contains three parts: a pre-filtering subsystem, a one-level decomposition subsystem and a two-level decomposition subsystem. It can be converted into hardware language VHDL by the Signal Complier block that can be used in Quartus II. After analyzing the energy indicator, it shows that this system outperforms Daubenchies wavelet in signal decomposition. Furthermore, it has proved to be suitable for the implementation of signal fusion based on SoPC hardware, and it will become a solid foundation in this new field.
Code of Federal Regulations, 2011 CFR
2011-10-01
... OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Train Stop, Train Control and Cab Signal Systems Standards § 236.502 Automatic brake application, initiation by restrictive block conditions stopping distance in advance. An automatic train-stop or train-control system shall operate to...
Code of Federal Regulations, 2011 CFR
2011-10-01
... TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Traffic Control Systems Standards § 236.401 Automatic... 49 Transportation 4 2011-10-01 2011-10-01 false Automatic block signal system and interlocking standards applicable to traffic control systems. 236.401 Section 236.401 Transportation Other Regulations...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Hanfeng; Britton, Charles; Quaiyum, Farhan
With increasing emphasis on implantable and portable medical devices, low-power, small-chip-area sensor readout system realized in lab-on-a-chip (LOC) platform is gaining more and more importance these days. The main building blocks of the LOC system include a front-end transducer that generates an electrical signal in response to the presence of an analyte of interest, signal processing electronics to process the signal to comply with a specific transmission protocol and a low-power transmitter, all realized in a single integrated circuit platform. Low power consumption and compactness of the components are essential requirements of the LOC system. This paper presents a novelmore » charge sensitive pre-amplifier developed in a standard 180-nm CMOS process suitable for implementing in an LOC platform. The pre-amplifier converts the charge generated by a pyroelectric transducer into a voltage signal, which provides a measurement of the temperature variation in biological fluids. The proposed design is capable of providing 0.8-mV/pC gain while consuming only 2.1 μW of power. Finally, the pre-amplifier composed of integrated components occupies an area of 0.038 mm 2.« less
Wang, Hanfeng; Britton, Charles; Quaiyum, Farhan; ...
2018-01-01
With increasing emphasis on implantable and portable medical devices, low-power, small-chip-area sensor readout system realized in lab-on-a-chip (LOC) platform is gaining more and more importance these days. The main building blocks of the LOC system include a front-end transducer that generates an electrical signal in response to the presence of an analyte of interest, signal processing electronics to process the signal to comply with a specific transmission protocol and a low-power transmitter, all realized in a single integrated circuit platform. Low power consumption and compactness of the components are essential requirements of the LOC system. This paper presents a novelmore » charge sensitive pre-amplifier developed in a standard 180-nm CMOS process suitable for implementing in an LOC platform. The pre-amplifier converts the charge generated by a pyroelectric transducer into a voltage signal, which provides a measurement of the temperature variation in biological fluids. The proposed design is capable of providing 0.8-mV/pC gain while consuming only 2.1 μW of power. Finally, the pre-amplifier composed of integrated components occupies an area of 0.038 mm 2.« less
New Directions in the Digital Signal Processing of Image Data.
1987-05-01
and identify by block number) FIELD GROUP SUB-GROUP Object detection and idLntification 12 01 restoration of photon noise limited imagery 15 04 image...from incomplete information, restoration of blurred images in additive and multiplicative noise , motion analysis with fast hierarchical algorithms...different resolutions. As is well known, the solution to the matched filter problem under additive white noise conditions is the correlation receiver
Cui, Jingqiu; Chen, Wei; Sun, Jinhong; Guo, Huan; Madley, Rachel; Xiong, Yi; Pan, Xingyi; Wang, Hongliang; Tai, Andrew W.; Weiss, Michael A.; Arvan, Peter; Liu, Ming
2015-01-01
Upon translocation across the endoplasmic reticulum (ER) membrane, secretory proteins are proteolytically processed to remove their signal peptide by signal peptidase (SPase). This process is critical for subsequent folding, intracellular trafficking, and maturation of secretory proteins. Prokaryotic SPase has been shown to be a promising antibiotic target. In contrast, to date, no eukaryotic SPase inhibitors have been reported. Here we report that introducing a proline immediately following the natural signal peptide cleavage site not only blocks preprotein cleavage but also, in trans, impairs the processing and maturation of co-expressed preproteins in the ER. Specifically, we find that a variant preproinsulin, pPI-F25P, is translocated across the ER membrane, where it binds to the catalytic SPase subunit SEC11A, inhibiting SPase activity in a dose-dependent manner. Similar findings were obtained with an analogous variant of preproparathyroid hormone, demonstrating that inhibition of the SPase does not depend strictly on the sequence or structure of the downstream mature protein. We further show that inhibiting SPase in the ER impairs intracellular processing of viral polypeptides and their subsequent maturation. These observations suggest that eukaryotic SPases (including the human ortholog) are, in principle, suitable therapeutic targets for antiviral drug design. PMID:26446786
Process simulation in digital camera system
NASA Astrophysics Data System (ADS)
Toadere, Florin
2012-06-01
The goal of this paper is to simulate the functionality of a digital camera system. The simulations cover the conversion from light to numerical signal and the color processing and rendering. We consider the image acquisition system to be linear shift invariant and axial. The light propagation is orthogonal to the system. We use a spectral image processing algorithm in order to simulate the radiometric properties of a digital camera. In the algorithm we take into consideration the transmittances of the: light source, lenses, filters and the quantum efficiency of a CMOS (complementary metal oxide semiconductor) sensor. The optical part is characterized by a multiple convolution between the different points spread functions of the optical components. We use a Cooke triplet, the aperture, the light fall off and the optical part of the CMOS sensor. The electrical part consists of the: Bayer sampling, interpolation, signal to noise ratio, dynamic range, analog to digital conversion and JPG compression. We reconstruct the noisy blurred image by blending different light exposed images in order to reduce the photon shot noise, also we filter the fixed pattern noise and we sharpen the image. Then we have the color processing blocks: white balancing, color correction, gamma correction, and conversion from XYZ color space to RGB color space. For the reproduction of color we use an OLED (organic light emitting diode) monitor. The analysis can be useful to assist students and engineers in image quality evaluation and imaging system design. Many other configurations of blocks can be used in our analysis.
Code of Federal Regulations, 2010 CFR
2010-10-01
... restrictive block conditions stopping distance in advance. 236.502 Section 236.502 Transportation Other... Cab Signal Systems Standards § 236.502 Automatic brake application, initiation by restrictive block... initiate an automatic brake application at least stopping distance from the entrance to a block, wherein...
Analysis of thin fractures with GPR: from theory to practice
NASA Astrophysics Data System (ADS)
Arosio, Diego; Zanzi, Luigi; Longoni, Laura; Papini, Monica
2017-04-01
Whenever we perform a GPR survey to investigate a rocky medium, being the ultimate purpose of the survey either to study the stability of a rock slope or to determine the soundness of a quarried rock block, we would like mainly to detect any fracture within the investigated medium and, possibly, to estimate the parameters of the fractures, namely thickness and filling material. In most of the practical cases, rock fracture thicknesses are very small when compared to the wavelength of the electromagnetic radiation generated by the GPR systems. In such cases, fractures are to be considered as thin beds, i.e. two interfaces whose distance is smaller than GPR resolving capability, and the reflected signal is the sum of the electromagnetic reverberation within the bed. According to this, fracture parameters are encoded in the thin bed complex response and in this work we propose a methodology based on deterministic deconvolution to process amplitude and phase information in the frequency domain to estimate fracture parameters. We first present some theoretical aspects related to thin bed response and a sensitivity analysis concerning fracture thickness and filling. Secondly, we deal with GPR datasets collected both during laboratory experiments and in the facilities of quarrying activities. In the lab tests fractures were simulated by placing materials with known electromagnetic parameters and controlled thickness in between two small marble blocks, whereas field GPR surveys were performed on bigger quarried ornamental stone blocks before they were submitted to the cutting process. We show that, with basic pre-processing and the choice of a proper deconvolving signal, results are encouraging although an ambiguity between thickness and filling estimates exists when no a-priori information is available. Results can be improved by performing CMP radar surveys that are able to provide additional information (i.e., variation of thin bed response versus offset) at the expense of acquisition effort and of more complex and tricky pre-processing sequences.
Barbaro, V; Bartolini, P; Calcagnini, G; Censi, F; Beard, B; Ruggera, P; Witters, D
2003-06-07
The aim of this study was to investigate the mechanisms by which the radiated radiofrequency (RF) GSM (global system for mobile communication) signal may affect pacemaker (PM) function. We measured the signal at the output of the sensing amplifier of PMs with various configurations of low-pass filters. We used three versions of the same PM model: one with a block capacitor which short circuits high-frequency signals; one with a ceramic feedthrough capacitor, a hermetically sealed mechanism connecting the internal electronics to the external connection block, and one with both. The PMs had been modified to have an electrical shielded connection to the output of the sensing amplifier. For each PM, the output of the sensing amplifier was monitored under exposure to modulated and non-modulated RF signals, and to GSM signals (900 and 1800 MHz). Non-modulated RF signals did not alter the response of the PM sensing amplifier. Modulated RF signals showed that the block capacitor did not succeed in short circuiting the RF signal, which is somehow demodulated by the PM internal non-linear circuit elements. Such a demodulation phenomenon poses a critical problem because digital cellular phones use extremely low-frequency modulation (as low as 2 Hz). which can be mistaken for normal heartbeat.
Biosignals learning and synthesis using deep neural networks.
Belo, David; Rodrigues, João; Vaz, João R; Pezarat-Correia, Pedro; Gamboa, Hugo
2017-09-25
Modeling physiological signals is a complex task both for understanding and synthesize biomedical signals. We propose a deep neural network model that learns and synthesizes biosignals, validated by the morphological equivalence of the original ones. This research could lead the creation of novel algorithms for signal reconstruction in heavily noisy data and source detection in biomedical engineering field. The present work explores the gated recurrent units (GRU) employed in the training of respiration (RESP), electromyograms (EMG) and electrocardiograms (ECG). Each signal is pre-processed, segmented and quantized in a specific number of classes, corresponding to the amplitude of each sample and fed to the model, which is composed by an embedded matrix, three GRU blocks and a softmax function. This network is trained by adjusting its internal parameters, acquiring the representation of the abstract notion of the next value based on the previous ones. The simulated signal was generated by forecasting a random value and re-feeding itself. The resulting generated signals are similar with the morphological expression of the originals. During the learning process, after a set of iterations, the model starts to grasp the basic morphological characteristics of the signal and later their cyclic characteristics. After training, these models' prediction are closer to the signals that trained them, specially the RESP and ECG. This synthesis mechanism has shown relevant results that inspire the use to characterize signals from other physiological sources.
Study on a novel laser target detection system based on software radio technique
NASA Astrophysics Data System (ADS)
Song, Song; Deng, Jia-hao; Wang, Xue-tian; Gao, Zhen; Sun, Ji; Sun, Zhi-hui
2008-12-01
This paper presents that software radio technique is applied to laser target detection system with the pseudo-random code modulation. Based on the theory of software radio, the basic framework of the system, hardware platform, and the implementation of the software system are detailed. Also, the block diagram of the system, DSP circuit, block diagram of the pseudo-random code generator, and soft flow diagram of signal processing are designed. Experimental results have shown that the application of software radio technique provides a novel method to realize the modularization, miniaturization and intelligence of the laser target detection system, and the upgrade and improvement of the system will become simpler, more convenient, and cheaper.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Caignard, Gregory; Guerbois, Mathilde; Labernardiere, Jean-Louis
2007-11-25
Viruses have evolved various strategies to escape the antiviral activity of type I interferons (IFN-{alpha}/{beta}). For measles virus, this function is carried by the polycistronic gene P that encodes, by an unusual editing strategy, for the phosphoprotein P and the virulence factor V (MV-V). MV-V prevents STAT1 nuclear translocation by either sequestration or phosphorylation inhibition, thereby blocking IFN-{alpha}/{beta} pathway. We show that both the N- and C-terminal domains of MV-V (PNT and VCT) contribute to the inhibition of IFN-{alpha}/{beta} signaling. Using the two-hybrid system and co-affinity purification experiments, we identified STAT1 and Jak1 as interactors of MV-V and demonstrate thatmore » MV-V can block the direct phosphorylation of STAT1 by Jak1. A deleterious mutation within the PNT domain of MV-V (Y110H) impaired its ability to interact and block STAT1 phosphorylation. Thus, MV-V interacts with at least two components of IFN-{alpha}/{beta} receptor complex to block downstream signaling.« less
Subliminal stimulation and somatosensory signal detection.
Ferrè, Elisa Raffaella; Sahani, Maneesh; Haggard, Patrick
2016-10-01
Only a small fraction of sensory signals is consciously perceived. The brain's perceptual systems may include mechanisms of feedforward inhibition that protect the cortex from subliminal noise, thus reserving cortical capacity and conscious awareness for significant stimuli. Here we provide a new view of these mechanisms based on signal detection theory, and gain control. We demonstrated that subliminal somatosensory stimulation decreased sensitivity for the detection of a subsequent somatosensory input, largely due to increased false alarm rates. By delivering the subliminal somatosensory stimulus and the to-be-detected somatosensory stimulus to different digits of the same hand, we show that this effect spreads across the sensory surface. In addition, subliminal somatosensory stimulation tended to produce an increased probability of responding "yes", whether the somatosensory stimulus was present or not. Our results suggest that subliminal stimuli temporarily reduce input gain, avoiding excessive responses to further small inputs. This gain control may be automatic, and may precede discriminative classification of inputs into signals or noise. Crucially, we found that subliminal inputs influenced false alarm rates only on blocks where the to-be-detected stimuli were present, and not on pre-test control blocks where they were absent. Participants appeared to adjust their perceptual criterion according to a statistical distribution of stimuli in the current context, with the presence of supraliminal stimuli having an important role in the criterion-setting process. These findings clarify the cognitive mechanisms that reserve conscious perception for salient and important signals. Copyright © 2016 Elsevier B.V. All rights reserved.
Xing, Yu; Chen, Wei-hua; Jia, Wensuo; Zhang, Jianhua
2015-01-01
Superoxide dismutases (SODs) are involved in plant adaptive responses to biotic and abiotic stresses but the upstream signalling process that modulates their expression is not clear. Expression of two iron SODs, FSD2 and FSD3, was significantly increased in Arabidopsis in response to NaCl treatment but blocked in transgenic MKK5-RNAi plant, mkk5. Using an assay system for transient expression in protoplasts, it was found that mitogen-activated protein kinase kinase 5 (MKK5) was also activated in response to salt stress. Overexpression of MKK5 in wild-type plants enhanced their tolerance to salt treatments, while mkk5 mutant exhibited hypersensitivity to salt stress in germination on salt-containing media. Moreover, another kinase, MPK6, was also involved in the MKK5-mediated iron superoxide dismutase (FSD) signalling pathway in salt stress. The kinase activity of MPK6 was totally turned off in mkk5, whereas the activity of MPK3 was only partially blocked. MKK5 interacted with the MEKK1 protein that was also involved in the salt-induced FSD signalling pathway. These data suggest that salt-induced FSD2 and FSD3 expressions are influenced by MEKK1 via MKK5–MPK6-coupled signalling. This MAP kinase cascade (MEKK1, MKK5, and MPK6) mediates the salt-induced expression of iron superoxide dismutases. PMID:26136265
Semi-Automatic Determination of Rockfall Trajectories
Volkwein, Axel; Klette, Johannes
2014-01-01
In determining rockfall trajectories in the field, it is essential to calibrate and validate rockfall simulation software. This contribution presents an in situ device and a complementary Local Positioning System (LPS) that allow the determination of parts of the trajectory. An assembly of sensors (herein called rockfall sensor) is installed in the falling block recording the 3D accelerations and rotational velocities. The LPS automatically calculates the position of the block along the slope over time based on Wi-Fi signals emitted from the rockfall sensor. The velocity of the block over time is determined through post-processing. The setup of the rockfall sensor is presented followed by proposed calibration and validation procedures. The performance of the LPS is evaluated by means of different experiments. The results allow for a quality analysis of both the obtained field data and the usability of the rockfall sensor for future/further applications in the field. PMID:25268916
A scalable SIMD digital signal processor for high-quality multifunctional printer systems
NASA Astrophysics Data System (ADS)
Kang, Hyeong-Ju; Choi, Yongwoo; Kim, Kimo; Park, In-Cheol; Kim, Jung-Wook; Lee, Eul-Hwan; Gahang, Goo-Soo
2005-01-01
This paper describes a high-performance scalable SIMD digital signal processor (DSP) developed for multifunctional printer systems. The DSP supports a variable number of datapaths to cover a wide range of performance and maintain a RISC-like pipeline structure. Many special instructions suitable for image processing algorithms are included in the DSP. Quad/dual instructions are introduced for 8-bit or 16-bit data, and bit-field extraction/insertion instructions are supported to process various data types. Conditional instructions are supported to deal with complex relative conditions efficiently. In addition, an intelligent DMA block is integrated to align data in the course of data reading. Experimental results show that the proposed DSP outperforms a high-end printer-system DSP by at least two times.
Kangsamaksin, Thaned; Murtomaki, Aino; Kofler, Natalie M.; Cuervo, Henar; Chaudhri, Reyhaan A.; Tattersall, Ian W.; Rosenstiel, Paul E.; Shawber, Carrie J.; Kitajewski, Jan
2015-01-01
A pro-angiogenic role for Jagged-dependent activation of Notch signaling in the endothelium has yet to be described. Using proteins that encoded different NOTCH1 EGF-like repeats, we identified unique regions of DLL-class and JAG-class ligand/receptor interactions, and developed Notch decoys that function as ligand-specific Notch inhibitors. N110-24 decoy blocked JAG1/JAG2-mediated NOTCH1 signaling, angiogenic sprouting in vitro and retinal angiogenesis, demonstrating JAG-dependent Notch signal activation promotes angiogenesis. In tumors, N110-24 decoy reduced angiogenic sprouting, vessel perfusion, pericyte coverage, and tumor growth. JAG/NOTCH signaling uniquely inhibited expression of anti-angiogenic sVEFGFR-1/sFlt-1. N11-13 decoy interfered with DLL1/DLL4-mediated NOTCH1 signaling and caused endothelial hypersprouting in vitro, in retinal angiogenesis and in tumors. Thus, blockade of JAG- or DLL-mediated Notch signaling inhibits angiogenesis by distinct mechanisms. JAG/Notch signaling positively regulates angiogenesis by suppressing sVEGFR-1/sFlt-1 and promoting mural/endothelial cell interactions. Blockade of JAG-class ligands represents a novel, viable therapeutic approach to block tumor angiogenesis and growth. PMID:25387766
49 CFR 236.202 - Signal governing movements over hand-operated switch.
Code of Federal Regulations, 2011 CFR
2011-10-01
... THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.202 Signal governing movements over hand...
Barquilla, Antonio; Lamberto, Ilaria; Noberini, Roberta; Heynen-Genel, Susanne; Brill, Laurence M; Pasquale, Elena B
2016-09-01
The EphA2 receptor tyrosine kinase plays key roles in tissue homeostasis and disease processes such as cancer, pathological angiogenesis, and inflammation through two distinct signaling mechanisms. EphA2 "canonical" signaling involves ephrin-A ligand binding, tyrosine autophosphorylation, and kinase activity; EphA2 "noncanonical" signaling involves phosphorylation of serine 897 (S897) by AKT and RSK kinases. To identify small molecules counteracting EphA2 canonical signaling, we developed a high-content screening platform measuring inhibition of ephrin-A1-induced PC3 prostate cancer cell retraction. Surprisingly, most hits from a screened collection of pharmacologically active compounds are agents that elevate intracellular cAMP by activating G protein-coupled receptors such as the β2-adrenoceptor. We found that cAMP promotes phosphorylation of S897 by protein kinase A (PKA) as well as increases the phosphorylation of several nearby serine/threonine residues, which constitute a phosphorylation hotspot. Whereas EphA2 canonical and noncanonical signaling have been viewed as mutually exclusive, we show that S897 phosphorylation by PKA can coexist with EphA2 tyrosine phosphorylation and block cell retraction induced by EphA2 kinase activity. Our findings reveal a novel paradigm in EphA2 function involving the interplay of canonical and noncanonical signaling and highlight the ability of the β2-adrenoceptor/cAMP/PKA axis to rewire EphA2 signaling in a subset of cancer cells. © 2016 Barquilla et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
DOE Office of Scientific and Technical Information (OSTI.GOV)
Retamales, A.; Zuloaga, R.; Valenzuela, C.A.
Myogenic differentiation is a complex and well-coordinated process for generating mature skeletal muscle fibers. This event is autocrine/paracrine regulated by growth factors, principally Myostatin (MSTN) and Insulin-like Growth Factor-1 (IGF-1). Myostatin, a member of the transforming growth factor-β superfamily, is a negative regulator of skeletal muscle growth in vertebrates that exerts its inhibitory function by activating Smad transcription factors. In contrast, IGF-1 promotes the differentiation of skeletal myoblasts by activating the PI3K/Akt signaling pathway. This study reports on a novel functional crosstalk between the IGF-1 and MSTN signaling pathways, as mediated through interaction between PI3K/Akt and Smad3. Stimulation of skeletalmore » myoblasts with MSTN resulted in a transient increase in the pSmad3:Smad3 ratio and Smad-dependent transcription. Moreover, MSTN inhibited myod gene expression and myoblast fusion in an Activin receptor-like kinase/Smad3-dependent manner. Preincubation of skeletal myoblasts with IGF-1 blocked MSTN-induced Smad3 activation, promoting myod expression and myoblast differentiation. This inhibitory effect of IGF-1 on the MSTN signaling pathway was dependent on IGF-1 receptor, PI3K, and Akt activities. Finally, immunoprecipitation assay analysis determined that IGF-1 pretreatment increased Akt and Smad3 interaction. These results demonstrate that the IGF-1/PI3K/Akt pathway may inhibit MSTN signaling during myoblast differentiation, providing new insight to existing knowledge on the complex crosstalk between both growth factors. - Highlights: • IGF-1 inhibits Myostatin canonical signaling pathway through IGF-1R/PI3K/Akt pathway. • IGF-1 promotes myoblast differentiation through a direct blocking of Myostatin signaling pathway. • IGF-1 induces the interaction of Akt with Smad3 in skeletal myoblast.« less
Qiao, W; Li, A G; Owens, P; Xu, X; Wang, X-J; Deng, C-X
2006-01-12
Smad4 is the common mediator for TGFbeta signals, which play important functions in many biological processes. To study the role of Smad4 in skin development and epidermal tumorigenesis, we disrupted this gene in skin using the Cre-loxP approach. We showed that absence of Smad4 blocked hair follicle differentiation and cycling, leading to a progressive hair loss of mutant (MT) mice. MT hair follicles exhibited diminished expression of Lef1, and increased proliferative cells in the outer root sheath. Additionally, the skin of MT mice exhibited increased proliferation of basal keratinocytes and epidermal hyperplasia. Furthermore, we provide evidence that the absence of Smad4 resulted in a block of both TGFbeta and bone morphogenetic protein (BMP) signaling pathways, including p21, a well-known cyclin-dependent kinase inhibitor. Consequently, all MT mice developed spontaneous malignant skin tumors from 3 months to 13 months of age. The majority of tumors are malignant squamous cell carcinomas. A most notable finding is that tumorigenesis is accompanied by inactivation of phosphatase and tensin homolog deleted on chromosome 10 (Pten), activation of AKT, fast proliferation and nuclear accumulation of cyclin D1. These observations revealed the essential functions of Smad4-mediated signals in repressing skin tumor formation through the TGFbeta/BMP pathway, which interacts with the Pten signaling pathway.
Jing Li, Jing; Szkudlarek, Hanna; Renard, Justine; Hudson, Roger; Rushlow, Walter; Laviolette, Steven R
2018-05-09
Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder and opioid addiction. Transmission through PFC DA D4 receptors (D4Rs) has been shown to potentiate the emotional salience of normally nonsalient emotional memories, whereas transmission through PFC DA D1 receptors (D1Rs) has been demonstrated to selectively block recall of reward- or aversion-related associative memories. In the present study, using a combination of fear conditioning and opiate reward conditioning in male rats, we examined the role of PFC D4/D1R signaling during the processing of fear-related memory acquisition and recall and subsequent sensitivity to opiate reward memory formation. We report that PFC D4R activation potentiates the salience of normally subthreshold fear conditioning memory cues and simultaneously potentiates the rewarding effects of systemic or intra-ventral tegmental area (VTA) morphine conditioning cues. In contrast, blocking the recall of salient fear memories with intra-PFC D1R activation, blocks the ability of fear memory recall to potentiate systemic or intra-VTA morphine place preference. These effects were dependent upon dissociable PFC phosphorylation states involving calcium-calmodulin-kinase II or extracellular signal-related kinase 1-2, following intra-PFC D4 or D1R activation, respectively. Together, these findings reveal new insights into how aberrant PFC DAergic transmission and associated downstream molecular signaling pathways may modulate fear-related emotional memory processing and concomitantly increase opioid addiction vulnerability. SIGNIFICANCE STATEMENT Post-traumatic stress disorder is highly comorbid with addiction. In this study, we use a translational model of fear memory conditioning to examine how transmission through dopamine D1 or D4 receptors, in the prefrontal cortex (PFC), may differentially control acquisition or recall of fear memories and how these mechanisms might regulate sensitivity to the rewarding effects of opioids. We demonstrate that PFC D4 activation not only controls the salience of fear memory acquisition, but potentiates the rewarding effects of opioids. In contrast, PFC D1 receptor activation blocks recall of fear memories and prevents potentiation of opioid reward effects. Together, these findings demonstrate novel PFC mechanisms that may account for how emotional memory disturbances might increase the addictive liability of opioid-class drugs. Copyright © 2018 the authors 0270-6474/18/384543-13$15.00/0.
Protein Tyrosine Phosphatase 1B (PTP1B): A Potential Target for Alzheimer's Therapy?
Vieira, Marcelo N N; Lyra E Silva, Natalia M; Ferreira, Sergio T; De Felice, Fernanda G
2017-01-01
Despite significant advances in current understanding of mechanisms of pathogenesis in Alzheimer's disease (AD), attempts at drug development based on those discoveries have failed to translate into effective, disease-modifying therapies. AD is a complex and multifactorial disease comprising a range of aberrant cellular/molecular processes taking part in different cell types and brain regions. As a consequence, therapeutics for AD should be able to block or compensate multiple abnormal pathological events. Here, we examine recent evidence that inhibition of protein tyrosine phosphatase 1B (PTP1B) may represent a promising strategy to combat a variety of AD-related detrimental processes. Besides its well described role as a negative regulator of insulin and leptin signaling, PTB1B recently emerged as a modulator of various other processes in the central nervous system (CNS) that are also implicated in AD. These include signaling pathways germane to learning and memory, regulation of synapse dynamics, endoplasmic reticulum (ER) stress and microglia-mediated neuroinflammation. We propose that PTP1B inhibition may represent an attractive and yet unexplored therapeutic approach to correct aberrant signaling pathways linked to AD.
NASA Astrophysics Data System (ADS)
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.
49 CFR 236.204 - Track signaled for movements in both directions, requirements.
Code of Federal Regulations, 2010 CFR
2010-10-01
... THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.204 Track signaled for movements in both...
49 CFR 236.204 - Track signaled for movements in both directions, requirements.
Code of Federal Regulations, 2011 CFR
2011-10-01
... THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.204 Track signaled for movements in both...
NASA Astrophysics Data System (ADS)
Yu, Fei; Hui, Mei; Zhao, Yue-jin
2009-08-01
The image block matching algorithm based on motion vectors of correlative pixels in oblique direction is presented for digital image stabilization. The digital image stabilization is a new generation of image stabilization technique which can obtains the information of relative motion among frames of dynamic image sequences by the method of digital image processing. In this method the matching parameters are calculated from the vectors projected in the oblique direction. The matching parameters based on the vectors contain the information of vectors in transverse and vertical direction in the image blocks at the same time. So the better matching information can be obtained after making correlative operation in the oblique direction. And an iterative weighted least square method is used to eliminate the error of block matching. The weights are related with the pixels' rotational angle. The center of rotation and the global emotion estimation of the shaking image can be obtained by the weighted least square from the estimation of each block chosen evenly from the image. Then, the shaking image can be stabilized with the center of rotation and the global emotion estimation. Also, the algorithm can run at real time by the method of simulated annealing in searching method of block matching. An image processing system based on DSP was used to exam this algorithm. The core processor in the DSP system is TMS320C6416 of TI, and the CCD camera with definition of 720×576 pixels was chosen as the input video signal. Experimental results show that the algorithm can be performed at the real time processing system and have an accurate matching precision.
Triggers of key calcium signals during erythrocyte invasion by Plasmodium falciparum
Gao, Xiaohong; Gunalan, Karthigayan; Yap, Sally Shu Lin; Preiser, Peter R.
2013-01-01
Invasion of erythrocytes by Plasmodium falciparum merozoites is a complex multi-step process mediated by specific interactions between host receptors and parasite ligands. Reticulocyte-binding protein homologues (RHs) and erythrocyte-binding-like (EBL) proteins are discharged from specialized organelles and used in early steps of invasion. Here we show that monoclonal antibodies against PfRH1 (an RH) block merozoite invasion by specifically inhibiting calcium signalling in the parasite, whereas invasion-inhibiting monoclonal antibodies targeting EBA175 (an EBL protein) have no effect on signalling. We further show that inhibition of this calcium signalling prevents EBA175 discharge and thereby formation of the junction between parasite and host cell. Our results indicate that PfRH1 has an initial sensing as well as signal transduction role that leads to the subsequent release of EBA175. They also provide new insights on how RH–host cell interactions lead to essential downstream signalling events in the parasite, suggesting new targets for malaria intervention. PMID:24280897
Developing Signal-Pattern-Recognition Programs
NASA Technical Reports Server (NTRS)
Shelton, Robert O.; Hammen, David
2006-01-01
Pattern Interpretation and Recognition Application Toolkit Environment (PIRATE) is a block-oriented software system that aids the development of application programs that analyze signals in real time in order to recognize signal patterns that are indicative of conditions or events of interest. PIRATE was originally intended for use in writing application programs to recognize patterns in space-shuttle telemetry signals received at Johnson Space Center's Mission Control Center: application programs were sought to (1) monitor electric currents on shuttle ac power busses to recognize activations of specific power-consuming devices, (2) monitor various pressures and infer the states of affected systems by applying a Kalman filter to the pressure signals, (3) determine fuel-leak rates from sensor data, (4) detect faults in gyroscopes through analysis of system measurements in the frequency domain, and (5) determine drift rates in inertial measurement units by regressing measurements against time. PIRATE can also be used to develop signal-pattern-recognition software for different purposes -- for example, to monitor and control manufacturing processes.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pierre, John W.; Wies, Richard; Trudnowski, Daniel
Time-synchronized measurements provide rich information for estimating a power-system's electromechanical modal properties via advanced signal processing. This information is becoming critical for the improved operational reliability of interconnected grids. A given mode's properties are described by its frequency, damping, and shape. Modal frequencies and damping are useful indicators of power-system stress, usually declining with increased load or reduced grid capacity. Mode shape provides critical information for operational control actions. This project investigated many advanced techniques for power system identification from measured data focusing on mode frequency and damping ratio estimation. Investigators from the three universities coordinated their effort with Pacificmore » Northwest National Laboratory (PNNL). Significant progress was made on developing appropriate techniques for system identification with confidence intervals and testing those techniques on field measured data and through simulation. Experimental data from the western area power system was provided by PNNL and Bonneville Power Administration (BPA) for both ambient conditions and for signal injection tests. Three large-scale tests were conducted for the western area in 2005 and 2006. Measured field PMU (Phasor Measurement Unit) data was provided to the three universities. A 19-machine simulation model was enhanced for testing the system identification algorithms. Extensive simulations were run with this model to test the performance of the algorithms. University of Wyoming researchers participated in four primary activities: (1) Block and adaptive processing techniques for mode estimation from ambient signals and probing signals, (2) confidence interval estimation, (3) probing signal design and injection method analysis, and (4) performance assessment and validation from simulated and field measured data. Subspace based methods have been use to improve previous results from block processing techniques. Bootstrap techniques have been developed to estimate confidence intervals for the electromechanical modes from field measured data. Results were obtained using injected signal data provided by BPA. A new probing signal was designed that puts more strength into the signal for a given maximum peak to peak swing. Further simulations were conducted on a model based on measured data and with the modifications of the 19-machine simulation model. Montana Tech researchers participated in two primary activities: (1) continued development of the 19-machine simulation test system to include a DC line; and (2) extensive simulation analysis of the various system identification algorithms and bootstrap techniques using the 19 machine model. Researchers at the University of Alaska-Fairbanks focused on the development and testing of adaptive filter algorithms for mode estimation using data generated from simulation models and on data provided in collaboration with BPA and PNNL. There efforts consist of pre-processing field data, testing and refining adaptive filter techniques (specifically the Least Mean Squares (LMS), the Adaptive Step-size LMS (ASLMS), and Error Tracking (ET) algorithms). They also improved convergence of the adaptive algorithms by using an initial estimate from block processing AR method to initialize the weight vector for LMS. Extensive testing was performed on simulated data from the 19 machine model. This project was also extensively involved in the WECC (Western Electricity Coordinating Council) system wide tests carried out in 2005 and 2006. These tests involved injecting known probing signals into the western power grid. One of the primary goals of these tests was the reliable estimation of electromechanical mode properties from measured PMU data. Applied to the system were three types of probing inputs: (1) activation of the Chief Joseph Dynamic Brake, (2) mid-level probing at the Pacific DC Intertie (PDCI), and (3) low-level probing on the PDCI. The Chief Joseph Dynamic Brake is a 1400 MW disturbance to the system and is injected for a half of a second. For the mid and low-level probing, the Celilo terminal of the PDCI is modulated with a known probing signal. Similar but less extensive tests were conducted in June of 2000. The low-level probing signals were designed at the University of Wyoming. A number of important design factors are considered. The designed low-level probing signal used in the tests is a multi-sine signal. Its frequency content is focused in the range of the inter-area electromechanical modes. The most frequently used of these low-level multi-sine signals had a period of over two minutes, a root-mean-square (rms) value of 14 MW, and a peak magnitude of 20 MW. Up to 15 cycles of this probing signal were injected into the system resulting in a processing gain of 15. The resulting measured response at points throughout the system was not much larger than the ambient noise present in the measurements.« less
Marchan-Hernandez, Juan Fernando; Camps, Adriano; Rodriguez-Alvarez, Nereida; Bosch-Lluis, Xavier; Ramos-Perez, Isaac; Valencia, Enric
2008-01-01
Signals from Global Navigation Satellite Systems (GNSS) were originally conceived for position and speed determination, but they can be used as signals of opportunity as well. The reflection process over a given surface modifies the properties of the scattered signal, and therefore, by processing the reflected signal, relevant geophysical data regarding the surface under study (land, sea, ice…) can be retrieved. In essence, a GNSS-R receiver is a multi-channel GNSS receiver that computes the received power from a given satellite at a number of different delay and Doppler bins of the incoming signal. The first approaches to build such a receiver consisted of sampling and storing the scattered signal for later post-processing. However, a real-time approach to the problem is desirable to obtain immediately useful geophysical variables and reduce the amount of data. The use of FPGA technology makes this possible, while at the same time the system can be easily reconfigured. The signal tracking and processing constraints made necessary to fully design several new blocks. The uniqueness of the implemented system described in this work is the capability to compute in real-time Delay-Doppler maps (DDMs) either for four simultaneous satellites or just one, but with a larger number of bins. The first tests have been conducted from a cliff over the sea and demonstrate the successful performance of the instrument to compute DDMs in real-time from the measured reflected GNSS/R signals. The processing of these measurements shall yield quantitative relationships between the sea state (mainly driven by the surface wind and the swell) and the overall DDM shape. The ultimate goal is to use the DDM shape to correct the sea state influence on the L-band brightness temperature to improve the retrieval of the sea surface salinity (SSS). PMID:27879862
Hwang, Hwan-Jin; Jung, Tae Woo; Hong, Ho Cheol; Choi, Hae Yoon; Seo, Ji-A; Kim, Sin Gon; Kim, Nan Hee; Choi, Kyung Mook; Choi, Dong Seop; Baik, Sei Hyun; Yoo, Hye Jin
2013-01-01
Atherosclerosis is considered a chronic inflammatory disease, initiated by activation and dysfunction of the endothelium. Recently, progranulin has been regarded as an important modulator of inflammatory processes; however, the role for prgranulin in regulating inflammation in vascular endothelial cells has not been described. Signaling pathways mediated by progranulin were analyzed in human umbilical vein endothelial cells (HUVECs) treated with progranulin. Progranulin significantly induced Akt and endothelial nitric oxide synthase (eNOS) phosphorylation in HUVECs, an effect that was blocked with Akt inhibitor. Furthermore, nitric oxide (NO) level, the end product of Akt/eNOS pathway, was significantly upregulated after progranulin treatment. Next, we showed that progranulin efficiently inhibited lipopolysaccharide (LPS)-mediated pro-inflammatory signaling. LPS-induced phosphorylation of IκB and nuclear factor-κB (NF-κB) levels decreased after progranulin treatment. Also, progranulin blocked translocation of NF-κB from the cytosol to the nucleus. In addition, progranulin significantly reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) by inhibiting binding of NF- κB to their promoter regions and blocked attachment of monocytes to HUVECs. Progranulin also significantly reduced the expression of tumor necrosis factor receptor-α (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1), the crucial inflammatory molecules known to aggravate atherosclerosis. Progranulin efficiently inhibited LPS-mediated pro-inflammatory signaling in endothelial cells through activation of the Akt/eNOS pathway and attenuation of the NF-κB pathway, suggesting its protective roles in vascular endothelium against inflammatory reaction underlying atherosclerosis.
Low Temperature Performance of High-Speed Neural Network Circuits
NASA Technical Reports Server (NTRS)
Duong, T.; Tran, M.; Daud, T.; Thakoor, A.
1995-01-01
Artificial neural networks, derived from their biological counterparts, offer a new and enabling computing paradigm specially suitable for such tasks as image and signal processing with feature classification/object recognition, global optimization, and adaptive control. When implemented in fully parallel electronic hardware, it offers orders of magnitude speed advantage. Basic building blocks of the new architecture are the processing elements called neurons implemented as nonlinear operational amplifiers with sigmoidal transfer function, interconnected through weighted connections called synapses implemented using circuitry for weight storage and multiply functions either in an analog, digital, or hybrid scheme.
Statistical Analysis of Adaptive Beam-Forming Methods
1988-05-01
minimum amount of computing resources? * What are the tradeoffs being made when a system design selects block averaging over exponential averaging? Will...understood by many signal processing practitioners, however, is how system parameters and the number of sensors effect the distribution of the... system performance improve and if so by how much? b " It is well known that the noise sampled at adjacent sensors is not statistically independent
Roadmap on semiconductor-cell biointerfaces
NASA Astrophysics Data System (ADS)
Tian, Bozhi; Xu, Shuai; Rogers, John A.; Cestellos-Blanco, Stefano; Yang, Peidong; Carvalho-de-Souza, João L.; Bezanilla, Francisco; Liu, Jia; Bao, Zhenan; Hjort, Martin; Cao, Yuhong; Melosh, Nicholas; Lanzani, Guglielmo; Benfenati, Fabio; Galli, Giulia; Gygi, Francois; Kautz, Rylan; Gorodetsky, Alon A.; Kim, Samuel S.; Lu, Timothy K.; Anikeeva, Polina; Cifra, Michal; Krivosudský, Ondrej; Havelka, Daniel; Jiang, Yuanwen
2018-05-01
This roadmap outlines the role semiconductor-based materials play in understanding the complex biophysical dynamics at multiple length scales, as well as the design and implementation of next-generation electronic, optoelectronic, and mechanical devices for biointerfaces. The roadmap emphasizes the advantages of semiconductor building blocks in interfacing, monitoring, and manipulating the activity of biological components, and discusses the possibility of using active semiconductor-cell interfaces for discovering new signaling processes in the biological world.
NASA Astrophysics Data System (ADS)
Haemisch, York; Frach, Thomas; Degenhardt, Carsten; Thon, Andreas
Silicon Photomultipliers (SiPMs) have emerged as promising alternative to fast vacuum photomultiplier tubes (PMT). A fully digital implementation of the Silicon Photomultiplier (dSiPM) has been developed in order to overcome the deficiencies and limitations of the so far only analog SiPMs (aSiPMs). Our sensor is based on arrays of single photon avalanche photodiodes (SPADs) integrated in a standard CMOS process. Photons are detected directly by sensing the voltage at the SPAD anode using a dedicated cell electronics block next to each diode. This block also contains active quenching and recharge circuits as well as a one bit memory for the selective inhibit of detector cells. A balanced trigger network is used to propagate the trigger signal from all cells to the integrated time-to-digital converter. In consequence, photons are detected and counted as digital signals, thus making the sensor less susceptible to temperature variations and electronic noise. The integration with CMOS logic provides the added benefit of low power consumption and possible integration of data post-processing directly in the sensor. In this overview paper, we discuss the sensor architecture together with its characteristics with a focus on scalability and practicability aspects for applications in medical imaging, high energy- and astrophysics.
Grb2 regulates B-cell maturation, B-cell memory responses and inhibits B-cell Ca2+ signalling.
Ackermann, Jochen A; Radtke, Daniel; Maurberger, Anna; Winkler, Thomas H; Nitschke, Lars
2011-04-20
Grb2 is a ubiquitously expressed adaptor protein, which activates Ras and MAP kinases in growth factor receptor signalling, while in B-cell receptor (BCR) signalling this role is controversial. In B cell lines it was shown that Grb2 can inhibit BCR-induced Ca(2+) signalling. Nonetheless, the physiological role of Grb2 in primary B cells is still unknown. We generated a B-cell-specific Grb2-deficient mouse line, which had a severe reduction of mature follicular B cells in the periphery due to a differentiation block and decreased B-cell survival. Moreover, we found several changes in important signalling pathways: enhanced BCR-induced Ca(2+) signalling, alterations in mitogen-activated protein kinase activation patterns and strongly impaired Akt activation, the latter pointing towards a defect in PI3K signalling. Interestingly, B-cell-specific Grb2-deficient mice showed impaired IgG and B-cell memory responses, and impaired germinal centre formation. Thus, Grb2-dependent signalling pathways are crucial for lymphocyte differentiation processes, as well as for control of secondary humoral immune responses.
Riding the Waves: How Our Cells Send Signals | Center for Cancer Research
The ability of cells to perceive and respond to their environment is critical in order to maintain basic cellular functions such as development, tissue repair, and response to stress. This process happens through a complex system of communication, called cell signaling, which governs basic cellular activities and coordinates cell actions. Errors in cell signaling have been linked to numerous diseases, including cancer. NF-κB is a protein complex that plays a critical role in many cell signaling pathways by controlling gene activation. It is widely used by cells to regulate cell growth and survival and helps to protect the cell from conditions that would otherwise cause it to die. Many tumor cells have mutations in genes that cause NF-κB to become overactive. Blocking NF-κB could cause tumor cells to stop growing, die, or become more sensitive to therapeutics.
BMP signaling is required for development of the ciliary body.
Zhao, Shulei; Chen, Qin; Hung, Fang-Cheng; Overbeek, Paul A
2002-10-01
The ciliary body in the eye secretes aqueous humor and glycoproteins of the vitreous body and maintains the intraocular pressure. The ciliary muscle controls the shape of the lens through the ciliary zonules to focus the image onto the retina. During embryonic development, the ciliary epithelium is derived from the optic vesicle, but the molecular signals that control morphogenesis of the ciliary body are unknown. We report that lens-specific expression of a transgenic protein, Noggin, can block BMP signaling in the mouse eye and result in failure in formation of the ciliary processes. Co-expression of transgenic BMP7 restores normal development of the ciliary epithelium. Ectopic expression of Noggin also promotes differentiation of retinal ganglion cells. These results indicate that BMP signaling is required for development of the ciliary body and may also play a role in regulation of neuronal differentiation in the developing eye.
Weak correlations between hemodynamic signals and ongoing neural activity during the resting state
Winder, Aaron T.; Echagarruga, Christina; Zhang, Qingguang; Drew, Patrick J.
2017-01-01
Spontaneous fluctuations in hemodynamic signals in the absence of a task or overt stimulation are used to infer neural activity. We tested this coupling by simultaneously measuring neural activity and changes in cerebral blood volume (CBV) in the somatosensory cortex of awake, head-fixed mice during periods of true rest, and during whisker stimulation and volitional whisking. Here we show that neurovascular coupling was similar across states, and large spontaneous CBV changes in the absence of sensory input were driven by volitional whisker and body movements. Hemodynamic signals during periods of rest were weakly correlated with neural activity. Spontaneous fluctuations in CBV and vessel diameter persisted when local neural spiking and glutamatergic input was blocked, and during blockade of noradrenergic receptors, suggesting a non-neuronal origin for spontaneous CBV fluctuations. Spontaneous hemodynamic signals reflect a combination of behavior, local neural activity, and putatively non-neural processes. PMID:29184204
Weak correlations between hemodynamic signals and ongoing neural activity during the resting state.
Winder, Aaron T; Echagarruga, Christina; Zhang, Qingguang; Drew, Patrick J
2017-12-01
Spontaneous fluctuations in hemodynamic signals in the absence of a task or overt stimulation are used to infer neural activity. We tested this coupling by simultaneously measuring neural activity and changes in cerebral blood volume (CBV) in the somatosensory cortex of awake, head-fixed mice during periods of true rest and during whisker stimulation and volitional whisking. We found that neurovascular coupling was similar across states and that large, spontaneous CBV changes in the absence of sensory input were driven by volitional whisker and body movements. Hemodynamic signals during periods of rest were weakly correlated with neural activity. Spontaneous fluctuations in CBV and vessel diameter persisted when local neural spiking and glutamatergic input were blocked, as well as during blockade of noradrenergic receptors, suggesting a non-neuronal origin for spontaneous CBV fluctuations. Spontaneous hemodynamic signals reflect a combination of behavior, local neural activity, and putatively non-neural processes.
Functional relationship-based alarm processing system
Corsberg, D.R.
1988-04-22
A functional relationship-based alarm processing system and method analyzes each alarm as it is activated and determines its relative importance with other currently activated alarms and signals in accordance with the functional relationships that the newly activated alarm has with other currently activated alarms. Once the initial level of importance of the alarm has been determined, that alarm is again evaluated if another related alarm is activated or deactivated. Thus, each alarm's importance is continuously updated as the state of the process changes during a scenario. Four hierarchical relationships are defined by this alarm filtering methodology: (1) level precursor (usually occurs when there are two alarm settings on the same parameter); (2) direct precursor (based on causal factors between two alarms); (3) required action (system response or action expected within a specified time following activation of an alarm or combination of alarms and process signals); and (4) blocking condition (alarms that are normally expected and are not considered important). The alarm processing system and method is sensitive to the dynamic nature of the process being monitored and is capable of changing the relative importance of each alarm as necessary. 12 figs.
Functional relationship-based alarm processing
Corsberg, Daniel R.
1988-01-01
A functional relationship-based alarm processing system and method analyzes each alarm as it is activated and determines its relative importance with other currently activated alarms and signals in accordance with the relationships that the newly activated alarm has with other currently activated alarms. Once the initial level of importance of the alarm has been determined, that alarm is again evaluated if another related alarm is activated. Thus, each alarm's importance is continuously oupdated as the state of the process changes during a scenario. Four hierarchical relationships are defined by this alarm filtering methodology: (1) level precursor (usually occurs when there are two alarm settings on the same parameter); (2) direct precursor (based on caussal factors between two alarms); (3) required action (system response or action) expected within a specified time following activation of an alarm or combination of alarms and process signals); and (4) blocking condition (alarms that are normally expected and are not considered important). The alarm processing system and method is sensitive to the dynamic nature of the process being monitored and is capable of changing the relative importance of each alarm as necessary.
Functional relationship-based alarm processing system
Corsberg, Daniel R.
1989-01-01
A functional relationship-based alarm processing system and method analyzes each alarm as it is activated and determines its relative importance with other currently activated alarms and signals in accordance with the functional relationships that the newly activated alarm has with other currently activated alarms. Once the initial level of importance of the alarm has been determined, that alarm is again evaluated if another related alarm is activated or deactivated. Thus, each alarm's importance is continuously updated as the state of the process changes during a scenario. Four hierarchical relationships are defined by this alarm filtering methodology: (1) level precursor (usually occurs when there are two alarm settings on the same parameter); (2) direct precursor (based on causal factors between two alarms); (3) required action (system response or action expected within a specified time following activation of an alarm or combination of alarms and process signals); and (4) blocking condition (alarms that are normally expected and are not considered important). The alarm processing system and method is sensitive to the dynamic nature of the process being monitored and is capable of changing the relative importance of each alarm as necessary.
Lateva, Zoia C; McGill, Kevin C
2007-12-01
Motor-unit action potentials (MUAPs) with unstable satellite (late-latency) components are found in EMG signals from the brachioradialis muscles of normal subjects. We analyzed the morphology and blocking behavior of these MUAPs to determine their anatomical origin. EMG signals were recorded from the brachioradialis muscles of 5 normal subjects during moderate-level isometric contractions. MUAP waveforms, discharge patterns, and blocking were determined using computer-aided EMG decomposition. Twelve MUAPs with unstable satellite potentials were detected, always two together in the same signal. Each MUAP also had a second unstable component associated with its main spike. The blocking behavior of the unstable components depended on how close together the two MUAPs were when they discharged. The latencies and blocking behavior indicate that the unstable components came from branched muscle fibers innervated by two different motoneurons. The satellite potentials were due to action potentials that traveled to the branching point along one branch and back along the other. The blockings were due to action-potential collisions when both motoneurons discharged close together in time. Animal studies suggest that branched muscle fibers may be a normal characteristic of series-fibered muscles. This study adds to our understanding of these muscles in humans.
A Signal Processing Module for the Analysis of Heart Sounds and Heart Murmurs
NASA Astrophysics Data System (ADS)
Javed, Faizan; Venkatachalam, P. A.; H, Ahmad Fadzil M.
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 & 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.
The Polerovirus silencing suppressor P0 targets ARGONAUTE proteins for degradation.
Baumberger, Nicolas; Tsai, Ching-Hsui; Lie, Miranda; Havecker, Ericka; Baulcombe, David C
2007-09-18
Plant and animal viruses encode suppressor proteins of an adaptive immunity mechanism in which viral double-stranded RNA is processed into 21-25 nt short interfering (si)RNAs. The siRNAs guide ARGONAUTE (AGO) proteins so that they target viral RNA. Most viral suppressors bind long dsRNA or siRNAs and thereby prevent production of siRNA or binding of siRNA to AGO. The one exception is the 2b suppressor of Cucumoviruses that binds to and inhibits AGO1. Here we describe a novel suppressor mechanism in which a Polerovirus-encoded F box protein (P0) targets the PAZ motif and its adjacent upstream sequence in AGO1 and mediates its degradation. F box proteins are components of E3 ubiquitin ligase complexes that add polyubiquitin tracts on selected lysine residues and thereby mark a protein for proteasome-mediated degradation. With P0, however, the targeted degradation of AGO is insensitive to inhibition of the proteasome, indicating that the proteasome is not involved. We also show that P0 does not block a mobile signal of silencing, indicating that the signal molecule does not have AGO protein components. The ability of P0 to block silencing without affecting signal movement may contribute to the phloem restriction of viruses in the Polerovirus group.
Attentional influences on functional mapping of speech sounds in human auditory cortex.
Obleser, Jonas; Elbert, Thomas; Eulitz, Carsten
2004-07-21
The speech signal contains both information about phonological features such as place of articulation and non-phonological features such as speaker identity. These are different aspects of the 'what'-processing stream (speaker vs. speech content), and here we show that they can be further segregated as they may occur in parallel but within different neural substrates. Subjects listened to two different vowels, each spoken by two different speakers. During one block, they were asked to identify a given vowel irrespectively of the speaker (phonological categorization), while during the other block the speaker had to be identified irrespectively of the vowel (speaker categorization). Auditory evoked fields were recorded using 148-channel magnetoencephalography (MEG), and magnetic source imaging was obtained for 17 subjects. During phonological categorization, a vowel-dependent difference of N100m source location perpendicular to the main tonotopic gradient replicated previous findings. In speaker categorization, the relative mapping of vowels remained unchanged but sources were shifted towards more posterior and more superior locations. These results imply that the N100m reflects the extraction of abstract invariants from the speech signal. This part of the processing is accomplished in auditory areas anterior to AI, which are part of the auditory 'what' system. This network seems to include spatially separable modules for identifying the phonological information and for associating it with a particular speaker that are activated in synchrony but within different regions, suggesting that the 'what' processing can be more adequately modeled by a stream of parallel stages. The relative activation of the parallel processing stages can be modulated by attentional or task demands.
Sequence information signal processor for local and global string comparisons
Peterson, John C.; Chow, Edward T.; Waterman, Michael S.; Hunkapillar, Timothy J.
1997-01-01
A sequence information signal processing integrated circuit chip designed to perform high speed calculation of a dynamic programming algorithm based upon the algorithm defined by Waterman and Smith. The signal processing chip of the present invention is designed to be a building block of a linear systolic array, the performance of which can be increased by connecting additional sequence information signal processing chips to the array. The chip provides a high speed, low cost linear array processor that can locate highly similar global sequences or segments thereof such as contiguous subsequences from two different DNA or protein sequences. The chip is implemented in a preferred embodiment using CMOS VLSI technology to provide the equivalent of about 400,000 transistors or 100,000 gates. Each chip provides 16 processing elements, and is designed to provide 16 bit, two's compliment operation for maximum score precision of between -32,768 and +32,767. It is designed to provide a comparison between sequences as long as 4,194,304 elements without external software and between sequences of unlimited numbers of elements with the aid of external software. Each sequence can be assigned different deletion and insertion weight functions. Each processor is provided with a similarity measure device which is independently variable. Thus, each processor can contribute to maximum value score calculation using a different similarity measure.
Puppo, A.; Chun, Jong T.; Gragnaniello, Giovanni; Garante, Ezio; Santella, Luigia
2008-01-01
Background When preparing for fertilization, oocytes undergo meiotic maturation during which structural changes occur in the endoplasmic reticulum (ER) that lead to a more efficient calcium response. During meiotic maturation and subsequent fertilization, the actin cytoskeleton also undergoes dramatic restructuring. We have recently observed that rearrangements of the actin cytoskeleton induced by actin-depolymerizing agents, or by actin-binding proteins, strongly modulate intracellular calcium (Ca2+) signals during the maturation process. However, the significance of the dynamic changes in F-actin within the fertilized egg has been largely unclear. Methodology/Principal Findings We have measured changes in intracellular Ca2+ signals and F-actin structures during fertilization. We also report the unexpected observation that the conventional antagonist of the InsP3 receptor, heparin, hyperpolymerizes the cortical actin cytoskeleton in postmeiotic eggs. Using heparin and other pharmacological agents that either hypo- or hyperpolymerize the cortical actin, we demonstrate that nearly all aspects of the fertilization process are profoundly affected by the dynamic restructuring of the egg cortical actin cytoskeleton. Conclusions/Significance Our findings identify important roles for subplasmalemmal actin fibers in the process of sperm-egg interaction and in the subsequent events related to fertilization: the generation of Ca2+ signals, sperm penetration, cortical granule exocytosis, and the block to polyspermy. PMID:18974786
Performance of greenhouse gas profiling by infrared-laser and microwave occultation in cloudy air
NASA Astrophysics Data System (ADS)
Proschek, V.; Kirchengast, G.; Emde, C.; Schweitzer, S.
2012-12-01
ACCURATE is a proposed future satellite mission enabling simultaneous measurements of greenhouse gases (GHGs), wind and thermodynamic variables from Low Earth Orbit (LEO). The measurement principle is a combination of LEO-LEO infrared-laser occultation (LIO) and microwave occultation (LMO), the LMIO method, where the LIO signals are very sensitive to clouds. The GHG retrieval will therefore be strongly influenced by clouds in parts of the troposphere. The IR-laser signals, at wavelengths within 2--2.5μ m, are chosen to measure six GHGs (H2O, CO2, CH4, N2O, O3, CO; incl.~key isotopes 13CO2, C18OO, HDO). The LMO signals enable to co-measure the thermodynamic variables. In this presentation we introduce the algorithm to retrieve GHG profiles under cloudy-air conditions by using quasi-realistic forward simulations, including also influence of Rayleigh scattering, scintillations and aerosols. Data from CALIPSO--Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations--with highest vertical resolution of about 60 m and horizontal resolution of about 330 m were used for simulation of clouds. The IR-laser signals consist for each GHG of a GHG-sensitive and a close-by reference signal. The key process, ``differencing'' of these two signals, removes the atmospheric ``broadband'' effects, resulting in a pure GHG transmission profile. Very thin ice clouds, like sub-visible cirrus, are fairly transparent to the IR-laser signals, thicker and liquid water clouds block the signals. The reference signal is used to produce a cloud layering profile from zero to blocking clouds and is smoothed in a preprocess to suppress scintillations. Sufficiently small gaps, of width <2 km in the cloud layering profile, are found to enable a decent retrieval of entire GHG profiles over the UTLS under broken cloudiness and are therefore bridged by interpolation. Otherwise in case of essentially continuous cloudiness the profiles are found to terminate at cloud top level. The accuracy of retrieved GHG profiles is found better than 1% to 4% for single profiles in the UTLS region outside clouds and through broken cloudiness, and the profiles are essentially unbiased. Cloud gap-interpolation increases the tropospheric penetration of GHG profiles for scientific applications. The associated cloud layering profile provides quality-control information on cloud gap-interpolations, if they occured, and on cloud-top altitude for cloud blocking cases. The LMIO technique shows promising prospects for GHG monitoring even under cloudy-air conditions.
Wang, Huayang; Cheng, Huanhuan; Shao, Qianqian; Dong, Zhaogang; Xie, Qi; Zhao, Lei; Wang, Qingjie; Kong, Beihua; Qu, Xun
2014-04-01
The overexpression of leptin is a crucial feature for the maintenance of pregnancy. The effects of leptin on trophoblast invasion are important to its reproductive function, but the underlying mechanisms remain poorly understood. MMP14 is a member of matrix metalloproteinase (MMP) family that is closely involved in the invasion process. Here, we characterized the importance of MMP14 in the proinvasion effect of leptin on EVT cells and elucidated its molecular mechanisms. Transwell assay revealed that leptin promoted invasion of the immortalized EVT cell line HTR-8/SVneo in a dose- and time-related fashion. Further studies suggested that leptin enhanced HTR-8/SVneo cell invasion by up-regulating MMP14 expression and that knockdown of MMP14 by small interference RNA (siRNA) blocked the proinvasion effect of leptin. Notably, leptin promoted the expression of Notch1 receptor and activated its signaling in HTR-8/SVneo cells, and blocking this pathway by siRNA inhibited both leptin-enhanced MMP14 expression and invasiveness of HTR-8/SVneo cells. Such effects of Notch1 signaling were related with the activation of the PI3K/Akt pathway, which was significantly activated after leptin stimulation and was interfered by Notch1 signaling perturbation. Taken together, our observations suggest that leptin is an effective regulator of MMP14 expression, which consequently plays critical roles in invasion of EVT cells. The promoting effects of leptin on MMP14 require the cross talk between Notch1 and PI3K/Akt signaling pathways.
Parmodulins inhibit thrombus formation without inducing endothelial injury caused by vorapaxar.
Aisiku, Omozuanvbo; Peters, Christian G; De Ceunynck, Karen; Ghosh, Chandra C; Dilks, James R; Fustolo-Gunnink, Susanna F; Huang, Mingdong; Dockendorff, Chris; Parikh, Samir M; Flaumenhaft, Robert
2015-03-19
Protease-activated receptor-1 (PAR1) couples the coagulation cascade to platelet activation during myocardial infarction and to endothelial inflammation during sepsis. This receptor demonstrates marked signaling bias. Its activation by thrombin stimulates prothrombotic and proinflammatory signaling, whereas its activation by activated protein C (APC) stimulates cytoprotective and antiinflammatory signaling. A challenge in developing PAR1-targeted therapies is to inhibit detrimental signaling while sparing beneficial pathways. We now characterize a novel class of structurally unrelated small-molecule PAR1 antagonists, termed parmodulins, and compare the activity of these compounds to previously characterized compounds that act at the PAR1 ligand-binding site. We find that parmodulins target the cytoplasmic face of PAR1 without modifying the ligand-binding site, blocking signaling through Gαq but not Gα13 in vitro and thrombus formation in vivo. In endothelium, parmodulins inhibit prothrombotic and proinflammatory signaling without blocking APC-mediated pathways or inducing endothelial injury. In contrast, orthosteric PAR1 antagonists such as vorapaxar inhibit all signaling downstream of PAR1. Furthermore, exposure of endothelial cells to nanomolar concentrations of vorapaxar induces endothelial cell barrier dysfunction and apoptosis. These studies demonstrate how functionally selective antagonism can be achieved by targeting the cytoplasmic face of a G-protein-coupled receptor to selectively block pathologic signaling while preserving cytoprotective pathways. © 2015 by The American Society of Hematology.
Smart Sensing and Recognition Based on Models of Neural Networks
1990-11-15
9P-o ,yY-’. AD-A230 701 University of Pensylvania Philadelphia, PA 19104-6390 SMART SENSING AND RECOGNITION BASED ON MODELS OF NEURAL NETWORKS ... networks , photonic 1 implementations, nonlinear dynamical signal processing 9 ABSTRACT (Continue on reverse if necessary and identify by block number...not develop in isolation but in synergism with sensory organs and their feature forming networks . This means that development of artificial pattern
Estimation of Ocean and Seabed Parameters and Processes Using Low Frequency Acoustic Signals
2012-09-30
were recently acquired under the DURIP program. 3. Finite Element Modeling of wave propagation: Doctoral student, Hui- Kwan Kim, is modeling wave...Delaware), Kevin Smith (Naval Postgraduate School), Dr. James F. Lynch and Dr. Y.-T. Lin (Woods Hole Oceanographic Institution). Another graduate student...test was conducted in collaboration with ARL, UT (Preston Wilson, PI) in August, 2011 in Narragansett Bay and off Block Island. PhD student Hui- Kwan
III-V Semiconductor Optical Micro-Ring Resonators
NASA Astrophysics Data System (ADS)
Grover, Rohit; Absil, Philippe P.; Ibrahim, Tarek A.; Ho, Ping-Tong
2004-05-01
We describe the theory of optical ring resonators, and our work on GaAs-AlGaAs and GaInAsP-InP optical micro-ring resonators. These devices are promising building blocks for future all-optical signal processing and photonic logic circuits. Their versatility allows the fabrication of ultra-compact multiplexers/demultiplexers, optical channel dropping filters, lasers, amplifiers, and logic gates (to name a few), which will enable large-scale monolithic integration for optics.
Random Walk Graph Laplacian-Based Smoothness Prior for Soft Decoding of JPEG Images.
Liu, Xianming; Cheung, Gene; Wu, Xiaolin; Zhao, Debin
2017-02-01
Given the prevalence of joint photographic experts group (JPEG) compressed images, optimizing image reconstruction from the compressed format remains an important problem. Instead of simply reconstructing a pixel block from the centers of indexed discrete cosine transform (DCT) coefficient quantization bins (hard decoding), soft decoding reconstructs a block by selecting appropriate coefficient values within the indexed bins with the help of signal priors. The challenge thus lies in how to define suitable priors and apply them effectively. In this paper, we combine three image priors-Laplacian prior for DCT coefficients, sparsity prior, and graph-signal smoothness prior for image patches-to construct an efficient JPEG soft decoding algorithm. Specifically, we first use the Laplacian prior to compute a minimum mean square error initial solution for each code block. Next, we show that while the sparsity prior can reduce block artifacts, limiting the size of the overcomplete dictionary (to lower computation) would lead to poor recovery of high DCT frequencies. To alleviate this problem, we design a new graph-signal smoothness prior (desired signal has mainly low graph frequencies) based on the left eigenvectors of the random walk graph Laplacian matrix (LERaG). Compared with the previous graph-signal smoothness priors, LERaG has desirable image filtering properties with low computation overhead. We demonstrate how LERaG can facilitate recovery of high DCT frequencies of a piecewise smooth signal via an interpretation of low graph frequency components as relaxed solutions to normalized cut in spectral clustering. Finally, we construct a soft decoding algorithm using the three signal priors with appropriate prior weights. Experimental results show that our proposal outperforms the state-of-the-art soft decoding algorithms in both objective and subjective evaluations noticeably.
49 CFR 236.205 - Signal control circuits; requirements.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 49 Transportation 4 2011-10-01 2011-10-01 false Signal control circuits; requirements. 236.205..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.205 Signal control circuits; requirements. The circuits shall be so...
49 CFR 236.205 - Signal control circuits; requirements.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 4 2010-10-01 2010-10-01 false Signal control circuits; requirements. 236.205..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.205 Signal control circuits; requirements. The circuits shall be so...
49 CFR 236.205 - Signal control circuits; requirements.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 49 Transportation 4 2014-10-01 2014-10-01 false Signal control circuits; requirements. 236.205..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.205 Signal control circuits; requirements. The circuits shall be so...
49 CFR 236.205 - Signal control circuits; requirements.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 49 Transportation 4 2012-10-01 2012-10-01 false Signal control circuits; requirements. 236.205..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.205 Signal control circuits; requirements. The circuits shall be so...
49 CFR 236.205 - Signal control circuits; requirements.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 49 Transportation 4 2013-10-01 2013-10-01 false Signal control circuits; requirements. 236.205..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.205 Signal control circuits; requirements. The circuits shall be so...
NASA Technical Reports Server (NTRS)
Chen, C.; Sytkowski, A. J.
2001-01-01
Erythropoietin (Epo) stimulation of erythroid cells results in the activation of several kinases and a rapid induction of c-myc expression. Protein kinase C is necessary for Epo up-regulation of c-myc by promoting elongation at the 3'-end of exon 1. PKCepsilon mediates this signal. We now show that Epo triggers two signaling pathways to c-myc. Epo rapidly up-regulated Myc protein in BaF3-EpoR cells. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 blocked Myc up-regulation in a concentration-dependent manner but had no effect on the Epo-induced phosphorylation of ERK1 and ERK2. LY294002 also had no effect on Epo up-regulation of c-fos. MEK1 inhibitor PD98059 blocked both the c-myc and the c-fos responses to Epo. PD98059 and the PKC inhibitor H7 also blocked the phosphorylation of ERK1 and ERK2. PD98059 but not LY294002 inhibited Epo induction of ERK1 and ERK2 phosphorylation in normal erythroid cells. LY294002 blocked transcription of c-myc at exon 1. PD98059 had no effect on transcription from exon 1 but, rather, blocked Epo-induced c-myc elongation at the 3'-end of exon 1. These results identify two Epo signaling pathways to c-myc, one of which is PI3K-dependent operating on transcriptional initiation, whereas the other is mitogen-activated protein kinase-dependent operating on elongation.
A Fully Integrated Sensor SoC with Digital Calibration Hardware and Wireless Transceiver at 2.4 GHz
Kim, Dong-Sun; Jang, Sung-Joon; Hwang, Tae-Ho
2013-01-01
A single-chip sensor system-on-a-chip (SoC) that implements radio for 2.4 GHz, complete digital baseband physical layer (PHY), 10-bit sigma-delta analog-to-digital converter and dedicated sensor calibration hardware for industrial sensing systems has been proposed and integrated in a 0.18-μm CMOS technology. The transceiver's building block includes a low-noise amplifier, mixer, channel filter, receiver signal-strength indicator, frequency synthesizer, voltage-controlled oscillator, and power amplifier. In addition, the digital building block consists of offset quadrature phase-shift keying (OQPSK) modulation, demodulation, carrier frequency offset compensation, auto-gain control, digital MAC function, sensor calibration hardware and embedded 8-bit microcontroller. The digital MAC function supports cyclic redundancy check (CRC), inter-symbol timing check, MAC frame control, and automatic retransmission. The embedded sensor signal processing block consists of calibration coefficient calculator, sensing data calibration mapper and sigma-delta analog-to-digital converter with digital decimation filter. The sensitivity of the overall receiver and the error vector magnitude (EVM) of the overall transmitter are −99 dBm and 18.14%, respectively. The proposed calibration scheme has a reduction of errors by about 45.4% compared with the improved progressive polynomial calibration (PPC) method and the maximum current consumption of the SoC is 16 mA. PMID:23698271
Model based design introduction: modeling game controllers to microprocessor architectures
NASA Astrophysics Data System (ADS)
Jungwirth, Patrick; Badawy, Abdel-Hameed
2017-04-01
We present an introduction to model based design. Model based design is a visual representation, generally a block diagram, to model and incrementally develop a complex system. Model based design is a commonly used design methodology for digital signal processing, control systems, and embedded systems. Model based design's philosophy is: to solve a problem - a step at a time. The approach can be compared to a series of steps to converge to a solution. A block diagram simulation tool allows a design to be simulated with real world measurement data. For example, if an analog control system is being upgraded to a digital control system, the analog sensor input signals can be recorded. The digital control algorithm can be simulated with the real world sensor data. The output from the simulated digital control system can then be compared to the old analog based control system. Model based design can compared to Agile software develop. The Agile software development goal is to develop working software in incremental steps. Progress is measured in completed and tested code units. Progress is measured in model based design by completed and tested blocks. We present a concept for a video game controller and then use model based design to iterate the design towards a working system. We will also describe a model based design effort to develop an OS Friendly Microprocessor Architecture based on the RISC-V.
Zheng, Jialin; Ghorpade, Anuja; Niemann, Douglas; Cotter, Robin L.; Thylin, Michael R.; Epstein, Leon; Swartz, Jennifer M.; Shepard, Robin B.; Liu, Xiaojuan; Nukuna, Adeline; Gendelman, Howard E.
1999-01-01
Chemokine receptors pivotal for human immunodeficiency virus type 1 (HIV-1) infection in lymphocytes and macrophages (CCR3, CCR5, and CXCR4) are expressed on neural cells (microglia, astrocytes, and/or neurons). It is these cells which are damaged during progressive HIV-1 infection of the central nervous system. We theorize that viral coreceptors could effect neural cell damage during HIV-1-associated dementia (HAD) without simultaneously affecting viral replication. To these ends, we studied the ability of diverse viral strains to affect intracellular signaling and apoptosis of neurons, astrocytes, and monocyte-derived macrophages. Inhibition of cyclic AMP, activation of inositol 1,4,5-trisphosphate, and apoptosis were induced by diverse HIV-1 strains, principally in neurons. Virions from T-cell-tropic (T-tropic) strains (MN, IIIB, and Lai) produced the most significant alterations in signaling of neurons and astrocytes. The HIV-1 envelope glycoprotein, gp120, induced markedly less neural damage than purified virions. Macrophage-tropic (M-tropic) strains (ADA, JR-FL, Bal, MS-CSF, and DJV) produced the least neural damage, while 89.6, a dual-tropic HIV-1 strain, elicited intermediate neural cell damage. All T-tropic strain-mediated neuronal impairments were blocked by the CXCR4 antibody, 12G5. In contrast, the M-tropic strains were only partially blocked by 12G5. CXCR4-mediated neuronal apoptosis was confirmed in pure populations of rat cerebellar granule neurons and was blocked by HA1004, an inhibitor of calcium/calmodulin-dependent protein kinase II, protein kinase A, and protein kinase C. Taken together, these results suggest that progeny HIV-1 virions can influence neuronal signal transduction and apoptosis. This process occurs, in part, through CXCR4 and is independent of CD4 binding. T-tropic viruses that traffic in and out of the brain during progressive HIV-1 disease may play an important role in HAD neuropathogenesis. PMID:10482576
Arsenite suppression of BMP signaling in human keratinocytes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Phillips, Marjorie A.; Qin, Qin; Hu, Qin
2013-06-15
Arsenic, a human skin carcinogen, suppresses differentiation of cultured keratinocytes. Exploring the mechanism of this suppression revealed that BMP-6 greatly increased levels of mRNA for keratins 1 and 10, two of the earliest differentiation markers expressed, a process prevented by co-treatment with arsenite. BMP also stimulated, and arsenite suppressed, mRNA for FOXN1, an important transcription factor driving early keratinocyte differentiation. Keratin mRNAs increased slowly after BMP-6 addition, suggesting they are indirect transcriptional targets. Inhibition of Notch1 activation blocked BMP induction of keratins 1 and 10, while FOXN1 induction was largely unaffected. Supporting a requirement for Notch1 signaling in keratin induction,more » BMP increased levels of activated Notch1, which was blocked by arsenite. BMP also greatly decreased active ERK, while co-treatment with arsenite maintained active ERK. Inhibition of ERK signaling mimicked BMP by inducing keratin and FOXN1 mRNAs and by increasing active Notch1, effects blocked by arsenite. Of 6 dual-specificity phosphatases (DUSPs) targeting ERK, two were induced by BMP unless prevented by simultaneous exposure to arsenite and EGF. Knockdown of DUSP2 or DUSP14 using shRNAs greatly reduced FOXN1 and keratins 1 and 10 mRNA levels and their induction by BMP. Knockdown also decreased activated Notch1, keratin 1 and keratin 10 protein levels, both in the presence and absence of BMP. Thus, one of the earliest effects of BMP is induction of DUSPs, which increases FOXN1 transcription factor and activates Notch1, both required for keratin gene expression. Arsenite prevents this cascade by maintaining ERK signaling, at least in part by suppressing DUSP expression. - Highlights: • BMP induces FOXN1 transcription. • BMP induces DUSP2 and DUSP14, suppressing ERK activation. • Arsenite suppresses levels of phosphorylated Smad1/5 and FOXN1 and DUSP mRNA. • These actions rationalize arsenite suppression of keratinocyte differentiation.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dufour, Marc, E-mail: Marc.dufour@chuv.ch; Faes, Seraina, E-mail: Seraina.faes@chuv.ch; Dormond-Meuwly, Anne, E-mail: Anne.meuwly-Dormond@chuv.ch
Highlights: • PGE{sub 2} activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE{sub 2} induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE{sub 2} induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E{sub 2} (PGE{sub 2}) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE{sub 2} directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized.more » In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE{sub 2}-induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE{sub 2} increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE{sub 2} EP{sub 4} receptor was responsible for transducing the signal to mTORC1. Moreover, PGE{sub 2} increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE{sub 2}-induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE{sub 2} increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE{sub 2} mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth.« less
Soto-Quiros, Pablo
2015-01-01
This paper presents a parallel implementation of a kind of discrete Fourier transform (DFT): the vector-valued DFT. The vector-valued DFT is a novel tool to analyze the spectra of vector-valued discrete-time signals. This parallel implementation is developed in terms of a mathematical framework with a set of block matrix operations. These block matrix operations contribute to analysis, design, and implementation of parallel algorithms in multicore processors. In this work, an implementation and experimental investigation of the mathematical framework are performed using MATLAB with the Parallel Computing Toolbox. We found that there is advantage to use multicore processors and a parallel computing environment to minimize the high execution time. Additionally, speedup increases when the number of logical processors and length of the signal increase.
Inhibiting core fucosylation attenuates glucose-induced peritoneal fibrosis in rats.
Li, Longkai; Shen, Nan; Wang, Nan; Wang, Weidong; Tang, Qingzhu; Du, Xiangning; Carrero, Juan Jesus; Wang, Keping; Deng, Yiyao; Li, Zhitong; Lin, Hongli; Wu, Taihua
2018-06-01
Ultrafiltration failure is a major complication of long-term peritoneal dialysis, resulting in dialysis failure. Peritoneal fibrosis induced by continuous exposure to high glucose dialysate is the major contributor of ultrafiltration failure, for which there is no effective treatment. Overactivation of several signaling pathways, including transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) pathways, contribute to the development of peritoneal fibrosis. Therefore, simultaneously blocking multiple signaling pathways might be a potential novel method of treating peritoneal fibrosis. Previously, we showed that core fucosylation, an important posttranslational modification of the TGF-β1 receptors, can regulate the activation of TGF-β1 signaling in renal interstitial fibrosis. However, it remains unclear whether core fucosylation affects the progression of peritoneal fibrosis. Herein, we show that core fucosylation was enriched in the peritoneal membrane of rats accompanied by peritoneal fibrosis induced by a high glucose dialysate. Blocking core fucosylation dramatically attenuated peritoneal fibrosis in the rat model achieved by simultaneously inactivating the TGF-β1 and PDGF signaling pathways. Next the protective effects of blocking core fucosylation and imatinib (a selective PDGF receptor inhibitor) on peritoneal fibrosis were compared and found to exhibit a greater inhibitory effect over imatinib alone, suggesting that blocking activation of multiple signaling pathways may have superior inhibitory effects on the development of peritoneal fibrosis. Thus, core fucosylation is essential for the development of peritoneal fibrosis by regulating the activation of multiple signaling pathways. This may be a potential novel target for drug development to treat peritoneal fibrosis. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
49 CFR 236.201 - Track-circuit control of signals.
Code of Federal Regulations, 2011 CFR
2011-10-01
..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.201 Track-circuit control of signals. The control circuits for home... 49 Transportation 4 2011-10-01 2011-10-01 false Track-circuit control of signals. 236.201 Section...
49 CFR 236.201 - Track-circuit control of signals.
Code of Federal Regulations, 2010 CFR
2010-10-01
..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.201 Track-circuit control of signals. The control circuits for home... 49 Transportation 4 2010-10-01 2010-10-01 false Track-circuit control of signals. 236.201 Section...
Code of Federal Regulations, 2011 CFR
2011-10-01
... INSTRUCTIONS GOVERNING THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Train Stop, Train Control and Cab Signal Systems Standards... automatic cab signal system shall be arranged so that cab signals will be continuously controlled in...
49 CFR 236.202 - Signal governing movements over hand-operated switch.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 4 2010-10-01 2010-10-01 false Signal governing movements over hand-operated..., AND APPLIANCES Automatic Block Signal Systems Standards § 236.202 Signal governing movements over hand-operated switch. Signal governing movements over hand-operated switch in the facing direction shall display...
49 CFR 236.14 - Spring switch signal protection; requirements.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 49 Transportation 4 2012-10-01 2012-10-01 false Spring switch signal protection; requirements. 236... Rules and Instructions: All Systems General § 236.14 Spring switch signal protection; requirements. (a... track signaled for movements in only one direction through a spring switch in automatic block signal...
49 CFR 236.14 - Spring switch signal protection; requirements.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 4 2010-10-01 2010-10-01 false Spring switch signal protection; requirements. 236... Rules and Instructions: All Systems General § 236.14 Spring switch signal protection; requirements. (a... track signaled for movements in only one direction through a spring switch in automatic block signal...
49 CFR 236.14 - Spring switch signal protection; requirements.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 49 Transportation 4 2011-10-01 2011-10-01 false Spring switch signal protection; requirements. 236... Rules and Instructions: All Systems General § 236.14 Spring switch signal protection; requirements. (a... track signaled for movements in only one direction through a spring switch in automatic block signal...
49 CFR 236.14 - Spring switch signal protection; requirements.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 49 Transportation 4 2013-10-01 2013-10-01 false Spring switch signal protection; requirements. 236... Rules and Instructions: All Systems General § 236.14 Spring switch signal protection; requirements. (a... track signaled for movements in only one direction through a spring switch in automatic block signal...
49 CFR 236.14 - Spring switch signal protection; requirements.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 49 Transportation 4 2014-10-01 2014-10-01 false Spring switch signal protection; requirements. 236... Rules and Instructions: All Systems General § 236.14 Spring switch signal protection; requirements. (a... track signaled for movements in only one direction through a spring switch in automatic block signal...
Hwang, Hwan-Jin; Jung, Tae Woo; Hong, Ho Cheol; Choi, Hae Yoon; Seo, Ji-A; Kim, Sin Gon; Kim, Nan Hee; Choi, Kyung Mook; Choi, Dong Seop; Baik, Sei Hyun; Yoo, Hye Jin
2013-01-01
Objective Atherosclerosis is considered a chronic inflammatory disease, initiated by activation and dysfunction of the endothelium. Recently, progranulin has been regarded as an important modulator of inflammatory processes; however, the role for prgranulin in regulating inflammation in vascular endothelial cells has not been described. Method and Results Signaling pathways mediated by progranulin were analyzed in human umbilical vein endothelial cells (HUVECs) treated with progranulin. Progranulin significantly induced Akt and endothelial nitric oxide synthase (eNOS) phosphorylation in HUVECs, an effect that was blocked with Akt inhibitor. Furthermore, nitric oxide (NO) level, the end product of Akt/eNOS pathway, was significantly upregulated after progranulin treatment. Next, we showed that progranulin efficiently inhibited lipopolysaccharide (LPS)-mediated pro-inflammatory signaling. LPS-induced phosphorylation of IκB and nuclear factor-κB (NF-κB) levels decreased after progranulin treatment. Also, progranulin blocked translocation of NF-κB from the cytosol to the nucleus. In addition, progranulin significantly reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) by inhibiting binding of NF- κB to their promoter regions and blocked attachment of monocytes to HUVECs. Progranulin also significantly reduced the expression of tumor necrosis factor receptor-α (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1), the crucial inflammatory molecules known to aggravate atherosclerosis. Conclusion Progranulin efficiently inhibited LPS-mediated pro-inflammatory signaling in endothelial cells through activation of the Akt/eNOS pathway and attenuation of the NF-κB pathway, suggesting its protective roles in vascular endothelium against inflammatory reaction underlying atherosclerosis. PMID:24098801
47 CFR 27.15 - Geographic partitioning and spectrum disaggregation.
Code of Federal Regulations, 2010 CFR
2010-10-01
... licensees have agreed to a different signal level. (c) License term. The license term for a partitioned...) Except for WCS licensees holding authorizations for Block A in the 698-704 MHz and 728-734 MHz bands, Block B in the 704-710 MHz and 734-740 MHz bands, Block E in the 722-728 MHz band, Blocks C, C1, or C2...
A New Built-in Self Test Scheme for Phase-Locked Loops Using Internal Digital Signals
NASA Astrophysics Data System (ADS)
Kim, Youbean; Kim, Kicheol; Kim, Incheol; Kang, Sungho
Testing PLLs (phase-locked loops) is becoming an important issue that affects both time-to-market and production cost of electronic systems. Though a PLL is the most common mixed-signal building block, it is very difficult to test due to internal analog blocks and signals. In this paper, we propose a new PLL BIST (built-in self test) using the distorted frequency detector that uses only internal digital signals. The proposed BIST does not need to load any analog nodes of the PLL. Therefore, it provides an efficient defect-oriented structural test scheme, reduced area overhead, and improved test quality compared with previous approaches.
Comparison of block and event-related experimental designs in diffusion-weighted functional MRI.
Williams, Rebecca J; McMahon, Katie L; Hocking, Julia; Reutens, David C
2014-08-01
To compare diffusion-weighted functional magnetic resonance imaging (DfMRI), a novel alternative to the blood oxygenation level-dependent (BOLD) contrast, in a functional MRI experiment. Nine participants viewed contrast reversing (7.5 Hz) black-and-white checkerboard stimuli using block and event-related paradigms. DfMRI (b = 1800 mm/s(2)) and BOLD sequences were acquired. Four parameters describing the observed signal were assessed: percent signal change, spatial extent of the activation, the Euclidean distance between peak voxel locations, and the time-to-peak of the best fitting impulse response for different paradigms and sequences. The BOLD conditions showed a higher percent signal change relative to DfMRI; however, event-related DfMRI showed the strongest group activation (t = 21.23, P < 0.0005). Activation was more diffuse and spatially closer to the BOLD response for DfMRI when the block design was used. DfMRIevent showed the shortest TTP (4.4 ± 0.88 sec). The hemodynamic contribution to DfMRI may increase with the use of block designs. © 2013 Wiley Periodicals, Inc.
NASA Astrophysics Data System (ADS)
Wang, Lixia; Pei, Jihong; Xie, Weixin; Liu, Jinyuan
2018-03-01
Large-scale oceansat remote sensing images cover a big area sea surface, which fluctuation can be considered as a non-stationary process. Short-Time Fourier Transform (STFT) is a suitable analysis tool for the time varying nonstationary signal. In this paper, a novel ship detection method using 2-D STFT sea background statistical modeling for large-scale oceansat remote sensing images is proposed. First, the paper divides the large-scale oceansat remote sensing image into small sub-blocks, and 2-D STFT is applied to each sub-block individually. Second, the 2-D STFT spectrum of sub-blocks is studied and the obvious different characteristic between sea background and non-sea background is found. Finally, the statistical model for all valid frequency points in the STFT spectrum of sea background is given, and the ship detection method based on the 2-D STFT spectrum modeling is proposed. The experimental result shows that the proposed algorithm can detect ship targets with high recall rate and low missing rate.
A comparison of Manchester symbol tracking loops for block 5 applications
NASA Technical Reports Server (NTRS)
Holmes, J. K.
1991-01-01
The linearized tracking errors of three Manchester (biphase coded) symbol tracking loops are compared to determine which is appropriate for Block 5 receiver applications. The first is a nonreturn to zero (NRZ) symbol synchronizer loop operating at twice the symbol rate (NRZ x 2) so that it operates on half symbols. The second near optimally processes the mid-symbol transitions and ignores the between symbol transitions. In the third configuration, the first two approaches are combined as a hybrid to produce the best performance. Although this hybrid loop is the best at low symbol signal to noise ratios (SNRs), it has about the same performance as the NRZ x 2 loop at higher SNRs (greater than 0-dB E sub s/N sub 0). Based on this analysis, it is tentatively recommended that the hybrid loop be implemented for Manchester data in the Block 5 receiver. However, the high data rate case and the hardware implications of each implementation must be understood and analyzed before the hybrid loop is recommended unconditionally.
Neurexin and Neuroligin Mediate Retrograde Synaptic Inhibition in C. elegans
Hu, Zhitao; Hom, Sabrina; Kudze, Tambudzai; Tong, Xia-Jing; Choi, Seungwon; Aramuni, Gayane; Zhang, Weiqi; Kaplan, Joshua M.
2013-01-01
The synaptic adhesion molecules Neurexin and Neuroligin alter the development and function of synapses and are linked to autism in humans. We find that C. elegans Neurexin (NRX-1) and Neuroligin (NLG-1) mediate a retrograde synaptic signal that inhibits neurotransmitter release at neuromuscular junctions. Retrograde signaling was induced in mutants lacking a muscle microRNA (miR-1) and was blocked in mutants lacking NLG-1 or NRX-1. Release was rapid and abbreviated when the retrograde signal was on whereas release was slow and prolonged when retrograde signaling was blocked. The retrograde signal adjusted release kinetics by inhibiting exocytosis of synaptic vesicles (SVs) that are distal to the site of calcium entry. Inhibition of release was mediated by increased pre-synaptic levels of Tomosyn, an inhibitor of SV fusion. PMID:22859820
Mok, Sue-Ann; Lund, Karen; Campenot, Robert B
2009-05-01
Previous investigations of retrograde survival signaling by nerve growth factor (NGF) and other neurotrophins have supported diverse mechanisms, but all proposed mechanisms have in common the generation of survival signals retrogradely transmitted to the neuronal cell bodies. We report the finding of a retrograde apoptotic signal in axons that is suppressed by local NGF signaling. NGF withdrawal from distal axons alone was sufficient to activate the pro-apoptotic transcription factor, c-jun, in the cell bodies. Providing NGF directly to cell bodies, thereby restoring a source of NGF-induced survival signals, could not prevent c-jun activation caused by NGF withdrawal from the distal axons. This is evidence that c-jun is not activated due to loss of survival signals at the cell bodies. Moreover, blocking axonal transport with colchicine inhibited c-jun activation caused by NGF deprivation suggesting that a retrogradely transported pro-apoptotic signal, rather than loss of a retrogradely transported survival signal, caused c-jun activation. Additional experiments showed that activation of c-jun, pro-caspase-3 cleavage, and apoptosis were blocked by the protein kinase C inhibitors, rottlerin and chelerythrine, only when applied to distal axons suggesting that they block the axon-specific pro-apoptotic signal. The rottlerin-sensitive mechanism was found to regulate glycogen synthase kinase 3 (GSK3) activity. The effect of siRNA knockdown, and pharmacological inhibition of GSK3 suggests that GSK3 is required for apoptosis caused by NGF deprivation and may function as a retrograde carrier of the axon apoptotic signal. The existence of a retrograde death signaling system in axons that is suppressed by neurotrophins has broad implications for neurodevelopment and for discovering treatments for neurodegenerative diseases and neurotrauma.
Fast realization of nonrecursive digital filters with limits on signal delay
NASA Astrophysics Data System (ADS)
Titov, M. A.; Bondarenko, N. N.
1983-07-01
Attention is given to the problem of achieving a fast realization of nonrecursive digital filters with the aim of reducing signal delay. It is shown that a realization wherein the impulse characteristic of the filter is divided into blocks satisfies the delay requirements and is almost as economical in terms of the number of multiplications as conventional fast convolution. In addition, the block method leads to a reduction in the needed size of the memory and in the number of additions; the short-convolution procedure is substantially simplified. Finally, the block method facilitates the paralleling of computations owing to the simple transfers between subfilters.
Effects of specimen resonances on acoustic-ultrasonic testing
NASA Technical Reports Server (NTRS)
Williams, J. H., Jr.; Kahn, E. B.; Lee, S. S.
1983-01-01
The effects of specimen resonances on acoustic ultrasonic (AU) nondestructive testing were investigated. Selected resonant frequencies and the corresponding normal mode nodal patterns of the aluminum block are measured up to 75.64 kHz. Prominent peaks in the pencil lead fracture and sphere impact spectra from the two transducer locations corresponded exactly to resonant frequencies of the block. It is established that the resonant frequencies of the block dominated the spectral content of the output signal. The spectral content of the output signals is further influenced by the transducer location relative to the resonant frequency nodal lines. Implications of the results are discussed in relation to AU parameters and measurements.
Star-PAP Control of BIK Expression and Apoptosis Is Regulated by Nuclear PIPKIα and PKCδ Signaling
Li, Weimin; Laishram, Rakesh S.; Ji, Zhe; Barlow, Christy A.; Tian, Bin; Anderson, Richard A.
2012-01-01
SUMMARY BIK protein is an initiator of mitochondrial apoptosis and BIK expression is induced by pro-apoptotic signals including DNA damage. Here we demonstrate that 3′-end processing and expression of BIK mRNA are controlled by the nuclear PI4,5P2-regulated poly(A) polymerase Star-PAP downstream of DNA damage. Nuclear PKCδ is a key mediator of apoptosis and DNA damage stimulates PKCδ association with the Star-PAP complex where PKCδ is required for Star-PAP-dependent BIK expression. PKCδ binds the PI4,5P2-generating enzyme PIPKIα, which is essential for PKCδ interaction with the Star-PAP complex and PKCδ activity is directly stimulated by PI4,5P2. Features in the BIK 3′-UTR uniquely define Star-PAP specificity and may block canonical PAP activity toward BIK mRNA. This reveals a nuclear phosphoinositide signaling nexus where PIPKIα, PI4,5P2 and PKCδ regulate Star-PAP control of BIK expression and induction of apoptosis. This pathway is distinct from the Star-PAP-mediated oxidative stress pathway indicating signal-specific regulation of mRNA 3′-end processing. PMID:22244330
Guzmán, R; Carpintero, G; Gordon, C; Orbe, L
2016-10-15
We demonstrate and compare two different photonic-based signal sources for generating the carrier wave in a wireless communication link operating in the millimeter-wave range. The first signal source uses the optical heterodyne technique to generate a 113 GHz carrier wave frequency, while the second employs a different technique based on a pulsed mode-locked source with 100 GHz repetition rate frequency. The two optical sources were fabricated in a multi-project wafer run from an active/passive generic integration platform process using standardized building blocks, including multimode interference reflectors which allow us to define the structures on chip, without the need for cleaved facet mirrors. We highlight the superior performance of the mode-locked sources over an optical heterodyne technique. Error-free transmission was achieved in this experiment.
49 CFR 236.806 - Signal, home.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 49 Transportation 4 2013-10-01 2013-10-01 false Signal, home. 236.806 Section 236.806 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Signal, home. A roadway signal at the entrance to a route or block to govern trains in entering and using...
49 CFR 236.806 - Signal, home.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 49 Transportation 4 2012-10-01 2012-10-01 false Signal, home. 236.806 Section 236.806 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Signal, home. A roadway signal at the entrance to a route or block to govern trains in entering and using...
49 CFR 236.806 - Signal, home.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 4 2010-10-01 2010-10-01 false Signal, home. 236.806 Section 236.806 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Signal, home. A roadway signal at the entrance to a route or block to govern trains in entering and using...
49 CFR 236.806 - Signal, home.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 49 Transportation 4 2011-10-01 2011-10-01 false Signal, home. 236.806 Section 236.806 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Signal, home. A roadway signal at the entrance to a route or block to govern trains in entering and using...
49 CFR 236.806 - Signal, home.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 49 Transportation 4 2014-10-01 2014-10-01 false Signal, home. 236.806 Section 236.806 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Signal, home. A roadway signal at the entrance to a route or block to govern trains in entering and using...
Frequency domain measurement systems
NASA Technical Reports Server (NTRS)
Eischer, M. C.
1978-01-01
Stable frequency sources and signal processing blocks were characterized by their noise spectra, both discrete and random, in the frequency domain. Conventional measures are outlined, and systems for performing the measurements are described. Broad coverage of system configurations which were found useful is given. Their functioning and areas of application are discussed briefly. Particular attention is given to some of the potential error sources in the measurement procedures, system configurations, double-balanced-mixer-phase-detectors, and application of measuring instruments.
2008-12-09
as an antenna followed by an analog signal processing chain ( filters , RF amplifiers) followed by an analog-to- digital converter (ADC) followed by a...Figure 2.3 Block diagram of a DSP- based superheterodyne receiver. ADC RF Filter LNA IF Filter IF Amplifier Tunable Local Oscillator ADC...some band limiting filtering and amplification. In a more realistic architecture (Figure 2.3) that we call the DSP- based superheterodyne receiver, a
LANDSAT-D flight segment operations manual, volume 1
NASA Technical Reports Server (NTRS)
Varhola, J.
1982-01-01
Hardware, systems, and subsystems for the multimission modular spacecraft used for LANDSAT 4 are described and depicted in block diagrams and schematics. Components discussed include the modular attitude control system; the communication and data handling subsystem; the narrowband tape recorder; the on-board computer; the propulsion module subsystem; the signal conditioning and control unit; the modular power subsystem; the solar array drive and power transmission assembly; the power distribution unit; the digital processing unit; and the wideband communication subsystem.
KCl stimulation increases norepinephrine transporter function in PC12 cells.
Mandela, Prashant; Ordway, Gregory A
2006-09-01
The norepinephrine transporter (NET) plays a pivotal role in terminating noradrenergic signaling and conserving norepinephrine (NE) through the process of re-uptake. Recent evidence suggests a close association between NE release and regulation of NET function. The present study evaluated the relationship between release and uptake, and the cellular mechanisms that govern these processes. KCl stimulation of PC12 cells robustly increased [3H]NE uptake via the NET and simultaneously increased [3H]NE release. KCl-stimulated increases in uptake and release were dependent on Ca2+. Treatment of cells with phorbol-12-myristate-13-acetate (PMA) or okadaic acid decreased [3H]NE uptake but did not block KCl-stimulated increases in [3H]NE uptake. In contrast, PMA increased [3H]NE release and augmented KCl-stimulated release, while okadaic acid had no effects on release. Inhibition of Ca2+-activated signaling cascades with KN93 (a Ca2+ calmodulin-dependent kinase inhibitor), or ML7 and ML9 (myosin light chain kinase inhibitors), reduced [3H]NE uptake and blocked KCl-stimulated increases in uptake. In contrast, KN93, ML7 and ML9 had no effect on KCl-stimulated [3H]NE release. KCl-stimulated increases in [3H]NE uptake were independent of transporter trafficking to the plasma membrane. While increases in both NE release and uptake mediated by KCl stimulation require Ca2+, different intracellular mechanisms mediate these two events.
The GPS Burst Detector W-Sensor
DOE Office of Scientific and Technical Information (OSTI.GOV)
McCrady, D.D.; Phipps, P.
1994-08-01
The NAVSTAR satellites have two missions: navigation and nuclear detonation detection. The main objective of this paper is to describe one of the key elements of the Nuclear Detonation Detection System (NDS), the Burst Detector W-Sensor (BDW) that was developed for the Air Force Space and Missle Systems Center, its mission on GPS Block IIR, and how it utilizes GPS timing signals to precisely locate nuclear detonations (NUDET). The paper will also cover the interface to the Burst Detector Processor (BDP) which links the BDW to the ground station where the BDW is controlled and where data from multiple satellitesmore » are processed to determine the location of the NUDET. The Block IIR BDW is the culmination of a development program that has produced a state-of-the-art, space qualified digital receiver/processor that dissipates only 30 Watts, weighs 57 pounds, and has a 12in. {times} l4.2in. {times} 7.16in. footprint. The paper will highlight several of the key multilayer printed circuit cards without which the required power, weight, size, and radiation requirements could not have been met. In addition, key functions of the system software will be covered. The paper will be concluded with a discussion of the high speed digital signal processing and algorithm used to determine the time-of-arrival (TOA) of the electromagnetic pulse (EMP) from the NUDET.« less
Mitochondrial redox and pH signaling occurs in axonal and synaptic organelle clusters.
Breckwoldt, Michael O; Armoundas, Antonis A; Aon, Miguel A; Bendszus, Martin; O'Rourke, Brian; Schwarzländer, Markus; Dick, Tobias P; Kurz, Felix T
2016-03-22
Redox switches are important mediators in neoplastic, cardiovascular and neurological disorders. We recently identified spontaneous redox signals in neurons at the single mitochondrion level where transients of glutathione oxidation go along with shortening and re-elongation of the organelle. We now have developed advanced image and signal-processing methods to re-assess and extend previously obtained data. Here we analyze redox and pH signals of entire mitochondrial populations. In total, we quantified the effects of 628 redox and pH events in 1797 mitochondria from intercostal axons and neuromuscular synapses using optical sensors (mito-Grx1-roGFP2; mito-SypHer). We show that neuronal mitochondria can undergo multiple redox cycles exhibiting markedly different signal characteristics compared to single redox events. Redox and pH events occur more often in mitochondrial clusters (medium cluster size: 34.1 ± 4.8 μm(2)). Local clusters possess higher mitochondrial densities than the rest of the axon, suggesting morphological and functional inter-mitochondrial coupling. We find that cluster formation is redox sensitive and can be blocked by the antioxidant MitoQ. In a nerve crush paradigm, mitochondrial clusters form sequentially adjacent to the lesion site and oxidation spreads between mitochondria. Our methodology combines optical bioenergetics and advanced signal processing and allows quantitative assessment of entire mitochondrial populations.
Hetrick, Vaughn L.; Berke, Joshua D.
2017-01-01
The capacity for using external cues to guide behavior (“cue detection”) constitutes an essential aspect of attention and goal-directed behavior. The cortical cholinergic input system, via phasic increases in prefrontal acetylcholine release, plays an essential role in attention by mediating such cue detection. However, the relationship between cholinergic signaling during cue detection and neural activity dynamics in prefrontal networks remains unclear. Here we combined subsecond measures of cholinergic signaling, neurophysiological recordings, and cholinergic receptor blockade to delineate the cholinergic contributions to prefrontal oscillations during cue detection in rats. We first confirmed that detected cues evoke phasic acetylcholine release. These cholinergic signals were coincident with increased neuronal synchrony across several frequency bands and the emergence of theta–gamma coupling. Muscarinic and nicotinic cholinergic receptors both contributed specifically to gamma synchrony evoked by detected cues, but the effects of blocking the two receptor subtypes were dissociable. Blocking nicotinic receptors primarily attenuated high-gamma oscillations occurring during the earliest phases of the cue detection process, while muscarinic (M1) receptor activity was preferentially involved in the transition from high to low gamma power that followed and corresponded to the mobilization of networks involved in cue-guided decision making. Detected cues also promoted coupling between gamma and theta oscillations, and both nicotinic and muscarinic receptor activity contributed to this process. These results indicate that acetylcholine release coordinates neural oscillations during the process of cue detection. SIGNIFICANCE STATEMENT The capacity of learned cues to direct attention and guide responding (“cue detection”) is a key component of goal-directed behavior. Rhythmic neural activity and increases in acetylcholine release in the prefrontal cortex contribute to this process; however, the relationship between these neuronal mechanisms is not well understood. Using a combination of in vivo neurochemistry, neurophysiology, and pharmacological methods, we demonstrate that cue-evoked acetylcholine release, through distinct actions at both nicotinic and muscarinic receptors, triggers a procession of neural oscillations that map onto the multiple stages of cue detection. Our data offer new insights into cholinergic function by revealing the temporally orchestrated changes in prefrontal network synchrony modulated by acetylcholine release during cue detection. PMID:28213446
Discriminability limits in spatio-temporal stereo block matching.
Jain, Ankit K; Nguyen, Truong Q
2014-05-01
Disparity estimation is a fundamental task in stereo imaging and is a well-studied problem. Recently, methods have been adapted to the video domain where motion is used as a matching criterion to help disambiguate spatially similar candidates. In this paper, we analyze the validity of the underlying assumptions of spatio-temporal disparity estimation, and determine the extent to which motion aids the matching process. By analyzing the error signal for spatio-temporal block matching under the sum of squared differences criterion and treating motion as a stochastic process, we determine the probability of a false match as a function of image features, motion distribution, image noise, and number of frames in the spatio-temporal patch. This performance quantification provides insight into when spatio-temporal matching is most beneficial in terms of the scene and motion, and can be used as a guide to select parameters for stereo matching algorithms. We validate our results through simulation and experiments on stereo video.
Analog computation of auto and cross-correlation functions
NASA Technical Reports Server (NTRS)
1974-01-01
For analysis of the data obtained from the cross beam systems it was deemed desirable to compute the auto- and cross-correlation functions by both digital and analog methods to provide a cross-check of the analysis methods and an indication as to which of the two methods would be most suitable for routine use in the analysis of such data. It is the purpose of this appendix to provide a concise description of the equipment and procedures used for the electronic analog analysis of the cross beam data. A block diagram showing the signal processing and computation set-up used for most of the analog data analysis is provided. The data obtained at the field test sites were recorded on magnetic tape using wide-band FM recording techniques. The data as recorded were band-pass filtered by electronic signal processing in the data acquisition systems.
NASA Astrophysics Data System (ADS)
Bugiel, Sz.; Dasgupta, R.; Firlej, M.; Fiutowski, T.; Idzik, M.; Kuczynska, M.; Moron, J.; Swientek, K.; Szumlak, T.
2016-02-01
The Upstream Tracker (UT) silicon strip detector, one of the central parts of the tracker system of the modernised LHCb experiment, will use a new 128-channel readout ASIC called SALT. It will extract and digitise analogue signals from the UT sensors, perform digital signal processing and transmit a serial output data. The SALT is being designed in CMOS 130 nm process and uses a novel architecture comprising of analog front-end and fast (40 MSps) ultra-low power (<0.5 mW) 6-bit ADC in each channel. The prototype ASICs of important functional blocks, like analogue front-end, 6-bit SAR ADC, PLL, and DLL, were designed, fabricated and tested. A prototype of an 8-channel version of the SALT chip, comprising all important functionalities was also designed and fabricated. The architecture and design of the SALT, together with the selected preliminary tests results, are presented.
PI controller design for indirect vector controlled induction motor: A decoupling approach.
Jain, Jitendra Kr; Ghosh, Sandip; Maity, Somnath; Dworak, Pawel
2017-09-01
Decoupling of the stator currents is important for smoother torque response of indirect vector controlled induction motors. Typically, feedforward decoupling is used to take care of current coupling that requires exact knowledge of motor parameters, additional circuitry and signal processing. In this paper, a method is proposed to design the regulating proportional-integral gains that minimize coupling without any requirement of the additional decoupler. The variation of the coupling terms for change in load torque is considered as the performance measure. An iterative linear matrix inequality based H ∞ control design approach is used to obtain the controller gains. A comparison between the feedforward and the proposed decoupling schemes is presented through simulation and experimental results. The results show that the proposed scheme is simple yet effective even without additional block or burden on signal processing. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.
Biased Feedback in Spatial Recall Yields a Violation of Delta Rule Learning
Lipinski, John; Spencer, John P.; Samuelson, Larissa K.
2010-01-01
This study investigates whether inductive processes influencing spatial memory performance generalize to supervised learning scenarios with differential feedback. After providing a location memory response in a spatial recall task, participants received visual feedback showing the target location. In critical blocks, feedback was systematically biased either 4° towards the vertical axis (Towards condition) or 4° further away from the vertical axis (Away condition). Results showed that the weaker teaching signal (i.e., a smaller difference between the remembered location and the feedback location) in the Away condition produced a stronger experience-dependent change over blocks than in the Towards condition. This violates delta rule learning. Subsequent simulations of the Dynamic Field Theory of spatial cognition provide a theoretically unified account of these results. PMID:20702881
Biased feedback in spatial recall yields a violation of delta rule learning.
Lipinski, John; Spencer, John P; Samuelson, Larissa K
2010-08-01
This study investigates whether inductive processes influencing spatial memory performance generalize to supervised learning scenarios with differential feedback. After providing a location memory response in a spatial recall task, participants received visual feedback showing the target location. In critical blocks, feedback was systematically biased either 4 degrees toward the vertical axis (toward condition) or 4 degrees farther away from the vertical axis (away condition). Results showed that the weaker teaching signal (i.e., a smaller difference between the remembered location and the feedback location) produced a stronger experience-dependent change over blocks in the away condition than in the toward condition. This violates delta rule learning. Subsequent simulations of the dynamic field theory of spatial cognition provide a theoretically unified account of these results.
Duplicate laboratory test reduction using a clinical decision support tool.
Procop, Gary W; Yerian, Lisa M; Wyllie, Robert; Harrison, A Marc; Kottke-Marchant, Kandice
2014-05-01
Duplicate laboratory tests that are unwarranted increase unnecessary phlebotomy, which contributes to iatrogenic anemia, decreased patient satisfaction, and increased health care costs. We employed a clinical decision support tool (CDST) to block unnecessary duplicate test orders during the computerized physician order entry (CPOE) process. We assessed laboratory cost savings after 2 years and searched for untoward patient events associated with this intervention. This CDST blocked 11,790 unnecessary duplicate test orders in these 2 years, which resulted in a cost savings of $183,586. There were no untoward effects reported associated with this intervention. The movement to CPOE affords real-time interaction between the laboratory and the physician through CDSTs that signal duplicate orders. These interactions save health care dollars and should also increase patient satisfaction and well-being.
Pant, Jeevan K; Krishnan, Sridhar
2018-03-15
To present a new compressive sensing (CS)-based method for the acquisition of ECG signals and for robust estimation of heart-rate variability (HRV) parameters from compressively sensed measurements with high compression ratio. CS is used in the biosensor to compress the ECG signal. Estimation of the locations of QRS segments is carried out by applying two algorithms on the compressed measurements. The first algorithm reconstructs the ECG signal by enforcing a block-sparse structure on the first-order difference of the signal, so the transient QRS segments are significantly emphasized on the first-order difference of the signal. Multiple block-divisions of the signals are carried out with various block lengths, and multiple reconstructed signals are combined to enhance the robustness of the localization of the QRS segments. The second algorithm removes errors in the locations of QRS segments by applying low-pass filtering and morphological operations. The proposed CS-based method is found to be effective for the reconstruction of ECG signals by enforcing transient QRS structures on the first-order difference of the signal. It is demonstrated to be robust not only to high compression ratio but also to various artefacts present in ECG signals acquired by using on-body wireless sensors. HRV parameters computed by using the QRS locations estimated from the signals reconstructed with a compression ratio as high as 90% are comparable with that computed by using QRS locations estimated by using the Pan-Tompkins algorithm. The proposed method is useful for the realization of long-term HRV monitoring systems by using CS-based low-power wireless on-body biosensors.
A Synchronization Algorithm and Implementation for High-Speed Block Codes Applications. Part 4
NASA Technical Reports Server (NTRS)
Lin, Shu; Zhang, Yu; Nakamura, Eric B.; Uehara, Gregory T.
1998-01-01
Block codes have trellis structures and decoders amenable to high speed CMOS VLSI implementation. For a given CMOS technology, these structures enable operating speeds higher than those achievable using convolutional codes for only modest reductions in coding gain. As a result, block codes have tremendous potential for satellite trunk and other future high-speed communication applications. This paper describes a new approach for implementation of the synchronization function for block codes. The approach utilizes the output of the Viterbi decoder and therefore employs the strength of the decoder. Its operation requires no knowledge of the signal-to-noise ratio of the received signal, has a simple implementation, adds no overhead to the transmitted data, and has been shown to be effective in simulation for received SNR greater than 2 dB.
Morgan, Michael M.; Reid, Rachel A.; Saville, Kimber A.
2014-01-01
Functionally selective signaling appears to contribute to the variability in mechanisms that underlie tolerance to the antinociceptive effects of opioids. The present study tested this hypothesis by examining the contribution of G protein-coupled receptor kinase (GRK)/Protein kinase C (PKC) and C-Jun N-terminal kinase (JNK) activation on both the expression and development of tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray of the rat. Microinjection of morphine or fentanyl into the periaqueductal gray produced a dose-dependent increase in hot plate latency. Microinjection of the non-specific GRK/PKC inhibitor Ro 32-0432 into the periaqueductal gray to block mu-opioid receptor phosphorylation enhanced the antinociceptive effect of morphine but had no effect on fentanyl antinociception. Microinjection of the JNK inhibitor SP600125 had no effect on morphine or fentanyl antinociception, but blocked the expression of tolerance to repeated morphine microinjections. In contrast, a microinjection of Ro 32-0432 blocked the expression of fentanyl, but not morphine tolerance. Repeated microinjections of Ro 32-0432 blocked the development of morphine tolerance and inhibited fentanyl antinociception whether rats were tolerant or not. Repeated microinjections of SP600125 into the periaqueductal gray blocked the development of tolerance to both morphine and fentanyl microinjections. These data demonstrate that the signaling molecules that contribute to tolerance vary depending on the opioid and methodology used to assess tolerance (expression vs. development of tolerance). This signaling difference is especially clear for the expression of tolerance in which JNK contributes to morphine tolerance and GRK/PKC contributes to fentanyl tolerance. PMID:25503060
Evolutionary Fuzzy Block-Matching-Based Camera Raw Image Denoising.
Yang, Chin-Chang; Guo, Shu-Mei; Tsai, Jason Sheng-Hong
2017-09-01
An evolutionary fuzzy block-matching-based image denoising algorithm is proposed to remove noise from a camera raw image. Recently, a variance stabilization transform is widely used to stabilize the noise variance, so that a Gaussian denoising algorithm can be used to remove the signal-dependent noise in camera sensors. However, in the stabilized domain, the existed denoising algorithm may blur too much detail. To provide a better estimate of the noise-free signal, a new block-matching approach is proposed to find similar blocks by the use of a type-2 fuzzy logic system (FLS). Then, these similar blocks are averaged with the weightings which are determined by the FLS. Finally, an efficient differential evolution is used to further improve the performance of the proposed denoising algorithm. The experimental results show that the proposed denoising algorithm effectively improves the performance of image denoising. Furthermore, the average performance of the proposed method is better than those of two state-of-the-art image denoising algorithms in subjective and objective measures.
Wu, Liping; Oshima, Tadayuki; Tomita, Toshihiko; Ohda, Yoshio; Fukui, Hirokazu; Watari, Jiro; Miwa, Hiroto
2016-11-01
Serotonin regulates gastrointestinal function, and mast cells are a potential nonneuronal source of serotonin in the esophagus. Tight junction (TJ) proteins in the esophageal epithelium contribute to the barrier function, and the serotonin signaling pathway may contribute to epithelial leakage in gastroesophageal reflux disease. Therefore, the aim of this study was to investigate the role of serotonin on barrier function, TJ proteins, and related signaling pathways. Normal primary human esophageal epithelial cells were cultured with use of an air-liquid interface system. Serotonin was added to the basolateral compartment, and transepithelial electrical resistance (TEER) was measured. The expression of TJ proteins and serotonin receptor 7 (5-HT 7 ) was assessed by Western blotting. The involvement of 5-HT 7 was assessed with use of an antagonist and an agonist. The underlying cellular signaling pathways were examined with use of specific blockers. Serotonin decreased TEER and reduced the expression of TJ proteins ZO-1, occludin, and claudin 1, but not claudin 4. A 5-HT 7 antagonist blocked the serotonin-induced decrease in TEER, and a 5-HT 7 agonist decreased TEER. Inhibition of p38 mitogen-activated protein kinase (MAPK) reduced the serotonin-induced decrease in TEER. Inhibition of p38 MAPK blocked the decrease of ZO-1 levels, whereas extracellular-signal-regulated kinase (ERK) inhibition blocked the decrease in occludin levels. Cell signaling pathway inhibitors had no effect on serotonin-induced alterations in claudin 1 and claudin 4 levels. Serotonin induced phosphorylation of p38 MAPK and ERK, and a 5-HT 7 antagonist partially blocked serotonin-induced phosphorylation of p38 MAPK but not that of ERK. Serotonin disrupted esophageal squamous epithelial barrier function by modulating the levels of TJ proteins. Serotonin signaling pathways may mediate the pathogenesis of gastroesophageal reflux disease.
Mynott, Tracey L.; Crossett, Ben; Prathalingam, S. Radhika
2002-01-01
Bromelain, a mixture of cysteine proteases from pineapple stems, blocks signaling by the mitogen-activated protein (MAP) kinases extracellular regulated kinase 1 (ERK-1) and ERK-2, inhibits inflammation, and protects against enterotoxigenic Escherichia coli infection. In this study, we examined the effect of bromelain on Salmonella enterica serovar Typhimurium infection, since an important feature of its pathogenesis is its ability to induce activation of ERK-1 and ERK-2, which leads to internalization of bacteria and induction of inflammatory responses. Our results show that bromelain dose dependently blocks serovar Typhimurium-induced ERK-1, ERK-2, and c-Jun NH2-terminal kinase (JNK) activation in Caco-2 cells. Bromelain also blocked signaling induced by carbachol and anisomycin, pharmacological MAP kinase agonists. Despite bromelain inhibition of serovar Typhimurium-induced MAP kinase signaling, it did not prevent subsequent invasion of the Caco-2 cells by serovar Typhimurium or alter serovar Typhimurium -induced decreases in resistance across Caco-2 monolayers. Surprisingly, bromelain also did not block serovar Typhimurium-induced interleukin-8 (IL-8) secretion but synergized with serovar Typhimurium to enhance IL-8 production. We also found that serovar Typhimurium does not induce ERK phosphorylation in Caco-2 cells in the absence of serum but that serovar Typhimurium-induced invasion and decreases in monolayer resistance are unaffected. Collectively, these data indicate that serovar Typhimurium-induced invasion of Caco-2 cells, changes in the resistance of epithelial cell monolayers, and IL-8 production can occur independently of the ERK and JNK signaling pathways. Data also confirm that bromelain is a novel inhibitor of MAP kinase signaling pathways and suggest a novel role for proteases as inhibitors of signal transduction pathways in intestinal epithelial cells. PMID:11748167
Modulation format identification aided hitless flexible coherent transceiver.
Xiang, Meng; Zhuge, Qunbi; Qiu, Meng; Zhou, Xingyu; Zhang, Fangyuan; Tang, Ming; Liu, Deming; Fu, Songnian; Plant, David V
2016-07-11
We propose a hitless flexible coherent transceiver enabled by a novel modulation format identification (MFI) scheme for dynamic agile optical networks. The modulation format transparent digital signal processing (DSP) is realized by a block-wise decision-directed least-mean-square (DD-LMS) equalizer for channel tracking, and a pilot symbol aided superscalar phase locked loop (PLL) for carrier phase estimation (CPE). For the MFI, the modulation format information is encoded onto the pilot symbols initially used for CPE. Therefore, the proposed MFI method does not require extra overhead. Moreover, it can identify arbitrary modulation formats including multi-dimensional formats, and it enables tracking of the format change for short data blocks. The performance of the proposed hitless flexible coherent transceiver is successfully evaluated with five modulation formats including QPSK, 16QAM, 64QAM, Hybrid QPSK/8QAM and set-partitioning (SP)-512-QAM. We show that the proposed MFI method induces a negligible performance penalty. Moreover, we experimentally demonstrate that such a hitless transceiver can adapt to fast block-by-block modulation format switching. Finally, the performance improvement of the proposed MFI method is experimentally verified with respect to other commonly used MFI methods.
Initiation and patterning of the snake dentition are dependent on Sonic hedgehog signaling.
Buchtová, Marcela; Handrigan, Gregory R; Tucker, Abigail S; Lozanoff, Scott; Town, Liam; Fu, Katherine; Diewert, Virginia M; Wicking, Carol; Richman, Joy M
2008-07-01
Here we take the first look at cellular dynamics and molecular signaling in the developing snake dentition. We found that tooth formation differs from rodents in several respects. The majority of snake teeth bud off of a deep, ribbon-like dental lamina rather than as separate tooth germs. Prior to and after dental lamina ingrowth, we observe asymmetries in cell proliferation and extracellular matrix distribution suggesting that localized signaling by a secreted protein is involved. We cloned Sonic hedgehog from the African rock python Python sebae and traced its expression in the species as well as in two other snakes, the closely-related Python regius and the more derived corn snake Elaphe guttata (Colubridae). We found that expression of Shh is first confined to the odontogenic band and defines the position of the future dental lamina. Shh transcripts in pythons are progressively restricted to the oral epithelium on one side of the dental lamina and remain in this position throughout the prehatching period. Shh is expressed in the inner enamel epithelium and the stellate reticulum of the tooth anlagen, but is absent from the outer enamel epithelium and its derivative, the successional lamina. This suggests that signals other than Shh are responsible for replacement tooth formation. Functional studies using cyclopamine to block Hh signaling during odontogenesis prevented initiation and extension of the dental lamina into the mesenchyme, and also affected the directionality of this process. Further, blocking Hh signaling led to disruptions of the inner enamel epithelium. To explore the role of Shh in lamina extension, we looked at its expression in the premaxillary teeth, which form closer to the oral surface than elsewhere in the mouth. Oral ectodermal Shh expression in premaxillary teeth is lost soon after the teeth form reinforcing the idea that Shh is controlling the depth of the dental lamina. In summary, we have found diverse roles for Shh in patterning the snake dentition but, have excluded the participation of this signal in replacement tooth formation.
OptoRadio: a method of wireless communication using orthogonal M-ary PSK (OMPSK) modulation
NASA Astrophysics Data System (ADS)
Gaire, Sunil Kumar; Faruque, Saleh; Ahamed, Md. Maruf
2016-09-01
Laser based radio communication system, i.e. OptoRadio, using Orthogonal M-ary PSK Modulation scheme is presented in this paper. In this scheme, when a block of data needs to be transmitted, the corresponding block of biorthogonal code is transmitted by means of multi-phase shift keying. At the receiver, two photo diodes are cross coupled. The effect is that the net output power due to ambient light is close to zero. The laser signal is then transmitted only into one of the receivers. With all other signals being cancelled out, the laser signal is an overwhelmingly dominant signal. The detailed design, bit error correction capabilities, and bandwidth efficiency are presented to illustrate the concept.
Attentional influences on functional mapping of speech sounds in human auditory cortex
Obleser, Jonas; Elbert, Thomas; Eulitz, Carsten
2004-01-01
Background The speech signal contains both information about phonological features such as place of articulation and non-phonological features such as speaker identity. These are different aspects of the 'what'-processing stream (speaker vs. speech content), and here we show that they can be further segregated as they may occur in parallel but within different neural substrates. Subjects listened to two different vowels, each spoken by two different speakers. During one block, they were asked to identify a given vowel irrespectively of the speaker (phonological categorization), while during the other block the speaker had to be identified irrespectively of the vowel (speaker categorization). Auditory evoked fields were recorded using 148-channel magnetoencephalography (MEG), and magnetic source imaging was obtained for 17 subjects. Results During phonological categorization, a vowel-dependent difference of N100m source location perpendicular to the main tonotopic gradient replicated previous findings. In speaker categorization, the relative mapping of vowels remained unchanged but sources were shifted towards more posterior and more superior locations. Conclusions These results imply that the N100m reflects the extraction of abstract invariants from the speech signal. This part of the processing is accomplished in auditory areas anterior to AI, which are part of the auditory 'what' system. This network seems to include spatially separable modules for identifying the phonological information and for associating it with a particular speaker that are activated in synchrony but within different regions, suggesting that the 'what' processing can be more adequately modeled by a stream of parallel stages. The relative activation of the parallel processing stages can be modulated by attentional or task demands. PMID:15268765
Coate, Thomas M.; Swanson, Tracy L.; Copenhaver, Philip F.
2011-01-01
Reverse signaling via GPI-linked Ephrins may help control cell proliferation and outgrowth within the nervous system, but the mechanisms underlying this process remain poorly understood. In the embryonic enteric nervous system (ENS) of the moth Manduca sexta, migratory neurons forming the enteric plexus (EP cells) express a single Ephrin ligand (GPI-linked MsEphrin), while adjacent midline cells that are inhibitory to migration express the cognate receptor (MsEph). Knocking down MsEph receptor expression in cultured embryos with antisense morpholino oligonucleotides allowed the EP cells to cross the midline inappropriately, consistent with the model that reverse signaling via MsEphrin mediates a repulsive response in the ENS. Src family kinases have been implicated in reverse signaling by type-A Ephrins in other contexts, and MsEphrin colocalizes with activated forms of endogenous Src in the leading processes of the EP cells. Pharmacological inhibition of Src within the developing ENS induced aberrant midline crossovers, similar to the effect of blocking MsEphrin reverse signaling. Hyperstimulating MsEphrin reverse signaling with MsEph-Fc fusion proteins induced the rapid activation of endogenous Src specifically within the EP cells, as assayed by Western blots of single embryonic gut explants and by whole-mount immunostaining of cultured embryos. In longer cultures, treatment with MsEph-Fc caused a global inhibition of EP cell migration and outgrowth, an effect that was prevented by inhibiting Src activation. These results support the model that MsEphrin reverse signaling induces the Src-dependent retraction of EP cell processes away from the enteric midline, thereby helping to confine the neurons to their appropriate pathways. PMID:19295147
Okuyama, H; Shimahara, Y; Kawada, N; Seki, S; Kristensen, D B; Yoshizato, K; Uyama, N; Yamaoka, Y
2001-07-27
Redox-regulated processes are important elements in various cellular functions. Reducing agents, such as N-acetyl-l-cysteine (NAC), are known to regulate signal transduction and cell growth through their radical scavenging action. However, recent studies have shown that reactive oxygen species are not always involved in ligand-stimulated intracellular signaling. Here, we report a novel mechanism by which NAC blocks platelet-derived growth factor (PDGF)-induced signaling pathways in hepatic stellate cells, a fibrogenic player in the liver. Unlike in vascular smooth muscle cells, we found that reducing agents, including NAC, triggered extracellular proteolysis of PDGF receptor-beta, leading to desensitization of hepatic stellate cells toward PDGF-BB. This effect was mediated by secreted mature cathepsin B. In addition, type II transforming growth factor-beta receptor was also down-regulated. Furthermore, these events seemed to cause a dramatic improvement of rat liver fibrosis. These results indicated that redox processes impact the cell's response to growth factors by regulating the turnover of growth factor receptors and that "redox therapy" is promising for fibrosis-related disease.
Chung, King
2004-01-01
This review discusses the challenges in hearing aid design and fitting and the recent developments in advanced signal processing technologies to meet these challenges. The first part of the review discusses the basic concepts and the building blocks of digital signal processing algorithms, namely, the signal detection and analysis unit, the decision rules, and the time constants involved in the execution of the decision. In addition, mechanisms and the differences in the implementation of various strategies used to reduce the negative effects of noise are discussed. These technologies include the microphone technologies that take advantage of the spatial differences between speech and noise and the noise reduction algorithms that take advantage of the spectral difference and temporal separation between speech and noise. The specific technologies discussed in this paper include first-order directional microphones, adaptive directional microphones, second-order directional microphones, microphone matching algorithms, array microphones, multichannel adaptive noise reduction algorithms, and synchrony detection noise reduction algorithms. Verification data for these technologies, if available, are also summarized. PMID:15678225
An, Yanru; Xue, Guosheng; Shaobo, Yang; Mingxi, Deng; Zhou, Xiaowei; Yu, Weichuan; Ishibashi, Toyotaka; Zhang, Lei; Yan, Yan
2017-06-15
Cell delamination is a conserved morphogenetic process important for the generation of cell diversity and maintenance of tissue homeostasis. Here, we used Drosophila embryonic neuroblasts as a model to study the apical constriction process during cell delamination. We observe dynamic myosin signals both around the cell adherens junctions and underneath the cell apical surface in the neuroectoderm. On the cell apical cortex, the nonjunctional myosin forms flows and pulses, which are termed medial myosin pulses. Quantitative differences in medial myosin pulse intensity and frequency are crucial to distinguish delaminating neuroblasts from their neighbors. Inhibition of medial myosin pulses blocks delamination. The fate of a neuroblast is set apart from that of its neighbors by Notch signaling-mediated lateral inhibition. When we inhibit Notch signaling activity in the embryo, we observe that small clusters of cells undergo apical constriction and display an abnormal apical myosin pattern. Together, these results demonstrate that a contractile actomyosin network across the apical cell surface is organized to drive apical constriction in delaminating neuroblasts. © 2017. Published by The Company of Biologists Ltd.
Peiffer, Isabelle; Servin, Alain L.; Bernet-Camard, Marie-Françoise
1998-01-01
Diffusely adhering Escherichia coli (DAEC) C1845 (clinical isolate) harboring the fimbrial adhesin F1845 can infect cultured human differentiated intestinal epithelial cells; this process is followed by the disassembly of the actin network in the apical domain. The aim of this study was to examine the mechanism by which DAEC C1845 promotes F-actin rearrangements. For this purpose, we used a human embryonic intestinal cell line (INT407) expressing the membrane-associated glycosylphosphatidylinositol (GPI) protein-anchored decay-accelerating factor (DAF), the receptor of the F1845 adhesin. We show here that infection of INT407 cells by DAEC C1845 can provoke dramatic F-actin rearrangements without cell entry. Clustering of phosphotyrosines was observed, revealing that the DAEC C1845-DAF interaction involves the recruitment of signal transduction molecules. A pharmacological approach with a subset of inhibitors of signal transduction molecules was used to identify the cascade of signal transduction molecules that are coupled to the DAF, that are activated upon infection, and that promote the F-actin rearrangements. DAEC C1845-induced F-actin rearrangements can be blocked dose dependently by protein tyrosine kinase, phospholipase Cγ, phosphatidylinositol 3-kinase, protein kinase C, and Ca2+ inhibitors. F-actin rearrangements and blocking by inhibitors were observed after infection of the cells with two E. coli recombinants carrying the plasmids containing the fimbrial adhesin F1845 or the fimbrial hemagglutinin Dr, belonging to the same family of adhesins. These findings show that the DAEC Dr family of pathogens promotes alterations in the intestinal cell cytoskeleton by piracy of the DAF-GPI signal cascade without bacterial cell entry. PMID:9712744
Code of Federal Regulations, 2011 CFR
2011-10-01
... TRANSPORTATION SIGNAL SYSTEMS REPORTING REQUIREMENTS § 233.1 Scope. This part prescribed reporting requirements with respect to methods of train operation, block signal systems, interlockings, traffic control systems, automatic train stop, train control, and cab signal systems, or other similar appliances, methods...
Code of Federal Regulations, 2010 CFR
2010-10-01
... TRANSPORTATION SIGNAL SYSTEMS REPORTING REQUIREMENTS § 233.1 Scope. This part prescribed reporting requirements with respect to methods of train operation, block signal systems, interlockings, traffic control systems, automatic train stop, train control, and cab signal systems, or other similar appliances, methods...
Behavioral Signal Processing: Deriving Human Behavioral Informatics From Speech and Language
Narayanan, Shrikanth; Georgiou, Panayiotis G.
2013-01-01
The expression and experience of human behavior are complex and multimodal and characterized by individual and contextual heterogeneity and variability. Speech and spoken language communication cues offer an important means for measuring and modeling human behavior. Observational research and practice across a variety of domains from commerce to healthcare rely on speech- and language-based informatics for crucial assessment and diagnostic information and for planning and tracking response to an intervention. In this paper, we describe some of the opportunities as well as emerging methodologies and applications of human behavioral signal processing (BSP) technology and algorithms for quantitatively understanding and modeling typical, atypical, and distressed human behavior with a specific focus on speech- and language-based communicative, affective, and social behavior. We describe the three important BSP components of acquiring behavioral data in an ecologically valid manner across laboratory to real-world settings, extracting and analyzing behavioral cues from measured data, and developing models offering predictive and decision-making support. We highlight both the foundational speech and language processing building blocks as well as the novel processing and modeling opportunities. Using examples drawn from specific real-world applications ranging from literacy assessment and autism diagnostics to psychotherapy for addiction and marital well being, we illustrate behavioral informatics applications of these signal processing techniques that contribute to quantifying higher level, often subjectively described, human behavior in a domain-sensitive fashion. PMID:24039277
Development of low optical cross talk filters for VIIRS (JPSS)
NASA Astrophysics Data System (ADS)
Murgai, Vijay; Hendry, Derek; Downing, Kevin; Carbone, David; Potter, John
2016-09-01
The Visible/Infrared Imaging Radiometer Suite (VIIRS) is a key sensor on Suomi National Polar-orbiting Partnership (S-NPP) satellite launched on October 28, 2011 into a polar orbit of 824 km nominal altitude and the JPSS sensors currently being built and integrated. VIIRS collects radiometric and imagery data of the Earth's atmosphere, oceans, and land surfaces in 22 spectral bands spanning the visible and infrared spectrum from 0.4 to 12.5 μm. Interference filters assembled in `butcher-block' arrays mounted adjacent to focal plane arrays provide spectral definition. Out-of-band signal and out-of-band optical cross-talk was observed for bands in the 0.4 to 1 μm range in testing of VIIRS for S-NPP. Optical cross-talk is in-band or out-of-band light incident on an adjacent filter or adjacent region of the same filter reaching the detector. Out-of-band optical cross-talk results in spectral and spatial `impurities' in the signal and consequent errors in the calculated environmental parameters such as ocean color that rely on combinations of signals from more than one band. This paper presents results of characterization, specification, and coating process improvements that enabled production of filters with significantly reduced out of band light for Joint Polar Satellite System (JPSS) J1 and subsequent sensors. Total transmission and scatter measurements at a wavelength within the pass band can successfully characterize filter performance prior to dicing and assembling filters into butcher block assemblies. Coating and process development demonstrated performance on test samples followed by production of filters for J1 and J2. Results for J1 and J2 filters are presented.
Model for the role of auxin polar transport in patterning of the leaf adaxial-abaxial axis.
Shi, Jianmin; Dong, Jiaqiang; Xue, Jingshi; Wang, Hua; Yang, Zhongnan; Jiao, Yuling; Xu, Lin; Huang, Hai
2017-11-01
Leaf adaxial-abaxial polarity refers to the two leaf faces, which have different types of cells performing distinct biological functions. In 1951, Ian Sussex reported that when an incipient leaf primordium was surgically isolated by an incision across the vegetative shoot apical meristem (SAM), a radialized structure without an adaxial domain would form. This led to the proposal that a signal, now called the Sussex signal, is transported from the SAM to emerging primordia to direct leaf adaxial-abaxial patterning. It was recently proposed that instead of the Sussex signal, polar transport of the plant hormone auxin is critical in leaf polarity formation. However, how auxin polar transport functions in the process is unknown. Through live imaging, we established a profile of auxin polar transport in and around young leaf primordia. Here we show that auxin polar transport in lateral regions of an incipient primordium forms auxin convergence points. We demonstrated that blocking auxin polar transport in the lateral regions of the incipient primordium by incisions abolished the auxin convergence points and caused abaxialized leaves to form. The lateral incisions also blocked the formation of leaf middle domain and margins and disrupted expression of the middle domain/margin-associated marker gene WUSCHEL-RELATED HOMEOBOX 1 (SlWOX1). Based on these results we propose that the auxin convergence points are required for the formation of leaf middle domain and margins, and the functional middle domain and margins ensure leaf adaxial-abaxial polarity. How middle domain and margins function in the process is discussed. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.
Design of an Intelligent Front-End Signal Conditioning Circuit for IR Sensors
NASA Astrophysics Data System (ADS)
de Arcas, G.; Ruiz, M.; Lopez, J. M.; Gutierrez, R.; Villamayor, V.; Gomez, L.; Montojo, Mª. T.
2008-02-01
This paper presents the design of an intelligent front-end signal conditioning system for IR sensors. The system has been developed as an interface between a PbSe IR sensor matrix and a TMS320C67x digital signal processor. The system architecture ensures its scalability so it can be used for sensors with different matrix sizes. It includes an integrator based signal conditioning circuit, a data acquisition converter block, and a FPGA based advanced control block that permits including high level image preprocessing routines such as faulty pixel detection and sensor calibration in the signal conditioning front-end. During the design phase virtual instrumentation technologies proved to be a very valuable tool for prototyping when choosing the best A/D converter type for the application. Development time was significantly reduced due to the use of this technology.
Assessment of the Dominant Path Model and Field Measurements for NLOS DTV Signal Propagation
NASA Astrophysics Data System (ADS)
Adonias, Geoflly L.; Carvalho, Joabson N.
2018-03-01
In Brazil, one of the most important telecommunications systems is broadcast television. Such relevance demands an extensive analysis to be performed chasing technical excellence in order to offer a better digital transmission to the user. Therefore, it is mandatory to evaluate the quality and strength of the Digital TV signal, through studies of coverage predictions models, allowing stations to be projected in a way that their respective signals are harmoniously distributed. The purpose of this study is to appraise measurements of digital television signal obtained in the field and to compare them with numerical results from the simulation of the Dominant Path Model. The outcomes indicate possible blocking zones and a low accumulated probability index above the reception threshold, as well as characterise the gain level of the receiving antenna, which would prevent signal blocking.
Multifocus watermarking approach based on discrete cosine transform.
Waheed, Safa Riyadh; Alkawaz, Mohammed Hazim; Rehman, Amjad; Almazyad, Abdulaziz S; Saba, Tanzila
2016-05-01
Image fusion process consolidates data and information from various images of same sight into a solitary image. Each of the source images might speak to a fractional perspective of the scene, and contains both "pertinent" and "immaterial" information. In this study, a new image fusion method is proposed utilizing the Discrete Cosine Transform (DCT) to join the source image into a solitary minimized image containing more exact depiction of the sight than any of the individual source images. In addition, the fused image comes out with most ideal quality image without bending appearance or loss of data. DCT algorithm is considered efficient in image fusion. The proposed scheme is performed in five steps: (1) RGB colour image (input image) is split into three channels R, G, and B for source images. (2) DCT algorithm is applied to each channel (R, G, and B). (3) The variance values are computed for the corresponding 8 × 8 blocks of each channel. (4) Each block of R of source images is compared with each other based on the variance value and then the block with maximum variance value is selected to be the block in the new image. This process is repeated for all channels of source images. (5) Inverse discrete cosine transform is applied on each fused channel to convert coefficient values to pixel values, and then combined all the channels to generate the fused image. The proposed technique can potentially solve the problem of unwanted side effects such as blurring or blocking artifacts by reducing the quality of the subsequent image in image fusion process. The proposed approach is evaluated using three measurement units: the average of Q(abf), standard deviation, and peak Signal Noise Rate. The experimental results of this proposed technique have shown good results as compared with older techniques. © 2016 Wiley Periodicals, Inc.
49 CFR 235.5 - Changes requiring filing of application.
Code of Federal Regulations, 2010 CFR
2010-10-01
... system, automatic train stop, train control, or cab signal system or other similar appliance or device..., automatic train stop, train control, or cab signal system; or (3) The modification of a block signal system, interlocking, traffic control system, automatic train stop, train control, or cab signal system. (b) [Reserved...
49 CFR 235.5 - Changes requiring filing of application.
Code of Federal Regulations, 2011 CFR
2011-10-01
... system, automatic train stop, train control, or cab signal system or other similar appliance or device..., automatic train stop, train control, or cab signal system; or (3) The modification of a block signal system, interlocking, traffic control system, automatic train stop, train control, or cab signal system. (b) [Reserved...
Inta, Ra; Lai, Joseph C S; Fu, Eugene W; Evans, Theodore A
2007-08-22
Drywood termites are able to assess wood size using vibratory signals, although the exact mechanism behind this assessment ability is not known. Important vibratory characteristics such as the modal frequencies of a wooden block depend on its geometry and boundary conditions; however, they are also dependent on the material characteristics of the block, such as mass, density and internal damping. We report here on choice experiments that tested the ability of the drywood termite Cryptotermes secundus to assess wooden block size using a solid wooden block paired with a composite block, the latter made of either wood and aluminium or wood and rubber. Each composite block was constructed to match mass or low-frequency vibratory modes (i.e. fundamental frequency) of the solid wooden block. The termites always chose the blocks with more wood; they moved to the solid wooden blocks usually within a day and then tunnelled further into the solid wooden block by the end of the experiment. Termites offered composite blocks of wood and rubber matched for mass were the slowest to show a preference for the solid wooden block and this preference was the least definitive of any treatment, which indicated that mass and/or damping may play a role in food assessment. This result clearly shows that the termites were not fooled by composite blocks matched for mass or frequency, which implies that they probably employ more than a single simple measure in their food assessment strategy. This implies a degree of sophistication in their ability to assess their environment hitherto unknown. The potential importance of alternative features in the vibrational signals is discussed.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-05-25
... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... discontinuance or modification of a signal system. FRA assigned the petition Docket Number FRA-2012-0046... discontinuance of an automatic block signal (ABS) system and a traffic control signal (TCS) system on the...
Notch Promotes Dynamin-Dependent Endocytosis of Nephrin
Waters, Aoife M.; Wu, Megan Yi Jun; Huang, Yi-Wei; Liu, Guang Ying; Holmyard, Doug; Onay, Tuncer; Jones, Nina; Egan, Sean E.; Robinson, Lisa A.
2012-01-01
Notch signaling in podocytes causes proteinuria and glomerulosclerosis in humans and rodents, but the underlying mechanism remains unknown. Here, we analyzed morphologic, molecular, and cellular events before the onset of proteinuria in newborn transgenic mice that express activated Notch in podocytes. Immunohistochemistry revealed a loss of the slit diaphragm protein nephrin exclusively in podocytes expressing activated Notch. Podocyte-specific deletion of Rbpj, which is essential for canonical Notch signaling, prevented this loss of nephrin. Overexpression of activated Notch decreased cell surface nephrin and increased cytoplasmic nephrin in transfected HEK293T cells; pharmacologic inhibition of dynamin, but not depletion of cholesterol, blocked these effects on nephrin, suggesting that Notch promotes dynamin-dependent, raft-independent endocytosis of nephrin. Supporting an association between Notch signaling and nephrin trafficking, electron microscopy revealed shortened podocyte foot processes and fewer slit diaphragms among the transgenic mice compared with controls. These data suggest that Notch signaling induces endocytosis of nephrin, thereby triggering the onset of proteinuria. PMID:22052054
DAG tales: the multiple faces of diacylglycerol--stereochemistry, metabolism, and signaling.
Eichmann, Thomas Oliver; Lass, Achim
2015-10-01
The neutral lipids diacylglycerols (DAGs) are involved in a plethora of metabolic pathways. They function as components of cellular membranes, as building blocks for glycero(phospho)lipids, and as lipid second messengers. Considering their central role in multiple metabolic processes and signaling pathways, cellular DAG levels require a tight regulation to ensure a constant and controlled availability. Interestingly, DAG species are versatile in their chemical structure. Besides the different fatty acid species esterified to the glycerol backbone, DAGs can occur in three different stereo/regioisoforms, each with unique biological properties. Recent scientific advances have revealed that DAG metabolizing enzymes generate and distinguish different DAG isoforms, and that only one DAG isoform holds signaling properties. Herein, we review the current knowledge of DAG stereochemistry and their impact on cellular metabolism and signaling. Further, we describe intracellular DAG turnover and its stereochemistry in a 3-pool model to illustrate the spatial and stereochemical separation and hereby the diversity of cellular DAG metabolism.
Novel active signal compression in low-noise analog readout at future X-ray FEL facilities
NASA Astrophysics Data System (ADS)
Manghisoni, M.; Comotti, D.; Gaioni, L.; Lodola, L.; Ratti, L.; Re, V.; Traversi, G.; Vacchi, C.
2015-04-01
This work presents the design of a low-noise front-end implementing a novel active signal compression technique. This feature can be exploited in the design of analog readout channels for application to the next generation free electron laser (FEL) experiments. The readout architecture includes the low-noise charge sensitive amplifier (CSA) with dynamic signal compression, a time variant shaper used to process the signal at the preamplifier output and a 10-bit successive approximation register (SAR) analog-to-digital converter (ADC). The channel will be operated in such a way to cope with the high frame rate (exceeding 1 MHz) foreseen for future XFEL machines. The choice of a 65 nm CMOS technology has been made in order to include all the building blocks in the target pixel pitch of 100 μm. This work has been carried out in the frame of the PixFEL Project funded by the Istituto Nazionale di Fisica Nucleare (INFN), Italy.
Evaluation of non-selective refocusing pulses for 7 T MRI
Moore, Jay; Jankiewicz, Marcin; Anderson, Adam W.; Gore, John C.
2011-01-01
There is a continuing need for improved RF pulses that achieve proper refocusing in the context of ultra-high field (≥ 7 T) human MRI. Simple block or sinc pulses are highly susceptible to RF field inhomogeneities, and adiabatic pulses are generally considered too SAR intensive for practical use at 7 T. The performance of the array of pulses falling between these extremes, however, has not been systematically evaluated. The aim of this work was to compare the performances of 21 non-selective refocusing pulses spanning a range of durations and SAR levels. The evaluation was based upon simulations and both phantom and in vivo human brain experiments conducted at 7 T. Tested refocusing designs included block, composite block, BIR-4, hyperbolic secant, and numerically optimized composite waveforms. These pulses were divided into three SAR classes and two duration categories, and, based on signal gain in a 3-D spin echo sequence, practical recommendations on usage are made within each category. All evaluated pulses were found to produce greater volume-averaged signals relative to a 180° block pulse. Although signal gains often come with the price of increased SAR or duration, some pulses were found to result in significant signal enhancement while also adhering to practical constraints. This work demonstrates the signal gains and losses realizable with single-channel refocusing pulse designs and should assist in the selection of suitable refocusing pulses for practical 3-D spin-echo imaging at 7 T. It further establishes a reference against which future pulses and multi-channel designs can be compared. PMID:22177384
2013-06-01
Radio is a software development toolkit that provides signal processing blocks to drive the SDR. GNU Radio has many strong points – it is actively...maintained with a large user base, new capabilities are constantly being added, and compiled C code is fast for many real-time applications such as...programming interface (API) makes learning the architecture a daunting task, even for the experienced software developer. This requirement poses many
Heme-induced Trypanosoma cruzi proliferation is mediated by CaM kinase II
DOE Office of Scientific and Technical Information (OSTI.GOV)
Souza, C.F.; Carneiro, A.B.; Silveira, A.B.
2009-12-18
Trypanosoma cruzi, the etiologic agent of Chagas disease, is transmitted through triatomine vectors during their blood-meal on vertebrate hosts. These hematophagous insects usually ingest approximately 10 mM of heme bound to hemoglobin in a single meal. Blood forms of the parasite are transformed into epimastigotes in the crop which initiates a few hours after parasite ingestion. In a previous work, we investigated the role of heme in parasite cell proliferation and showed that the addition of heme significantly increased parasite proliferation in a dose-dependent manner . To investigate whether the heme effect is mediated by protein kinase signalling pathways, parasitemore » proliferation was evaluated in the presence of several protein kinase (PK) inhibitors. We found that only KN-93, a classical inhibitor of calcium-calmodulin-dependent kinases (CaMKs), blocked heme-induced cell proliferation. KN-92, an inactive analogue of KN-93, was not able to block this effect. A T. cruzi CaMKII homologue is most likely the main enzyme involved in this process since parasite proliferation was also blocked when Myr-AIP, an inhibitory peptide for mammalian CaMKII, was included in the cell proliferation assay. Moreover, CaMK activity increased in parasite cells with the addition of heme as shown by immunological and biochemical assays. In conclusion, the present results are the first strong indications that CaMKII is involved in the heme-induced cell signalling pathway that mediates parasite proliferation.« less
Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs.
Cheng, Liang; Ma, Jianping; Li, Jingyun; Li, Dan; Li, Guangming; Li, Feng; Zhang, Qing; Yu, Haisheng; Yasui, Fumihiko; Ye, Chaobaihui; Tsao, Li-Chung; Hu, Zhiyuan; Su, Lishan; Zhang, Liguo
2017-01-03
Despite the efficient suppression of HIV-1 replication that can be achieved with combined antiretroviral therapy (cART), low levels of type I interferon (IFN-I) signaling persist in some individuals. This sustained signaling may impede immune recovery and foster viral persistence. Here we report studies using a monoclonal antibody to block IFN-α/β receptor (IFNAR) signaling in humanized mice (hu-mice) that were persistently infected with HIV-1. We discovered that effective cART restored the number of human immune cells in HIV-1-infected hu-mice but did not rescue their immune hyperactivation and dysfunction. IFNAR blockade fully reversed HIV-1-induced immune hyperactivation and rescued anti-HIV-1 immune responses in T cells from HIV-1-infected hu-mice. Finally, we found that IFNAR blockade in the presence of cART reduced the size of HIV-1 reservoirs in lymphoid tissues and delayed HIV-1 rebound after cART cessation in the HIV-1-infected hu-mice. We conclude that low levels of IFN-I signaling contribute to HIV-1-associated immune dysfunction and foster HIV-1 persistence in cART-treated hosts. Our results suggest that blocking IFNAR may provide a potential strategy to enhance immune recovery and reduce HIV-1 reservoirs in individuals with sustained elevations in IFN-I signaling during suppressive cART.
Possible mechanisms for four regimes associated with cold events over East Asia
NASA Astrophysics Data System (ADS)
Yang, Zifan; Huang, Wenyu; Wang, Bin; Chen, Ruyan; Wright, Jonathon S.; Ma, Wenqian
2017-09-01
Circulation patterns associated with cold events over East Asia during the winter months of 1948-2014 are classified into four regimes by applying a k-means clustering method based on the area-weighted pattern correlation. The earliest precursor signals for two regimes are anticyclonic anomalies, which evolve into Ural and central Siberian blocking-like circulation patterns. The earliest precursor signals for the other two regimes are cyclonic anomalies, both of which evolve to amplify the East Asian trough (EAT). Both the blocking-like circulation patterns and amplified EAT favor the initialization of cold events. On average, the blocking-related regimes tend to last longer. The lead time of the earliest precursor signal for the central Siberian blocking-related regime is only 4 days, while those for the other regimes range from 16 to 18 days. The North Atlantic Oscillation plays essential roles both in triggering the precursor for the Ural blocking-related regime and in amplifying the precursors for all regimes. All regimes preferentially occur during the positive phase of the Eurasian teleconnection pattern and the negative phase of the El Niño-Southern Oscillation. For three regimes, surface cooling is primarily due to reduced downward infrared radiation and enhanced cold advection. For the remaining regime, which is associated with the southernmost cooling center, sensible and latent heat release and horizontal cold advection dominate the East Asian cooling.
NASA Astrophysics Data System (ADS)
Bisson, Melanie M. A.; Kessenbrock, Mareike; Müller, Lena; Hofmann, Alexander; Schmitz, Florian; Cristescu, Simona M.; Groth, Georg
2016-08-01
The plant hormone ethylene is involved in the regulation of several processes with high importance for agricultural applications, e.g. ripening, aging and senescence. Previous work in our group has identified a small peptide (NOP-1) derived from the nuclear localization signal of the Arabidopsis ethylene regulator ETHYLENE INSENSITIVE-2 (EIN2) C-terminal part as efficient inhibitor of ethylene responses. Here, we show that NOP-1 is also able to efficiently disrupt EIN2-ETR1 complex formation in tomato, indicating that the NOP-1 inhibition mode is conserved across plant species. Surface application of NOP-1 on green tomato fruits delays ripening similar to known inhibitors of ethylene perception (MCP) and ethylene biosynthesis (AVG). Fruits treated with NOP-1 showed similar ethylene production as untreated controls underlining that NOP-1 blocks ethylene signaling by targeting an essential interaction in this pathway, while having no effect on ethylene biosynthesis.
Exploitation of Ubiquitous Wi-Fi Devices as Building Blocks for Improvised Motion Detection Systems.
Soldovieri, Francesco; Gennarelli, Gianluca
2016-02-27
This article deals with a feasibility study on the detection of human movements in indoor scenarios based on radio signal strength variations. The sensing principle exploits the fact that the human body interacts with wireless signals, introducing variations of the radiowave fields due to shadowing and multipath phenomena. As a result, human motion can be inferred from fluctuations of radiowave power collected by a receiving terminal. In this paper, we investigate the potentialities of widely available wireless communication devices in order to develop an improvised motion detection system (IMDS). Experimental tests are performed in an indoor environment by using a smartphone as a Wi-Fi access point and a laptop with dedicated software as a receiver. Simple detection strategies tailored for real-time operation are implemented to process the received signal strength measurements. The achieved results confirm the potentialities of the simple system here proposed to reliably detect human motion in operational conditions.
Bisson, Melanie M A; Kessenbrock, Mareike; Müller, Lena; Hofmann, Alexander; Schmitz, Florian; Cristescu, Simona M; Groth, Georg
2016-08-01
The plant hormone ethylene is involved in the regulation of several processes with high importance for agricultural applications, e.g. ripening, aging and senescence. Previous work in our group has identified a small peptide (NOP-1) derived from the nuclear localization signal of the Arabidopsis ethylene regulator ETHYLENE INSENSITIVE-2 (EIN2) C-terminal part as efficient inhibitor of ethylene responses. Here, we show that NOP-1 is also able to efficiently disrupt EIN2-ETR1 complex formation in tomato, indicating that the NOP-1 inhibition mode is conserved across plant species. Surface application of NOP-1 on green tomato fruits delays ripening similar to known inhibitors of ethylene perception (MCP) and ethylene biosynthesis (AVG). Fruits treated with NOP-1 showed similar ethylene production as untreated controls underlining that NOP-1 blocks ethylene signaling by targeting an essential interaction in this pathway, while having no effect on ethylene biosynthesis.
Kalkunte, Satyan; Brard, Laurent; Granai, Cornelius O; Swamy, Narasimha
2005-01-01
Angiogenesis is a complex process involving coordinated steps of endothelial cell activation, proliferation, migration, tube formation and capillary sprouting with participation of intracellular signaling pathways. Regulation of angiogenesis carries tremendous potential for cancer therapy. Our earlier studies showed that vitamin D-binding protein-macrophage activating factor (DBP-maf) acts as a potent anti-angiogenic factor and inhibits tumor growth in vivo. The goal of this investigation was to understand the effect of DBP-maf on human endothelial cell (HEC) and the mechanism of angiogenesis inhibition. DBP-maf inhibited human endothelial cell (HEC) proliferation by inhibiting DNA synthesis (IC(50) = 7.8 +/- 0.15 microg/ml). DBP-maf significantly induced S- and G0/G1-phase arrest in HEC in 72 h. DBP-maf potently blocked VEGF-induced migration, tube-formation of HEC in a dose dependent manner. In addition, DBP-maf inhibited growth factor-induced microvessel sprouting in rat aortic ring assay. Moreover, DBP-maf inhibited VEGF signaling by decreasing VEGF-mediated phosphorylation of VEGFR-2 and ERK1/2, a downstream target of VEGF signaling cascade. However, Akt activation was not affected. These studies collectively demonstrate that DBP-maf inhibits angiogenesis by blocking critical steps such as HEC proliferation, migration, tube formation and microvessel sprouting. DBP-maf exerts its effect by inhibiting VEGR-2 and ERK1/2 signaling cascades. Understanding the cellular and molecular mechanisms of anti-endothelial activity of DBP-maf will allow us to develop it as an angiogenesis targeting novel drug for tumor therapy.
Effect of interlukin-1beta on proliferation of gastric epithelial cells in culture.
Beales, Ian L P
2002-04-05
Helicobacter pylori is the main risk factor for the development of non-cardia gastric cancer. Increased proliferation of the gastric mucosa is a feature of H. pylori infection. Mucosal interkeukin-1beta production is increased in H. pylori infection and IL-1beta genotypes associated with increased pro-inflammatory activity are risk factors for the development of gastric cancer. The effect of IL-1beta on gastric epithelial cell proliferation has been examined in this study. AGS cells were cultured with IL-1beta. DNA synthesis was assed by [3H]thymidine incorporation and total viable cell numbers by MTT assay. IL-1beta dose dependently increased DNA synthesis and cell numbers. The enhanced proliferation was blocked by interleukin-1 receptor antagonist. Addition of neutralising antibody to GM-CSF reduced IL-1beta-stimulated proliferation by 31 +/- 4 %. GM-CSF alone significantly stimulated proliferation. Addition or neutralisation of IL-8 had no effect on basal or IL-1beta-stimulated proliferation. The tyrosine kinase inhibitor genistein completely blocked IL-1beta-stimulated proliferation and inhibition of the extracellular signal related kinase pathway with PD 98059 inhibited IL-1beta stimulated proliferation by 58 +/- 5 %. IL-1beta stimulates proliferation in gastric epithelial cells. Autocrine stimulation by GM-CSF contributes to this proliferative response. Signalling via tyrosine kinase activity is essential to the mitogenic response to IL-1beta. The extracellular signal related kinase pathway is involved in, but not essential to downstream signalling. IL-1beta may contribute to the hyperproliferation seen in H. pylori- infected gastric mucosa, and be involved in the carcinogenic process.
Jacques, Claire; Holzenberger, Martin; Mladenovic, Zvezdana; Salvat, Colette; Pecchi, Emilie; Berenbaum, Francis; Gosset, Marjolaine
2012-01-01
Visfatin (also termed pre-B-cell colony-enhancing factor (PBEF) or nicotinamide phosphoribosyltransferase (Nampt)) is a pleiotropic mediator acting on many inflammatory processes including osteoarthritis. Visfatin exhibits both an intracellular enzymatic activity (nicotinamide phosphoribosyltransferase, Nampt) leading to NAD synthesis and a cytokine function via the binding to its hypothetical receptor. We recently reported the role of visfatin in prostaglandin E2 (PGE2) synthesis in chondrocytes. Here, our aim was to characterize the signaling pathways involved in this response in exploring both the insulin receptor (IR) signaling pathway and Nampt activity. IR was expressed in human and murine chondrocytes, and visfatin triggered Akt phosphorylation in murine chondrocytes. Blocking IR expression with siRNA or activity using the hydroxy-2-naphthalenyl methyl phosphonic acid tris acetoxymethyl ester (HNMPA-(AM)3) inhibitor diminished visfatin-induced PGE2 release in chondrocytes. Moreover, visfatin-induced IGF-1R−/− chondrocytes released higher concentration of PGE2 than IGF-1R+/+ cells, a finding confirmed with an antibody that blocked IGF-1R. Using RT-PCR, we found that visfatin did not regulate IR expression and that an increased insulin release was also unlikely to be involved because insulin was unable to increase PGE2 release. Inhibition of Nampt activity using the APO866 inhibitor gradually decreased PGE2 release, whereas the addition of exogenous nicotinamide increased it. We conclude that the proinflammatory actions of visfatin in chondrocytes involve regulation of IR signaling pathways, possibly through the control of Nampt enzymatic activity. PMID:22399297
FXR blocks the growth of liver cancer cells through inhibiting mTOR-s6K pathway
DOE Office of Scientific and Technical Information (OSTI.GOV)
Huang, Xiongfei, E-mail: xiongfeihuang@hotmail.com; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian; Zeng, Yeting
The nuclear receptor Farnesoid X Receptor (FXR) is likely a tumor suppressor in liver tissue but its molecular mechanism of suppression is not well understood. In this study, the gene expression profile of human liver cancer cells was investigated by microarray. Bioinformatics analysis of these data revealed that FXR might regulate the mTOR/S6K signaling pathway. This was confirmed by altering the expression level of FXR in liver cancer cells. Overexpression of FXR prevented the growth of cells and induced cell cycle arrest, which was enhanced by the mTOR/S6K inhibitor rapamycin. FXR upregulation also intensified the inhibition of cell growth bymore » rapamycin. Downregulation of FXR produced the opposite effect. Finally, we found that ectopic expression of FXR in SK-Hep-1 xenografts inhibits tumor growth and reduces expression of the phosphorylated protein S6K. Taken together, our data provide the first evidence that FXR suppresses proliferation of human liver cancer cells via the inhibition of the mTOR/S6K signaling pathway. FXR expression can be used as a biomarker of personalized mTOR inhibitor treatment assessment for liver cancer patients. -- Highlights: •FXR inhibits the proliferation of liver cancer cells by prolonging G0/G1 phase. •Microarray results indicate that mTOR-S6k signaling is involved in cellular processes in which FXR plays an important role. •FXR blocks the growth of liver cancer cells via the inhibition of the mTOR/S6K signaling pathway in vitro and in vivo.« less
... of medications called antiarrhythmics. It works by slowing electrical signals in the heart to stabilize the heart ... if you have heart block (condition in which electrical signals are not passed normally from the upper ...
2014-05-01
function Value = Select_Element(Index,Signal) %# eml Value = Signal(Index); Code Listing 1 Code for Selector Block 12 | P a g e 4.3...code for the Simulink function shiftedSignal = fcn(signal,Shift) %# eml shiftedSignal = circshift(signal,Shift); Code Listing 2 Code for CircShift
Nicotine Induces Resistance to Chemotherapy by Modulating Mitochondrial Signaling in Lung Cancer
Zhang, Jingmei; Kamdar, Opal; Le, Wei; Rosen, Glenn D.; Upadhyay, Daya
2009-01-01
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 μM) followed by cisplatin (35 μM) plus etoposide (20 μM) 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-ρ0 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-therapeutic agents induce apoptosis via the mitochondrial death pathway. Strategies aimed at understanding nicotine-mediated signaling may facilitate the development of improved therapies in lung cancer. PMID:18676776
Nicotine induces resistance to chemotherapy by modulating mitochondrial signaling in lung cancer.
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-therapeutic agents induce apoptosis via the mitochondrial death pathway. Strategies aimed at understanding nicotine-mediated signaling may facilitate the development of improved therapies in lung cancer.
Selvaggio, Gianluca; Coelho, Pedro M B M; Salvador, Armindo
2014-10-01
Cells are occasionally exposed to high H2O2 concentrations, often preceding exposure to other electrophylic compounds. Both H2O2 and these compounds can irreversibly modify protein thiols, with deleterious consequences. Induction of enzymatic defenses against those agents is too slow to avoid significant damage. Cells may solve this conundrum by reversibly "blocking" the thiols once H2O2 concentrations begin to increase. We term this mechanism "anticipatory blocking" because it acts in anticipation of irreversible damage upon detection of early signs of stress. Here we examine the design requirements for the Peroxiredoxin/Thioredoxin/Thioredoxin-Reductase/Protein-Dithiol System (PTTRDS) to effectively integrate H2O2 signaling and anticipatory blocking of protein dithiols as disulfides, and we compared them to the designs found in cells. To that effect, we developed a minimal model of the PTTRDS, and we defined a set of quantitative performance criteria that embody the requirements for (a) efficient scavenging capacity, (b) low NADPH consumption, (c) effective signal propagation, and (d) effective anticipatory blocking. We then sought the design principles (relationships among rate constants and species concentrations) that warrant fulfillment of all these criteria. Experimental data indicates that the design of the PTTRDS in human erythrocytes fulfills these principles and thus accomplishes effective integration between anticipatory blocking, antioxidant protection and redox signaling. A more general analysis suggests that the same principles hold in a wide variety of cell types and organisms. We acknowledge grants PEst-C/SAU/LA0001/2013-2014, PEst-OE/QUI/UI0612/2013, FCOMP-01-0124-FEDER-020978 (PTDC/QUI-BIQ/119657/2010) financed by FEDER through the "Programa Operacional Factores de Competitividade, COMPETE" and by national funds through "FCT, Fundação para a Ciência e a Tecnologia". Copyright © 2014. Published by Elsevier Inc.
Scaling up digital circuit computation with DNA strand displacement cascades.
Qian, Lulu; Winfree, Erik
2011-06-03
To construct sophisticated biochemical circuits from scratch, one needs to understand how simple the building blocks can be and how robustly such circuits can scale up. Using a simple DNA reaction mechanism based on a reversible strand displacement process, we experimentally demonstrated several digital logic circuits, culminating in a four-bit square-root circuit that comprises 130 DNA strands. These multilayer circuits include thresholding and catalysis within every logical operation to perform digital signal restoration, which enables fast and reliable function in large circuits with roughly constant switching time and linear signal propagation delays. The design naturally incorporates other crucial elements for large-scale circuitry, such as general debugging tools, parallel circuit preparation, and an abstraction hierarchy supported by an automated circuit compiler.
Fortress, Ashley M.; Fan, Lu; Orr, Patrick T.; Zhao, Zaorui; Frick, Karyn M.
2013-01-01
The mammalian target of rapamycin (mTOR) signaling pathway is an important regulator of protein synthesis and is essential for various forms of hippocampal memory. Here, we asked whether the enhancement of object recognition memory consolidation produced by dorsal hippocampal infusion of 17β-estradiol (E2) is dependent on mTOR signaling in the dorsal hippocampus, and whether E2-induced mTOR signaling is dependent on dorsal hippocampal phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) activation. We first demonstrated that the enhancement of object recognition induced by E2 was blocked by dorsal hippocampal inhibition of ERK, PI3K, or mTOR activation. We then showed that an increase in dorsal hippocampal ERK phosphorylation 5 min after intracerebroventricular (ICV) E2 infusion was also blocked by dorsal hippocampal infusion of the three cell signaling inhibitors. Next, we found that ICV infusion of E2 increased phosphorylation of the downstream mTOR targets S6K (Thr-421) and 4E-BP1 in the dorsal hippocampus 5 min after infusion, and that this phosphorylation was blocked by dorsal hippocampal infusion of inhibitors of ERK, PI3K, and mTOR. Collectively, these data demonstrate for the first time that activation of the dorsal hippocampal mTOR signaling pathway is necessary for E2 to enhance object recognition memory consolidation and that E2-induced mTOR activation is dependent on upstream activation of ERK and PI3K signaling. PMID:23422279
Signal Prediction With Input Identification
NASA Technical Reports Server (NTRS)
Juang, Jer-Nan; Chen, Ya-Chin
1999-01-01
A novel coding technique is presented for signal prediction with applications including speech coding, system identification, and estimation of input excitation. The approach is based on the blind equalization method for speech signal processing in conjunction with the geometric subspace projection theory to formulate the basic prediction equation. The speech-coding problem is often divided into two parts, a linear prediction model and excitation input. The parameter coefficients of the linear predictor and the input excitation are solved simultaneously and recursively by a conventional recursive least-squares algorithm. The excitation input is computed by coding all possible outcomes into a binary codebook. The coefficients of the linear predictor and excitation, and the index of the codebook can then be used to represent the signal. In addition, a variable-frame concept is proposed to block the same excitation signal in sequence in order to reduce the storage size and increase the transmission rate. The results of this work can be easily extended to the problem of disturbance identification. The basic principles are outlined in this report and differences from other existing methods are discussed. Simulations are included to demonstrate the proposed method.
Podoleanu, Adrian Gh; Bradu, Adrian
2013-08-12
Conventional spectral domain interferometry (SDI) methods suffer from the need of data linearization. When applied to optical coherence tomography (OCT), conventional SDI methods are limited in their 3D capability, as they cannot deliver direct en-face cuts. Here we introduce a novel SDI method, which eliminates these disadvantages. We denote this method as Master - Slave Interferometry (MSI), because a signal is acquired by a slave interferometer for an optical path difference (OPD) value determined by a master interferometer. The MSI method radically changes the main building block of an SDI sensor and of a spectral domain OCT set-up. The serially provided signal in conventional technology is replaced by multiple signals, a signal for each OPD point in the object investigated. This opens novel avenues in parallel sensing and in parallelization of signal processing in 3D-OCT, with applications in high- resolution medical imaging and microscopy investigation of biosamples. Eliminating the need of linearization leads to lower cost OCT systems and opens potential avenues in increasing the speed of production of en-face OCT images in comparison with conventional SDI.
Steroid signaling in mature follicles is important for Drosophila ovulation
Knapp, Elizabeth
2017-01-01
Although ecdysteroid signaling regulates multiple steps in oogenesis, it is not known whether it regulates Drosophila ovulation, a process involving a matrix metalloproteinase-dependent follicle rupture. In this study, we demonstrated that ecdysteroid signaling is operating in mature follicle cells to control ovulation. Moreover, knocking down shade (shd), encoding the monooxygenase that converts ecdysone (E) to the more active 20-hydroxyecdysone (20E), specifically in mature follicle cells, blocked follicle rupture, which was rescued by ectopic expression of shd or exogenous 20E. In addition, disruption of the Ecdysone receptor (EcR) in mature follicle cells mimicked shd-knockdown defects, which were reversed by ectopic expression of EcR.B2 but not by EcR.A or EcR.B1 isoforms. Furthermore, we showed that ecdysteroid signaling is essential for the proper activation of matrix metalloproteinase 2 (Mmp2) for follicle rupture. Our data strongly suggest that 20E produced in follicle cells before ovulation activates EcR.B2 to prime mature follicles to be responsive to neuronal ovulatory stimuli, thus providing mechanistic insights into steroid signaling in Drosophila ovulation. PMID:28069934
Panlilio, Leigh V; Thorndike, Eric B; Schindler, Charles W
2007-04-01
According to a recent account of addiction, dopaminergic effects of drugs like cocaine mimic the neuronal signal that occurs when a natural reward has a larger value than expected. Consequently, the drug's expected reward value increases with each administration, leading to an over-selection of drug-seeking behavior. One prediction of this hypothesis is that the blocking effect, a cornerstone of contemporary learning theory, should not occur with drug reinforcers. To test this prediction, two groups of rats were trained to self-administer cocaine with a nose-poking response. For 5 sessions, a tone was paired with each self-administered injection (blocking group), or no stimulus was paired with injection (non-blocking group). Then, in both groups, the tone and a light were both paired with each injection for 5 sessions. In subsequent testing, the light functioned as a conditioned reinforcer for a new response (lever-pressing) in the non-blocking group, but not the blocking group. Thus, contrary to prediction, pre-training with the tone blocked conditioning to the light. Although these results fail to support a potentially powerful explanation of addiction, they are consistent with the fact that most conditioning and learning phenomena that occur with non-drug reinforcers can also be demonstrated with drug reinforcers.
Code of Federal Regulations, 2010 CFR
2010-10-01
... SIGNAL SYSTEM OR RELIEF FROM THE REQUIREMENTS OF PART 236 § 235.1 Scope. This part prescribes application for approval to discontinue or materially modify block signal systems, interlockings, traffic control systems, automatic train stop, train control, or cab signal systems, or other similar appliances, devices...
Benoit, G R; Flexor, M; Besançon, F; Altucci, L; Rossin, A; Hillion, J; Balajthy, Z; Legres, L; Ségal-Bendirdjian, E; Gronemeyer, H; Lanotte, M
2001-07-01
On their own, retinoid X receptor (RXR)-selective ligands (rexinoids) are silent in retinoic acid receptor (RAR)-RXR heterodimers, and no selective rexinoid program has been described as yet in cellular systems. We report here on the rexinoid signaling capacity that triggers apoptosis of immature promyelocytic NB4 cells as a default pathway in the absence of survival factors. Rexinoid-induced apoptosis displays all features of bona fide programmed cell death and is inhibited by RXR, but not RAR antagonists. Several types of survival signals block rexinoid-induced apoptosis. RARalpha agonists switch the cellular response toward differentiation and induce the expression of antiapoptosis factors. Activation of the protein kinase A pathway in the presence of rexinoid agonists induces maturation and blocks immature cell apoptosis. Addition of nonretinoid serum factors also blocks cell death but does not induce cell differentiation. Rexinoid-induced apoptosis is linked to neither the presence nor stability of the promyelocytic leukemia-RARalpha fusion protein and operates also in non-acute promyelocytic leukemia cells. Together our results support a model according to which rexinoids activate in certain leukemia cells a default death pathway onto which several other signaling paradigms converge. This pathway is entirely distinct from that triggered by RAR agonists, which control cell maturation and postmaturation apoptosis.
Inhibition of mutant BRAF splice variant signaling by next-generation, selective RAF inhibitors.
Basile, Kevin J; Le, Kaitlyn; Hartsough, Edward J; Aplin, Andrew E
2014-05-01
Vemurafenib and dabrafenib block MEK-ERK1/2 signaling and cause tumor regression in the majority of advanced-stage BRAF(V600E) melanoma patients; however, acquired resistance and paradoxical signaling have driven efforts for more potent and selective RAF inhibitors. Next-generation RAF inhibitors, such as PLX7904 (PB04), effectively inhibit RAF signaling in BRAF(V600E) melanoma cells without paradoxical effects in wild-type cells. Furthermore, PLX7904 blocks the growth of vemurafenib-resistant BRAF(V600E) cells that express mutant NRAS. Acquired resistance to vemurafenib and dabrafenib is also frequently driven by expression of mutation BRAF splice variants; thus, we tested the effects of PLX7904 and its clinical analog, PLX8394 (PB03), in BRAF(V600E) splice variant-mediated vemurafenib-resistant cells. We show that paradox-breaker RAF inhibitors potently block MEK-ERK1/2 signaling, G1/S cell cycle events, survival and growth of vemurafenib/PLX4720-resistant cells harboring distinct BRAF(V600E) splice variants. These data support the further investigation of paradox-breaker RAF inhibitors as a second-line treatment option for patients failing on vemurafenib or dabrafenib. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Low-Power Embedded DSP Core for Communication Systems
NASA Astrophysics Data System (ADS)
Tsao, Ya-Lan; Chen, Wei-Hao; Tan, Ming Hsuan; Lin, Maw-Ching; Jou, Shyh-Jye
2003-12-01
This paper proposes a parameterized digital signal processor (DSP) core for an embedded digital signal processing system designed to achieve demodulation/synchronization with better performance and flexibility. The features of this DSP core include parameterized data path, dual MAC unit, subword MAC, and optional function-specific blocks for accelerating communication system modulation operations. This DSP core also has a low-power structure, which includes the gray-code addressing mode, pipeline sharing, and advanced hardware looping. Users can select the parameters and special functional blocks based on the character of their applications and then generating a DSP core. The DSP core has been implemented via a cell-based design method using a synthesizable Verilog code with TSMC 0.35[InlineEquation not available: see fulltext.]m SPQM and 0.25[InlineEquation not available: see fulltext.]m 1P5M library. The equivalent gate count of the core area without memory is approximately 50 k. Moreover, the maximum operating frequency of a[InlineEquation not available: see fulltext.] version is 100 MHz (0.35[InlineEquation not available: see fulltext.]m) and 140 MHz (0.25[InlineEquation not available: see fulltext.]m).
Suppression of RIP3-dependent Necroptosis by Human Cytomegalovirus
Omoto, Shinya; Guo, Hongyan; Talekar, Ganesh R.; Roback, Linda; Kaiser, William J.; Mocarski, Edward S.
2015-01-01
Necroptosis is an alternate programmed cell death pathway that is unleashed by caspase-8 compromise and mediated by receptor-interacting protein kinase 3 (RIP3). Murine cytomegalovirus (CMV) and herpes simplex virus (HSV) encode caspase-8 inhibitors that prevent apoptosis together with competitors of RIP homotypic interaction motif (RHIM)-dependent signal transduction to interrupt the necroptosis. Here, we show that pro-necrotic murine CMV M45 mutant virus drives virus-induced necroptosis during nonproductive infection of RIP3-expressing human fibroblasts, whereas WT virus does not. Thus, M45-encoded RHIM competitor, viral inhibitor of RIP activation, sustains viability of human cells like it is known to function in infected mouse cells. Importantly, human CMV is shown to block necroptosis induced by either TNF or M45 mutant murine CMV in RIP3-expressing human cells. Human CMV blocks TNF-induced necroptosis after RIP3 activation and phosphorylation of the mixed lineage kinase domain-like (MLKL) pseudokinase. An early, IE1-regulated viral gene product acts on a necroptosis step that follows MLKL phosphorylation prior to membrane leakage. This suppression strategy is distinct from RHIM signaling competition by murine CMV or HSV and interrupts an execution process that has not yet been fully elaborated. PMID:25778401
49 CFR 236.567 - Restrictions imposed when device fails and/or is cut out en route.
Code of Federal Regulations, 2011 CFR
2011-10-01
... GOVERNING THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Train Stop, Train Control and Cab Signal Systems Rules and Instructions... restricted speed or if an automatic block signal system is in operation according to signal indication but...
Federal Register 2010, 2011, 2012, 2013, 2014
2013-09-27
... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... of a signal system. FRA assigned the petition Docket Number FRA-2013-0095. Applicant: Grenada Railway... seeks approval of the proposed discontinuance and removal of the automatic block signal (ABS) system...
Federal Register 2010, 2011, 2012, 2013, 2014
2012-02-16
... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... or modification of a signal system. FRA assigned the petition Docket Number FRA-2012-0012. UP seeks approval of the proposed discontinuance of the automatic block signal (ABS) system between Control Point...
Laser Studies of Gas Phase Radical Reactions.
1989-01-01
synchronised chopper ( Rofin 7500) to block the laser beam on alternate shots to allow background subtraction. Signal due to scattered laser light was...synchronised chopper ( Rofin 7500) to block the laser beam on alternate shots to allow background subtraction. Signal due to scattered laser light was...Cassufication) (U) Laser Studies of Gas Phase Radical Reactions ,ERSRP4AL UTHOR($) I3a. TYPE Of REPORT 13b. TIME COVERtD 14 D T8?’F JPORT (Year, Maonlth, Da
... a part of the heart that carries the signals that control the time between heartbeats (contractions). ... through the center of the heart. If these signals are blocked, you will have problems with your ...
Nishigaki, Kazuo; Hanson, Charlotte; Ohashi, Takashi; Spadaccini, Angelo; Ruscetti, Sandra
2006-01-01
Infection of mice with Friend spleen focus-forming virus (SFFV) results in a multistage erythroleukemia. In the first stage, the SFFV envelope glycoprotein interacts with the erythropoietin receptor and a short form of the receptor tyrosine kinase sf-Stk, resulting in constitutive activation of signal transducing molecules and the development of erythropoietin (Epo)-independent erythroid hyperplasia and polycythemia. The second stage results from the outgrowth of a rare virus-infected erythroid cell that expresses nonphysiological levels of the myeloid transcription factor PU.1. These cells exhibit a differentiation block and can be grown as murine erythroleukemia (MEL) cell lines. In this study, we examined SFFV MEL cells to determine whether their transformed phenotype was associated with a block in the activation of any Epo signal-transducing molecules. Our studies indicate that Epo- or SFFV-induced activation of STAT1/3 DNA binding activity is blocked in SFFV MEL cells. The block is at the level of tyrosine phosphorylation of STAT1, although Jak2 phosphorylation is not blocked in these cells. In contrast to Epo, alpha interferon can induce STAT1 phosphorylation and DNA binding in SFFV MEL cells. The SFFV-transformed cells were shown to express elevated levels of the hematopoietic phosphatase SHP-1, and treatment of the cells with a phosphatase inhibitor restored STAT1 tyrosine phosphorylation. MEL cells derived from Friend murine leukemia virus (MuLV) or ME26 MuLV-infected mice, which do not express PU.1, express lower levels of SHP-1 and are not blocked in STAT1/3 DNA-binding activity. Our studies suggest that SFFV-infected erythroid cells become transformed when differentiation signals activated by STAT1/3 are blocked due to high SHP-1 levels induced by inappropriate expression of the PU.1 protein. PMID:16731906
... turn off" a pain signal along a specific distribution of nerve. Imaging guidance may be used to place the needle in the most appropriate location for maximum benefit. A nerve block may allow a damaged nerve time to heal, provide temporary pain relief and help ...
Non-neural BOLD variability in block and event-related paradigms.
Kannurpatti, Sridhar S; Motes, Michael A; Rypma, Bart; Biswal, Bharat B
2011-01-01
Block and event-related stimulus designs are typically used in fMRI studies depending on the importance of detection power or estimation efficiency. The extent of vascular contribution to variability in block and event-related fMRI-BOLD response is not known. With scaling, the extent of vascular variability in the fMRI-BOLD response during block and event-related design tasks was investigated. Blood oxygen level-dependent (BOLD) contrast data from healthy volunteers performing a block design motor task and an event-related memory task requiring performance of a motor response were analyzed from the regions of interest (ROIs) surrounding the primary and supplementary motor cortices. Average BOLD signal change was significantly larger during the block design compared to the event-related design. In each subject, BOLD signal change across voxels in the ROIs had higher variation during the block design task compared to the event-related design task. Scaling using the resting state fluctuation of amplitude (RSFA) and breath-hold (BH), which minimizes BOLD variation due to vascular origins, reduced the within-subject BOLD variability in every subject during both tasks but significantly reduced BOLD variability across subjects only during the block design task. The strong non-neural source of intra- and intersubject variability of BOLD response during the block design compared to event-related task indicates that study designs optimizing for statistical power through enhancement of the BOLD contrast (for, e.g., block design) can be affected by enhancement of non-neural sources of BOLD variability. Copyright © 2011. Published by Elsevier Inc.
Switching Matrix For Optical Signals
NASA Technical Reports Server (NTRS)
Grove, Charles H.
1990-01-01
Proposed matrix of electronically controlled shutters switches signals in optical fibers between multiple input and output channels. Size, weight, and power consumption reduced. Device serves as building block for small, low-power, broad-band television- and data-signal-switching systems providing high isolation between nominally disconnected channels.
Mechanical signaling coordinates the embryonic heart
NASA Astrophysics Data System (ADS)
Chiou, Kevin; Rocks, Jason; Prosser, Benjamin; Discher, Dennis; Liu, Andrea
The heart is an active material which relies on robust signaling mechanisms between cells in order to produce well-timed, coordinated beats. Heart tissue is composed primarily of active heart muscle cells (cardiomyocytes) embedded in a passive extracellular matrix. During a heartbeat, cardiomyocyte contractions are coordinated across the heart to form a wavefront that propagates through the tissue to pump blood. In the adult heart, this contractile wave is coordinated via intercellular electrical signaling.Here we present theoretical and experimental evidence for mechanical coordination of embryonic heartbeats. We model cardiomyocytes as mechanically excitable Eshelby inclusions embedded in an overdamped elastic-fluid biphasic medium. For physiological parameters, this model replicates recent experimental measurements of the contractile wavefront which are not captured by electrical signaling models. We additionally challenge our model by pharmacologically blocking gap junctions, inhibiting electrical signaling between myocytes. We find that while adult hearts stop beating almost immediately after gap junctions are blocked, embryonic hearts continue beating even at significantly higher concentrations, providing strong support for a mechanical signaling mechanism.
Jin, Lian; Qin, Qingqing; Wang, Yu; Pu, Yingying; Liu, Lifang; Wen, Xing; Ji, Shaoyi; Wu, Jianguo; Wei, Chunhong; Li, Yi
2016-01-01
The phytohormone auxin plays critical roles in regulating myriads of plant growth and developmental processes. Microbe infection can disturb auxin signaling resulting in defects in these processes, but the underlying mechanisms are poorly understood. Auxin signaling begins with perception of auxin by a transient co-receptor complex consisting of an F-box transport inhibitor response 1/auxin signaling F-box (TIR1/AFB) protein and an auxin/indole-3-acetic acid (Aux/IAA) protein. Auxin binding to the co-receptor triggers ubiquitination and 26S proteasome degradation of the Aux/IAA proteins, leading to subsequent events, including expression of auxin-responsive genes. Here we report that Rice dwarf virus (RDV), a devastating pathogen of rice, causes disease symptoms including dwarfing, increased tiller number and short crown roots in infected rice as a result of reduced sensitivity to auxin signaling. The RDV capsid protein P2 binds OsIAA10, blocking the interaction between OsIAA10 and OsTIR1 and inhibiting 26S proteasome-mediated OsIAA10 degradation. Transgenic rice plants overexpressing wild-type or a dominant-negative (degradation-resistant) mutant of OsIAA10 phenocopy RDV symptoms are more susceptible to RDV infection; however, knockdown of OsIAA10 enhances the resistance of rice to RDV infection. Our findings reveal a previously unknown mechanism of viral protein reprogramming of a key step in auxin signaling initiation that enhances viral infection and pathogenesis. PMID:27606959
Bussiere, Renaud; Lacampagne, Alain; Reiken, Steven; Liu, Xiaoping; Scheuerman, Valerie; Zalk, Ran; Martin, Cécile; Checler, Frederic; Marks, Andrew R; Chami, Mounia
2017-06-16
Alteration of ryanodine receptor (RyR)-mediated calcium (Ca 2+ ) signaling has been reported in Alzheimer disease (AD) models. However, the molecular mechanisms underlying altered RyR-mediated intracellular Ca 2+ release in AD remain to be fully elucidated. We report here that RyR2 undergoes post-translational modifications (phosphorylation, oxidation, and nitrosylation) in SH-SY5Y neuroblastoma cells expressing the β-amyloid precursor protein (βAPP) harboring the familial double Swedish mutations (APPswe). RyR2 macromolecular complex remodeling, characterized by depletion of the regulatory protein calstabin2, resulted in increased cytosolic Ca 2+ levels and mitochondrial oxidative stress. We also report a functional interplay between amyloid β (Aβ), β-adrenergic signaling, and altered Ca 2+ signaling via leaky RyR2 channels. Thus, post-translational modifications of RyR occur downstream of Aβ through a β2-adrenergic signaling cascade that activates PKA. RyR2 remodeling in turn enhances βAPP processing. Importantly, pharmacological stabilization of the binding of calstabin2 to RyR2 channels, which prevents Ca 2+ leakage, or blocking the β2-adrenergic signaling cascade reduced βAPP processing and the production of Aβ in APPswe-expressing SH-SY5Y cells. We conclude that targeting RyR-mediated Ca 2+ leakage may be a therapeutic approach to treat AD. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Intersecting Roles of Protein Tyrosine Kinase and Calcium Signaling During Fertilization
Kinsey, William H.
2012-01-01
The oocyte is a highly specialized cell that must respond to fertilization with a preprogrammed series of signal transduction events that establish a block to polyspermy, trigger resumption of the cell cycle and execution of a developmental program. The fertilization-induced calcium transient is a key signal that initiates the process of oocyte activation and studies over the last several years have examined the signaling pathways that act upstream and downstream of this calcium transient. Protein tyrosine kinase signaling was found to be an important component of the upstream pathways that stimulated calcium release at fertilization in oocytes from animals that fertilize externally, but a similar pathway has not been found in mammals which fertilize internally. The following review will examine the diversity of signaling in oocytes from marine invertebrates, amphibians, fish and mammals in an attempt to understand the basis for the observed differences. In addition to the pathways upstream of the fertilization-induced calcium transient, recent studies are beginning to unravel the role of protein tyrosine kinase signaling downstream of the calcium transient. The PYK2 kinase was found to respond to fertilization in the zebrafish system and seems to represent a novel component of the response of the oocyte to fertilization. The potential impact of impaired PTK signaling in oocyte quality will also be discussed. PMID:23201334
Wnt/β-Catenin Signaling Determines the Vasculogenic Fate of Postnatal Mesenchymal Stem Cells.
Zhang, Zhaocheng; Nör, Felipe; Oh, Min; Cucco, Carolina; Shi, Songtao; Nör, Jacques E
2016-06-01
Vasculogenesis is the process of de novo blood vessel formation observed primarily during embryonic development. Emerging evidence suggest that postnatal mesenchymal stem cells are capable of recapitulating vasculogenesis when these cells are engaged in tissue regeneration. However, the mechanisms underlining the vasculogenic differentiation of mesenchymal stem cells remain unclear. Here, we used stem cells from human permanent teeth (dental pulp stem cells [DPSC]) or deciduous teeth (stem cells from human exfoliated deciduous teeth [SHED]) as models of postnatal primary human mesenchymal stem cells to understand mechanisms regulating their vasculogenic fate. GFP-tagged mesenchymal stem cells seeded in human tooth slice/scaffolds and transplanted into immunodeficient mice differentiate into human blood vessels that anastomize with the mouse vasculature. In vitro, vascular endothelial growth factor (VEGF) induced the vasculogenic differentiation of DPSC and SHED via potent activation of Wnt/β-catenin signaling. Further, activation of Wnt signaling is sufficient to induce the vasculogenic differentiation of postnatal mesenchymal stem cells, while Wnt inhibition blocked this process. Notably, β-catenin-silenced DPSC no longer differentiate into endothelial cells in vitro, and showed impaired vasculogenesis in vivo. Collectively, these data demonstrate that VEGF signaling through the canonical Wnt/β-catenin pathway defines the vasculogenic fate of postnatal mesenchymal stem cells. Stem Cells 2016;34:1576-1587. © 2016 AlphaMed Press.
Bisson, Melanie M A; Groth, Georg
2015-08-01
The gaseous plant hormone ethylene regulates many processes of high agronomic relevance throughout the life span of plants. A central element in ethylene signaling is the endoplasmic reticulum (ER)-localized membrane protein ethylene insensitive2 (EIN2). Recent studies indicate that in response to ethylene, the extra-membranous C-terminal end of EIN2 is proteolytically processed and translocated from the ER to the nucleus. Here, we report that the conserved nuclear localization signal (NLS) mediating nuclear import of the EIN2 C-terminus provides an important domain for complex formation with ethylene receptor ethylene response1 (ETR1). EIN2 lacking the NLS domain shows strongly reduced affinity for the receptor. Interaction of EIN2 and ETR1 is also blocked by a synthetic peptide of the NLS motif. The corresponding peptide substantially reduces ethylene responses in planta. Our results uncover a novel mechanism and type of inhibitor interfering with ethylene signal transduction and ethylene responses in plants. Disruption of essential protein-protein interactions in the ethylene signaling pathway as shown in our study for the EIN2-ETR1 complex has the potential to guide the development of innovative ethylene antagonists for modern agriculture and horticulture. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.
Chandramohan, Yalini; Droste, Susanne K; Arthur, J Simon C; Reul, Johannes M H M
2008-05-01
The hippocampus is involved in learning and memory. Previously, we have shown that the acquisition of the behavioural immobility response after a forced swim experience is associated with chromatin modifications and transcriptional induction in dentate gyrus granule neurons. Given that both N-methyl-D-aspartate (NMDA) receptors and the extracellular signal-regulated kinases (ERK) 1/2 signalling pathway are involved in neuroplasticity processes underlying learning and memory, we investigated in rats and mice whether these signalling pathways regulate chromatin modifications and transcriptional events participating in the acquisition of the immobility response. We found that: (i) forced swimming evoked a transient increase in the number of phospho-acetylated histone H3-positive [P(Ser10)-Ac(Lys14)-H3(+)] neurons specifically in the middle and superficial aspects of the dentate gyrus granule cell layer; (ii) antagonism of NMDA receptors and inhibition of ERK1/2 signalling blocked forced swimming-induced histone H3 phospho-acetylation and the acquisition of the behavioural immobility response; (iii) double knockout (DKO) of the histone H3 kinase mitogen- and stress-activated kinases (MSK) 1/2 in mice completely abolished the forced swimming-induced increases in histone H3 phospho-acetylation and c-Fos induction in dentate granule neurons and the behavioural immobility response; (iv) blocking mineralocorticoid receptors, known not to be involved in behavioural immobility in the forced swim test, did not affect forced swimming-evoked histone H3 phospho-acetylation in dentate neurons; and (v) the pharmacological manipulations and gene deletions did not affect behaviour in the initial forced swim test. We conclude that the forced swimming-induced behavioural immobility response requires histone H3 phospho-acetylation and c-Fos induction in distinct dentate granule neurons through recruitment of the NMDA/ERK/MSK 1/2 pathway.
Acute myotube protein synthesis regulation by IL-6-related cytokines.
Gao, Song; Durstine, J Larry; Koh, Ho-Jin; Carver, Wayne E; Frizzell, Norma; Carson, James A
2017-11-01
IL-6 and leukemia inhibitory factor (LIF), members of the IL-6 family of cytokines, play recognized paradoxical roles in skeletal muscle mass regulation, being associated with both growth and atrophy. Overload or muscle contractions can induce a transient increase in muscle IL-6 and LIF expression, which has a regulatory role in muscle hypertrophy. However, the cellular mechanisms involved in this regulation have not been completely identified. The induction of mammalian target of rapamycin complex 1 (mTORC1)-dependent myofiber protein synthesis is an established regulator of muscle hypertrophy, but the involvement of the IL-6 family of cytokines in this process is poorly understood. Therefore, we investigated the acute effects of IL-6 and LIF administration on mTORC1 signaling and protein synthesis in C2C12 myotubes. The role of glycoprotein 130 (gp130) receptor and downstream signaling pathways, including phosphoinositide 3-kinase (PI3K)-Akt-mTORC1 and signal transducer and activator of transcription 3 (STAT3)-suppressor of cytokine signaling 3 (SOCS3), was investigated by administration of specific siRNA or pharmaceutical inhibitors. Acute administration of IL-6 and LIF induced protein synthesis, which was accompanied by STAT3 activation, Akt-mTORC1 activation, and increased SOCS3 expression. This induction of protein synthesis was blocked by both gp130 siRNA knockdown and Akt inhibition. Interestingly, STAT3 inhibition or Akt downstream mTORC1 signaling inhibition did not fully block the IL-6 or LIF induction of protein synthesis. SOCS3 siRNA knockdown increased basal protein synthesis and extended the duration of the protein synthesis induction by IL-6 and LIF. These results demonstrate that either IL-6 or LIF can activate gp130-Akt signaling axis, which induces protein synthesis via mTORC1-independent mechanisms in cultured myotubes. However, IL-6- or LIF-induced SOCS3 negatively regulates the activation of myotube protein synthesis. Copyright © 2017 the American Physiological Society.
A low-power small-area ADC array for IRFPA readout
NASA Astrophysics Data System (ADS)
Zhong, Shengyou; Yao, Libin
2013-09-01
The readout integrated circuit (ROIC) is a bridge between the infrared focal plane array (IRFPA) and image processing circuit in an infrared imaging system. The ROIC is the first part of signal processing circuit and connected to detectors directly, so its performance will greatly affect the detector or even the whole imaging system performance. With the development of CMOS technologies, it's possible to digitalize the signal inside the ROIC and develop the digital ROIC. Digital ROIC can reduce complexity of the whole system and improve the system reliability. More importantly, it can accommodate variety of digital signal processing techniques which the traditional analog ROIC cannot achieve. The analog to digital converter (ADC) is the most important building block in the digital ROIC. The requirements for ADCs inside the ROIC are low power, high dynamic range and small area. In this paper we propose an RC hybrid Successive Approximation Register (SAR) ADC as the column ADC for digital ROIC. In our proposed ADC structure, a resistor ladder is used to generate several voltages. The proposed RC hybrid structure not only reduces the area of capacitor array but also releases requirement for capacitor array matching. Theory analysis and simulation show RC hybrid SAR ADC is suitable for ADC array applications
LDPC-PPM Coding Scheme for Optical Communication
NASA Technical Reports Server (NTRS)
Barsoum, Maged; Moision, Bruce; Divsalar, Dariush; Fitz, Michael
2009-01-01
In a proposed coding-and-modulation/demodulation-and-decoding scheme for a free-space optical communication system, an error-correcting code of the low-density parity-check (LDPC) type would be concatenated with a modulation code that consists of a mapping of bits to pulse-position-modulation (PPM) symbols. Hence, the scheme is denoted LDPC-PPM. This scheme could be considered a competitor of a related prior scheme in which an outer convolutional error-correcting code is concatenated with an interleaving operation, a bit-accumulation operation, and a PPM inner code. Both the prior and present schemes can be characterized as serially concatenated pulse-position modulation (SCPPM) coding schemes. Figure 1 represents a free-space optical communication system based on either the present LDPC-PPM scheme or the prior SCPPM scheme. At the transmitting terminal, the original data (u) are processed by an encoder into blocks of bits (a), and the encoded data are mapped to PPM of an optical signal (c). For the purpose of design and analysis, the optical channel in which the PPM signal propagates is modeled as a Poisson point process. At the receiving terminal, the arriving optical signal (y) is demodulated to obtain an estimate (a^) of the coded data, which is then processed by a decoder to obtain an estimate (u^) of the original data.
NASA Astrophysics Data System (ADS)
Bhadra, Narendra; Foldes, Emily; Vrabec, Tina; Kilgore, Kevin; Bhadra, Niloy
2018-02-01
Objective. Application of kilohertz frequency alternating current (KHFAC) waveforms can result in nerve conduction block that is induced in less than a second. Conduction recovers within seconds when KHFAC is applied for about 5-10 min. This study investigated the effect of repeated and prolonged application of KHFAC on rat sciatic nerve with bipolar platinum electrodes. Approach. Varying durations of KHFAC at signal amplitudes for conduction block with intervals of no stimulus were studied. Nerve conduction was monitored by recording peak Gastrocnemius muscle force utilizing stimulation electrodes proximal (PS) and distal (DS) to a blocking electrode. The PS signal traveled through the block zone on the nerve, while the DS went directly to the motor end-plate junction. The PS/DS force ratio provided a measure of conduction patency of the nerve in the block zone. Main results. Conduction recovery times were found to be significantly affected by the cumulative duration of KHFAC application. Peak stimulated muscle force returned to pre-block levels immediately after cessation of KHFAC delivery when it was applied for less than about 15 min. They fell significantly but recovered to near pre-block levels for cumulative stimulus of 50 ± 20 min, for the tested On/Off times and frequencies. Conduction recovered in two phases, an initial fast one (60-80% recovery), followed by a slower phase. No permanent conduction block was seen at the end of the observation period during any experiment. Significance. This carry-over block effect may be exploited to provide continuous conduction block in peripheral nerves without continuous application of KHFAC.
Spectral analysis of temporal non-stationary rainfall-runoff processes
NASA Astrophysics Data System (ADS)
Chang, Ching-Min; Yeh, Hund-Der
2018-04-01
This study treats the catchment as a block box system with considering the rainfall input and runoff output being a stochastic process. The temporal rainfall-runoff relationship at the catchment scale is described by a convolution integral on a continuous time scale. Using the Fourier-Stieltjes representation approach, a frequency domain solution to the convolution integral is developed to the spectral analysis of runoff processes generated by temporal non-stationary rainfall events. It is shown that the characteristic time scale of rainfall process increases the runoff discharge variability, while the catchment mean travel time constant plays the role in reducing the variability of runoff discharge. Similar to the behavior of groundwater aquifers, catchments act as a low-pass filter in the frequency domain for the rainfall input signal.
Wu, Di; Liu, Na; Liu, Qing-Feng; Wu, Qiu-Wan; Xie, Yuan-Yuan; Liu, Yun-Jia; Zheng, Zhong-Zheng; Chan, Err-Cheng; Zhang, Zhi-Ming; Li, Bo-An
2017-01-01
Great progress has been achieved in the study of the role of TGF-β signaling in triggering epithelial-mesenchymal transition (EMT) in a variety of cancers; however, the regulation of TGF-β signaling during EMT in mammary tumor metastasis has not been completely defined. In the present study, we demonstrated that OVOL2, a zinc finger transcription factor, inhibits TGF-β signaling-induced EMT in mouse and human mammary tumor cells, as well as in mouse tumor models. Data from the Oncomine databases indicated a strong negative relationship between OVOL2 expression and breast cancer progression. Moreover, our experiments revealed that OVOL2 inhibits TGF-β signaling at multiple levels, including inhibiting Smad4 mRNA expression and inducing Smad7 mRNA expression, blocking the binding between Smad4 and target DNA, and interfering with complex formation between Smad4 and Smad2/3. These findings reveal a novel mechanism that controls the TGF-β signaling output level in vitro and in vivo. The modulation of these molecular processes may represent a strategy for inhibiting breast cancer invasion by restoring OVOL2 expression. PMID:28455959
Correlator data analysis for the array feed compensation system
NASA Technical Reports Server (NTRS)
Iijima, B.; Fort, D.; Vilnrotter, V.
1994-01-01
The real-time array feed compensation system is currently being evaluated at DSS 13. This system recovers signal-to-noise ratio (SNR) loss due to mechanical antenna deformations by using an array of seven Ka-band (33.7-GHz) horns to collect the defocused signal fields. The received signals are downconverted and digitized, in-phase and quadrature samples are generated, and combining weights are applied before the samples are recombined. It is shown that when optimum combining weights are employed, the SNR of the combined signal approaches the sum of the channel SNR's. The optimum combining weights are estimated directly from the signals in each channel by the Real-Time Block 2 (RTB2) correlator; since it was designed for very-long-baseline interferometer (VLBI) applications, it can process broadband signals as well as tones to extract the required weight estimates. The estimation algorithms for the optimum combining weights are described for tones and broadband sources. Data recorded in correlator output files can also be used off-line to estimate combiner performance by estimating the SNR in each channel, which was done for data taken during a Jupiter track at DSS 13.
Chemico-Genetic Identification of Drebrin as a Regulator of Calcium Responses
Mercer, Jason C.; Qi, Qian; Mottram, Laurie F.; Law, Mankit; Bruce, Danny; Iyer, Archana; Morales, J. Luis; Yamazaki, Hiroyuki; Shirao, Tomoaki; Peterson, Blake R.; August, Avery
2009-01-01
Store-operated calcium channels are plasma membrane Ca2+ channels that are activated by depletion of intracellular Ca2+ stores, resulting in an increase in intracellular Ca2+ concentration, which is maintained for prolonged periods in some cell types. Increases in intracellular Ca2+ concentration serve as signals that activate a number of cellular processes, however, little is known about the regulation of these channels. We have characterized the immuno-suppressant compound BTP, which blocks store-operated channel mediated calcium influx into cells. Using an affinity purification scheme to identify potential targets of BTP, we identified the actin reorganizing protein, drebrin, and demonstrated that loss of drebrin protein expression prevents store-operated channel mediated Ca2+ entry, similar to BTP treatment. BTP also blocks actin rearrangements induced by drebrin. While actin cytoskeletal reorganization has been implicated in store-operated calcium channel regulation, little is known about actin binding proteins that are involved in this process, or how actin regulates channel function. The identification of drebrin as a mediator of this process should provide new insight into the interaction between actin rearrangement and tore-operated channel mediated calcium influx. PMID:19948240
Cyclic GMP is involved in auxin signalling during Arabidopsis root growth and development.
Nan, Wenbin; Wang, Xiaomin; Yang, Lei; Hu, Yanfeng; Wei, Yuantao; Liang, Xiaolei; Mao, Lina; Bi, Yurong
2014-04-01
The second messenger cyclic guanosine 3',5'-monophosphate (cGMP) plays an important role in plant development and responses to stress. Recent studies indicated that cGMP is a secondary signal generated in response to auxin stimulation. cGMP also mediates auxin-induced adventitious root formation in mung bean and gravitropic bending in soybean. Nonetheless, the mechanism of the participation of cGMP in auxin signalling to affect these growth and developmental processes is largely unknown. In this report we provide evidence that indole-3-acetic acid (IAA) induces cGMP accumulation in Arabidopsis roots through modulation of the guanylate cyclase activity. Application of 8-bromo-cGMP (a cell-permeable cGMP derivative) increases auxin-dependent lateral root formation, root hair development, primary root growth, and gene expression. In contrast, inhibitors of endogenous cGMP synthesis block these processes induced by auxin. Data also showed that 8-bromo-cGMP enhances auxin-induced degradation of Aux/IAA protein modulated by the SCF(TIR1) ubiquitin-proteasome pathway. Furthermore, it was found that 8-bromo-cGMP is unable to directly influence the auxin-dependent TIR1-Aux/IAA interaction as evidenced by pull-down and yeast two-hybrid assays. In addition, we provide evidence for cGMP-mediated modulation of auxin signalling through cGMP-dependent protein kinase (PKG). Our results suggest that cGMP acts as a mediator to participate in auxin signalling and may govern this process by PKG activity via its influence on auxin-regulated gene expression and auxin/IAA degradation.
Fiala, Milan
2015-02-12
STAT-3 and STAT-1 signaling have opposite effects in oncogenesis with STAT-3 acting as an oncogene and STAT-1 exerting anti-oncogenic activities through interferon-γ and interferon-α. The cytokine IL-6 promotes oncogenesis by stimulation of NFκB and STAT-3 signaling. Curcuminoids have bi-functional effects by blocking NFκB anti-apoptotic signaling but also blocking anti-oncogenic STAT-1 signaling and interferon-γ production. In our recent study (unpublished work [1]) in pancreatic cancer cell cultures, curcuminoids enhanced cancer cell apoptosis both directly and by potentiating natural killer (NK) cell cytotoxic function. The cytotoxic effects of curcuminoids were increased by incubation of cancer cells and NK cells in an emulsion with omega-3 fatty acids and antioxidants (Smartfish), which enhanced cancer cell apoptosis and protected NK cells against degradation. However, as also shown by others, curcuminoids blocked interferon-γ production by NK cells. The combined use of curcuminoids and omega-3 in cancer immunotherapy will require deeper understanding of their in vivo interactions with the immune system.
Universal Strategy To Reduce Noise Current for Sensitive Organic Photodetectors.
Xiong, Sixing; Li, Lingliang; Qin, Fei; Mao, Lin; Luo, Bangwu; Jiang, Youyu; Li, Zaifang; Huang, Jinsong; Zhou, Yinhua
2017-03-15
Low noise current is critical for achieving high-detectivity organic photodetectors. Inserting charge-blocking layers is an effective approach to suppress the reverse-biased dark current. However, in solution-processed organic photodetectors, the charge-transport material needs to be dissolved in solvents that do not dissolve the underneath light-absorbing layer, which is not always possible for all kinds of light-absorbing materials developed. Here, we introduce a universal strategy of transfer-printing a conjugated polymer, poly(3-hexylthiophene) (P3HT), as the electron-blocking layer to realize highly sensitive photodetectors. The transfer-printed P3HT layers substantially and universally reduced the reverse-biased dark current by about 3 orders of magnitude for various photodetectors with different active layers. These photodetectors can detect the light signal as weak as several picowatts per square centimeter, and the device detectivity is over 10 12 Jones. The results suggest that the strategy of transfer-printing P3HT films as the electron-blocking layer is universal and effective for the fabrication of sensitive organic photodetectors.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-04-19
... Discontinuance or Modification of a Railroad Signal System Pursuant to Title 49 Code of Federal Regulations (CFR... Administration (FRA) seeking approval for the discontinuance or modification of the signal system, as detailed... block signal system (ABS) on three sections of the Roseburg Subdivision and on one section of the...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-06-16
... of Application for Approval of Discontinuance or Modification of a Railroad Signal System Pursuant to... of the signal, as detailed below. Docket Number: FRA-2010-0084. Applicant: Pan Am Railways, Mr... CPF-428, all associated appliances, and the installation of an automatic block signal at mile 428.27...
Huang, Yu; Chen, Zhiying; Jang, Joon Hee; Baig, Mirza S; Bertolet, Grant; Schroeder, Casey; Huang, Shengjian; Hu, Qian; Zhao, Yong; Lewis, Dorothy E; Qin, Lidong; Zhu, Michael Xi; Liu, Dongfang
2018-04-18
The inhibitory receptor programmed cell death protein 1 (PD-1) is upregulated on a variety of immune cells, including natural killer (NK) cells, during chronic viral infection and tumorigenesis. Blockade of PD-1 or its ligands produces durable clinical responses with tolerable side effects in patients with a broad spectrum of cancers. However, the underlying molecular mechanisms of how PD-1 regulates NK cell function remain poorly characterized. We sought to determine the effect of PD-1 signaling on NK cells. PD-1 was overexpressed in CD16-KHYG-1 (a human NK cell line with both antibody-dependent cellular cytotoxicity through CD16 and natural cytotoxicity through NKG2D) cells and stimulated by exposing the cells to NK-sensitive target cells expressing programmed death ligand 1 (PD-L1). PD-1 engagement by PD-L1 specifically blocked NK cell-mediated cytotoxicity without interfering with the conjugation between NK cells and target cells. Further examination showed that PD-1 signaling blocked lytic granule polarization in NK cells, which was accompanied by failure of integrin-linked kinase, a key molecule in the integrin outside-in signaling pathway, to accumulate in the immunological synapse after NK-target cell conjugation. Our results suggest that NK cell cytotoxicity is inhibited by PD-1 engagement, which blocks lytic granule polarization to the NK cell immunological synapse with concomitant impairment of integrin outside-in signaling. This study provides novel mechanistic insights into how PD-1 inhibition disrupts NK cell function. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
NO and H2O2 contribute to SO2 toxicity via Ca2+ signaling in Vicia faba guard cells.
Yi, Min; Bai, Heli; Xue, Meizhao; Yi, Huilan
2017-04-01
NO and H 2 O 2 have been implicated as important signals in biotic and abiotic stress responses of plants to the environment. Previously, we have shown that SO 2 exposure increased the levels of NO and H 2 O 2 in plant cells. We hypothesize that, as signaling molecules, NO and H 2 O 2 mediate SO 2 -caused toxicity. In this paper, we show that SO 2 hydrates caused guard cell death in a concentration-dependent manner in the concentration range of 0.25 to 6 mmol L -1 , which was associated with elevation of intracellular NO, H 2 O 2 , and Ca 2+ levels in Vicia faba guard cells. NO donor SNP enhanced SO 2 toxicity, while NO scavenger c-PTIO and NO synthesis inhibitors L-NAME and tungstate significantly prevented SO 2 toxicity. ROS scavenger ascorbic acid (AsA) and catalase (CAT), Ca 2+ chelating agent EGTA, and Ca 2+ channel inhibitor LaCl 3 also markedly blocked SO 2 toxicity. In addition, both c-PTIO and AsA could completely block SO 2 -induced elevation of intracellular Ca 2+ level. Moreover, c-PTIO efficiently blocked SO 2 -induced H 2 O 2 elevation, and AsA significantly blocked SO 2 -induced NO elevation. These results indicate that extra NO and H 2 O 2 are produced and accumulated in SO 2 -treated guard cells, which further activate Ca 2+ signaling to mediate SO 2 toxicity. Our findings suggest that both NO and H 2 O 2 contribute to SO 2 toxicity via Ca 2+ signaling.
Krishnan, Balaji; Scott, Michael T.; Pollandt, Sebastian; Schroeder, Bradley; Kurosky, Alexander; Shinnick-Gallagher, Patricia
2016-01-01
Long-term memory (LTM) of fear stores activity dependent modifications that include changes in amygdala signaling. Previously, we identified an enhanced probability of release of glutamate mediated signaling to be important in rat fear potentiated startle (FPS), a well-established translational behavioral measure of fear. Here, we investigated short- and long-term synaptic plasticity in FPS involving metabotropic glutamate receptors (mGluRs) and associated downstream proteomic changes in the thalamic-lateral amygdala pathway (Th-LA). Aldolase A, an inhibitor of phospholipase D (PLD), expression was reduced, concurrent with significantly elevated PLD protein expression. Blocking the PLD-mGluR signaling significantly reduced PLD activity. While transmitter release probability increased in FPS, PLD-mGluR agonist and antagonist actions were occluded. In the unpaired group (UNP), blocking the PLD-mGluR increased while activating the receptor decreased transmitter release probability, consistent with decreased synaptic potentials during tetanic stimulation. FPS Post-tetanic potentiation (PTP) immediately following long-term potentiation (LTP) induction was significantly increased. Blocking PLD-mGluR signaling prevented PTP and reduced cumulative PTP probability but not LTP maintenance in both groups. These effects are similar to those mediated through mGluR7, which is co-immunoprecipitated with PLD in FPS. Lastly, blocking mGluR-PLD in the rat amygdala was sufficient to prevent behavioral expression of fear memory. Thus, our study in the Th-LA pathway provides the first evidence for PLD as an important target of mGluR signaling in amygdala fear-associated memory. Importantly, the PLD-mGluR provides a novel therapeutic target for treating maladaptive fear memories in posttraumatic stress and anxiety disorders. PMID:26748024
Centering a DDR Strobe in the Middle of a Data Packet
NASA Technical Reports Server (NTRS)
Johnson, Michael; Nelson, Dave; Seefeldt, James; Roper, Weston; Passow, Craig
2014-01-01
The Orion CEV Northstar ASIC (application- specific integrated circuit) project required a DDR (double data rate) memory bus driver/receiver (DDR PHY block) to interface with external DDR memory. The DDR interface (JESD79C) is based on a source synchronous strobe (DQS\\) that is sent along with each packet of data (DQ). New data is provided concurrently with each edge of strobe and is sent irregularly. In order to capture this data, the strobe needs to be delayed and used to latch the data into a register. A circuit solves the need for training a DDR PRY block by incorporating a PVT-compensated delay element in the strobe path. This circuit takes an external reference clock signal and uses the regular clock to calibrate a known delay through a data path. The compensated delay DQS signal is then used to capture the DQ data in a normal register. This register structure can be configured as a FIFO (first in first out), in order to transfer data from the DDR domain to the system clock domain. This design is different in that it does not rely upon the need for training the system response, nor does it use a PLL (phase locked loop) or a DLL (delay locked loop) to provide an offset of the strobe signal. The circuit is created using standard ASIC building blocks, plus the PVT (process, voltage, and temperature) compensated delay line. The design uses a globally available system clock as a reference, alleviating the need to operate synchronously with the remote memory. The reference clock conditions the PVT compensated delay line to provide a pre-determined amount of delay to any data signal that passes through this delay line. The delay line is programmed in degrees of offset, so that one could think of the clock period representing 360deg of delay. In an ideal environment, delaying the strobe 1/4 of a clock cycle (90deg) would place the strobe in the middle of the data packet. This delayed strobe can then be used to clock the data into a register, satisfying setup and hold requirements of the system.
NASA Technical Reports Server (NTRS)
Ma, Y.
1995-01-01
The AMSU-A receiver subsystem comprises two separated receiver assemblies; AMSU-A1 and AMSU-A2 (P/N 1356441-1). The AMSU-A1 receiver contains 13 channels and the AMSU-A2 receiver 2 channels. The AMSU-A1 receiver assembly is further divided into two parts; AMSU-A1-1 (P/N 1356429-1) and AMSU-A1-2 (P/N 1356409-1), which contain 9 and 4 channels, respectively. The receiver assemblies are highlighted and illustrate the functional block diagrams of the AMSU-A1 and AMSU-A2 systems. The AMSU-A receiver subsystem stands in between the antenna and signal processing subsystems of the AMSU-A instrument and comprises the RF and IF components from isolators to attenuators. It receives the RF signals from the antenna subsystem, down-converts the RF signals to IF signals, amplifies and defines the IF signals to proper power level and frequency bandwidth as specified for each channel, and inputs the IF signals to the signal processing subsystem. This test report presents the test data of the EOS AMSU-A Flight Model No. 1 (FM-1) receiver subsystem. The tests are performed per the Acceptance Test Procedure for the AMSU-A Receiver Subsystem, AE-26002/6A. The functional performance tests are conducted either at the component or subsystem level. While the component-level tests are performed over the entire operating temperature range predicted by thermal analysis, the subsystem-level tests are conducted at ambient temperature only.
Low-Cutoff, High-Pass Digital Filtering of Neural Signals
NASA Technical Reports Server (NTRS)
Mojarradi,Mohammad; Johnson, Travis; Ortiz, Monico; Cunningham, Thomas; Andersen, Richard
2004-01-01
The figure depicts the major functional blocks of a system, now undergoing development, for conditioning neural signals acquired by electrodes implanted in a brain. The overall functions to be performed by this system can be summarized as preamplification, multiplexing, digitization, and high-pass filtering. Other systems under development for recording neural signals typically contain resistor-capacitor analog low-pass filters characterized by cutoff frequencies in the vicinity of 100 Hz. In the application for which this system is being developed, there is a requirement for a cutoff frequency of 5 Hz. Because the resistors needed to obtain such a low cutoff frequency would be impractically large, it was decided to perform low-pass filtering by use of digital rather than analog circuitry. In addition, it was decided to timemultiplex the digitized signals from the multiple input channels into a single stream of data in a single output channel. The signal in each input channel is first processed by a preamplifier having a voltage gain of approximately 50. Embedded in each preamplifier is a low-pass anti-aliasing filter having a cutoff frequency of approximately 10 kHz. The anti-aliasing filters make it possible to couple the outputs of the preamplifiers to the input ports of a multiplexer. The output of the multiplexer is a single stream of time-multiplexed samples of analog signals. This stream is processed by a main differential amplifier, the output of which is sent to an analog-to-digital converter (ADC). The output of the ADC is sent to a digital signal processor (DSP).
GPS Space Service Volume: Ensuring Consistent Utility Across GPS Design Builds for Space Users
NASA Technical Reports Server (NTRS)
Bauer, Frank H.; Parker, Joel Jefferson Konkl; Valdez, Jennifer Ellen
2015-01-01
GPS availability and signal strength originally specified for users on or near surface of Earth with transmitted power levels specified at edge-of-Earth, 14.3 degrees. Prior to the SSV specification, on-orbit performance of GPS varied from block build to block build (IIA, IIRM, IIF) due to antenna gain and beam width variances. Unstable on-orbit performance results in significant risk to space users. Side-lobe signals, although not specified, were expected to significantly boost GPS signal availability for users above the constellation. During GPS III Phase A, NASA noted significant discrepancies in power levels specified in GPS III specification documents, and measured on-orbit performance. To stabilize the signal for high altitude space users, NASA DoD team in 2003-2005 led the creation of new Space Service Volume (SSV) definition and specifications.
Chang, Fang-Mei; Reyna, Sara M.; Granados, Jose C.; Wei, Sung-Jen; Innis-Whitehouse, Wendy; Maffi, Shivani K.; Rodriguez, Edward; Slaga, Thomas J.; Short, John D.
2012-01-01
Cullin-RING E3 ligases (CRLs) are a class of ubiquitin ligases that control the proteasomal degradation of numerous target proteins, including IκB, and the activity of these CRLs are positively regulated by conjugation of a Nedd8 polypeptide onto Cullin proteins in a process called neddylation. CRL-mediated degradation of IκB, which normally interacts with and retains NF-κB in the cytoplasm, permits nuclear translocation and transactivation of the NF-κB transcription factor. Neddylation occurs through a multistep enzymatic process involving Nedd8 activating enzymes, and recent studies have shown that the pharmacological agent, MLN4924, can potently inhibit Nedd8 activating enzymes, thereby preventing neddylation of Cullin proteins and preventing the degradation of CRL target proteins. In macrophages, regulation of NF-κB signaling functions as a primary pathway by which infectious agents such as lipopolysaccharides (LPSs) cause the up-regulation of proinflammatory cytokines. Here we have analyzed the effects of MLN4924, and compared the effects of MLN4924 with a known anti-inflammatory agent (dexamethasone), on certain proinflammatory cytokines (TNF-α and IL-6) and the NF-κB signaling pathway in LPS-stimulated macrophages. We also used siRNA to block neddylation to assess the role of this molecular process during LPS-induced cytokine responsiveness. Our results demonstrate that blocking neddylation, either pharmacologically or using siRNA, abrogates the increase in certain proinflammatory cytokines secreted from macrophages in response to LPS. In addition, we have shown that MLN4924 and dexamethasone inhibit LPS-induced cytokine up-regulation at the transcriptional level, albeit through different molecular mechanisms. Thus, neddylation represents a novel molecular process in macrophages that can be targeted to prevent and/or treat the LPS-induced up-regulation of proinflammatory cytokines and the disease processes associated with their up-regulation. PMID:22927439
Salicylic acid signaling inhibits apoplastic reactive oxygen species signaling
2014-01-01
Background Reactive oxygen species (ROS) are used by plants as signaling molecules during stress and development. Given the amount of possible challenges a plant face from their environment, plants need to activate and prioritize between potentially conflicting defense signaling pathways. Until recently, most studies on signal interactions have focused on phytohormone interaction, such as the antagonistic relationship between salicylic acid (SA)-jasmonic acid and cytokinin-auxin. Results In this study, we report an antagonistic interaction between SA signaling and apoplastic ROS signaling. Treatment with ozone (O3) leads to a ROS burst in the apoplast and induces extensive changes in gene expression and elevation of defense hormones. However, Arabidopsis thaliana dnd1 (defense no death1) exhibited an attenuated response to O3. In addition, the dnd1 mutant displayed constitutive expression of defense genes and spontaneous cell death. To determine the exact process which blocks the apoplastic ROS signaling, double and triple mutants involved in various signaling pathway were generated in dnd1 background. Simultaneous elimination of SA-dependent and SA-independent signaling components from dnd1 restored its responsiveness to O3. Conversely, pre-treatment of plants with SA or using mutants that constitutively activate SA signaling led to an attenuation of changes in gene expression elicited by O3. Conclusions Based upon these findings, we conclude that plants are able to prioritize the response between ROS and SA via an antagonistic action of SA and SA signaling on apoplastic ROS signaling. PMID:24898702
Salicylic acid signaling inhibits apoplastic reactive oxygen species signaling.
Xu, Enjun; Brosché, Mikael
2014-06-04
Reactive oxygen species (ROS) are used by plants as signaling molecules during stress and development. Given the amount of possible challenges a plant face from their environment, plants need to activate and prioritize between potentially conflicting defense signaling pathways. Until recently, most studies on signal interactions have focused on phytohormone interaction, such as the antagonistic relationship between salicylic acid (SA)-jasmonic acid and cytokinin-auxin. In this study, we report an antagonistic interaction between SA signaling and apoplastic ROS signaling. Treatment with ozone (O3) leads to a ROS burst in the apoplast and induces extensive changes in gene expression and elevation of defense hormones. However, Arabidopsis thaliana dnd1 (defense no death1) exhibited an attenuated response to O3. In addition, the dnd1 mutant displayed constitutive expression of defense genes and spontaneous cell death. To determine the exact process which blocks the apoplastic ROS signaling, double and triple mutants involved in various signaling pathway were generated in dnd1 background. Simultaneous elimination of SA-dependent and SA-independent signaling components from dnd1 restored its responsiveness to O3. Conversely, pre-treatment of plants with SA or using mutants that constitutively activate SA signaling led to an attenuation of changes in gene expression elicited by O3. Based upon these findings, we conclude that plants are able to prioritize the response between ROS and SA via an antagonistic action of SA and SA signaling on apoplastic ROS signaling.
Carmenate, Tania; Ortíz, Yaquelín; Enamorado, Michel; García-Martínez, Karina; Avellanet, Janet; Moreno, Ernesto; Graça, Luis; León, Kalet
2018-05-15
IL-2 is critical for peripheral tolerance mediated by regulatory T (Treg) cells, which represent an obstacle for effective cancer immunotherapy. Although IL-2 is important for effector (E) T cell function, it has been hypothesized that therapies blocking IL-2 signals weaken Treg cell activity, promoting immune responses. This hypothesis has been partially tested using anti-IL-2 or anti-IL-2R Abs with antitumor effects that cannot be exclusively attributed to lack of IL-2 signaling in vivo. In this work, we pursued an alternative strategy to block IL-2 signaling in vivo, taking advantage of the trimeric structure of the IL-2R. We designed an IL-2 mutant that conserves the capacity to bind to the αβ-chains of the IL-2R but not to the γ c -chain, thus having a reduced signaling capacity. We show our IL-2 mutein inhibits IL-2 Treg cell-dependent differentiation and expansion. Moreover, treatment with IL-2 mutein reduces Treg cell numbers and impairs tumor growth in mice. A mathematical model was used to better understand the effect of the mutein on Treg and E T cells, suggesting suitable strategies to improve its design. Our results show that it is enough to transiently inhibit IL-2 signaling to bias E and Treg cell balance in vivo toward immunity. Copyright © 2018 by The American Association of Immunologists, Inc.
Cocaine Modulates Mammalian Circadian Clock Timing by Decreasing Serotonin Transport in the SCN
Prosser, Rebecca A.; Stowie, Adam; Amicarelli, Mario; Nackenoff, Alex G.; Blakely, Randy D.; Glass, J. David
2014-01-01
Cocaine abuse disrupts reward and homeostatic processes through diverse processes, including those involved in circadian clock regulation. Recently we showed that cocaine administration to mice disrupts nocturnal photic phase resetting of the suprachiasmatic (SCN) circadian clock, whereas administration during the day induces non-photic phase shifts. Importantly, the same effects are seen when cocaine is applied to the SCN in vitro, where it blocks photic-like (glutamate-induced) phase shifts at night and induces phase advances during the day. Furthermore, our previous data suggest that cocaine acts in the SCN by enhancing serotonin (5-HT) signaling. For example, the in vitro actions of cocaine mimic those of 5-HT and are blocked by the 5-HT antagonist, metergoline, but not the dopamine receptor antagonist, fluphenazine. Although our data are consistent with cocaine acting through enhance 5-HT signaling, the nonselective actions of cocaine as an antagonist of monoamine transporters raises the question of whether inhibition of the 5-HT transporter (SERT) is key to its circadian effects. Here we investigate this issue using transgenic mice expressing a SERT that exhibits normal 5-HT recognition and transport but significantly reduced cocaine potency (SERT Met172). Circadian patterns of SCN behavioral and neuronal activity did not differ between WT and SERT Met172 mice, nor did they differ in the ability of the 5-HT1A,2,7 receptor agonist, 8-OH-DPAT to reset SCN clock phase, consistent with the normal SERT expression and activity in the transgenic mice. However, 1) cocaine administration does not induce phase advances when administered in vivo or in vitro in SERT Met172 mice; 2) cocaine does not block photic or glutamate-induced (phase shifts in SERT Met172 mice; and 3) cocaine does not induce long-term changes in free-running period in SERT Met172 mice. We conclude that SERT antagonism is required for the phase shifting of the SCN circadian clock induced by cocaine. PMID:24950119
NASA Astrophysics Data System (ADS)
Siddiqui, Aleem; Reinke, Charles; Shin, Heedeuk; Jarecki, Robert L.; Starbuck, Andrew L.; Rakich, Peter
2017-05-01
The performance of electronic systems for radio-frequency (RF) spectrum analysis is critical for agile radar and communications systems, ISR (intelligence, surveillance, and reconnaissance) operations in challenging electromagnetic (EM) environments, and EM-environment situational awareness. While considerable progress has been made in size, weight, and power (SWaP) and performance metrics in conventional RF technology platforms, fundamental limits make continued improvements increasingly difficult. Alternatively, we propose employing cascaded transduction processes in a chip-scale nano-optomechanical system (NOMS) to achieve a spectral sensor with exceptional signal-linearity, high dynamic range, narrow spectral resolution and ultra-fast sweep times. By leveraging the optimal capabilities of photons and phonons, the system we pursue in this work has performance metrics scalable well beyond the fundamental limitations inherent to all electronic systems. In our device architecture, information processing is performed on wide-bandwidth RF-modulated optical signals by photon-mediated phononic transduction of the modulation to the acoustical-domain for narrow-band filtering, and then back to the optical-domain by phonon-mediated phase modulation (the reverse process). Here, we rely on photonics to efficiently distribute signals for parallel processing, and on phononics for effective and flexible RF-frequency manipulation. This technology is used to create RF-filters that are insensitive to the optical wavelength, with wide center frequency bandwidth selectivity (1-100GHz), ultra-narrow filter bandwidth (1-100MHz), and high dynamic range (70dB), which we will present. Additionally, using this filter as a building block, we will discuss current results and progress toward demonstrating a multichannel-filter with a bandwidth of < 10MHz per channel, while minimizing cumulative optical/acoustic/optical transduced insertion-loss to ideally < 10dB. These proposed metric represent significant improvements over RF-platforms.
Detection of Tampering Inconsistencies on Mobile Photos
NASA Astrophysics Data System (ADS)
Cao, Hong; Kot, Alex C.
Fast proliferation of mobile cameras and the deteriorating trust on digital images have created needs in determining the integrity of photos captured by mobile devices. As tampering often creates some inconsistencies, we propose in this paper a novel framework to statistically detect the image tampering inconsistency using accurately detected demosaicing weights features. By first cropping four non-overlapping blocks, each from one of the four quadrants in the mobile photo, we extract a set of demosaicing weights features from each block based on a partial derivative correlation model. Through regularizing the eigenspectrum of the within-photo covariance matrix and performing eigenfeature transformation, we further derive a compact set of eigen demosaicing weights features, which are sensitive to image signal mixing from different photo sources. A metric is then proposed to quantify the inconsistency based on the eigen weights features among the blocks cropped from different regions of the mobile photo. Through comparison, we show our eigen weights features perform better than the eigen features extracted from several other conventional sets of statistical forensics features in detecting the presence of tampering. Experimentally, our method shows a good confidence in tampering detection especially when one of the four cropped blocks is from a different camera model or brand with different demosaicing process.
Characterization of blocks impacts from acoustic emissions: insights from laboratory experiments
NASA Astrophysics Data System (ADS)
Farin, Maxime; Mangeney, Anne; de Rosny, Julien; Toussaint, Renaud; Shapiro, Nikolaï
2014-05-01
Rockfalls, debris flows and rock avalanches represent a major natural hazard for the population in mountainous, volcanic and coastal areas but their direct observation on the field is very dangerous. Recent studies showed that gravitational instabilities can be detected and characterized (volume, duration,...) thanks to the seismic signal they generate. In an avalanche, individual block bouncing and rolling on the ground are expected to generated signals of higher frequencies than the main flow spreading. The identification of the time/frequency signature of individual blocks in the recorded signal remains however difficult. Laboratory experiments were conducted to investigate the acoustic signature of diverse simple sources corresponding to grains falling over thin plates of plexiglas and glass and over rock blocks. The elastic energy emitted by a single bouncing bead into the support was first quantitatively estimated and compared to the potential energy of fall and to the potential energy change during the shock. We obtained simple scaling laws relating the impactor characteristics (size, height of fall, material,...) to the elastic energy and spectral content. Next, we consider the collapse of granular columns made of steel spherical beads onto hard substrates. Initially, these columns were held by a magnetic field allowing to suppress suddenly the cohesion between the beads, and thus to minimize friction effects that would arise from side walls. We varied systematically the column volume, the column aspect ratio (height over length) and the grain size. This is shown to affect the signal envelope and frequency content. In the experiments, accelerometers (1 Hz to 56 kHz) were used to record the signals in a wide frequency range. The experiments were also monitored optically using fast cameras. Eventually, we looked at what types of features in the signal are affected by individual impacts, rolling of beads or by the large scale geometry of the avalanche.
Characterization of blocks impacts from elastic waves: insights from laboratory experiments
NASA Astrophysics Data System (ADS)
Farin, M.; Mangeney, A.; Toussaint, R.; De Rosny, J.; Shapiro, N.
2013-12-01
Rockfalls, debris flows and rock avalanches constitute a major natural hazard for the population in mountainous, volcanic and coastal areas but their direct observation on the field is very dangerous. Recent studies showed that gravitational instabilities can be detected and characterized (volume, duration,...) thanks to the seismic signal they generate. In an avalanche, individual block bouncing and rolling on the ground are expected to generated signals of higher frequencies than the main flow spreading. The identification of the time/frequency signature of individual blocks in the recorded signal remains however difficult. Laboratory experiments were conducted to investigate the acoustic signature of diverse simple sources corresponding to grains falling over thin plates of plexiglas and rock blocks. The elastic energy emitted by a single bouncing steel bead into the support was first quantitatively estimated and compared to the potential energy of fall and to the potential energy change during the shock. Next, we consider the collapse of granular columns made of steel spherical beads onto hard substrates. Initially, these columns were held by a magnetic field allowing to suppress suddenly the cohesion between the beads, and thus to minimize friction effects that would arise from side walls. We varied systematically the column volume, the column aspect ratio (height over length) and the grain size. This is shown to affect the signal envelope and frequency content. In the experiments, two types of acoustic sensors were used to record the signals in a wide frequency range: accelerometers (1 Hz to 56 kHz) and piezoelectric sensors (100 kHz to 1 MHz). The experiments were also monitored optically using fast cameras. We developed a technique to use quantitatively both types of sensors to evaluate the elastic energy emitted by the sources. Eventually, we looked at what types of features in the signal are affected by individual shocks or by the large scale geometry of the avalanche.
Role of nitric oxide in pheromone-mediated intraspecific communication in mice.
Agustín-Pavón, Carmen; Martínez-Ricós, Joana; Martínez-García, Fernando; Lanuza, Enrique
2009-12-07
Nitric oxide is known to take part in the control of sexual and agonistic behaviours. This is usually attributed to its role in neural transmission in the hypothalamus and other structures of the limbic system. However, socio-sexual behaviours in rodents are mainly directed by chemical signals detected by the vomeronasal system, and nitric oxide is abundant in key structures along the vomeronasal pathway. Thus, here we check whether pharmacological treatments interfering with nitrergic transmission could affect socio-sexual behaviour by impairing the processing of chemical signals. Treatment with an inhibitor of nitric oxide synthesis (Nomega-Nitro-l-arginine methyl ester hydrochloride, L-NAME, 100mg/kg) blocks the innate preference displayed by female mice for sexual pheromones contained in male-soiled bedding, with a lower dose of the drug (50mg/kg) having no effect. Animals treated with the high dose of L-NAME show no reduction of olfactory discrimination of male urine in a habituation-dishabituation test, thus suggesting that the effect of the drug on the preference for male pheromones is not due to an inability to detect male urine. Alternatively, it may result from an alteration in processing the reinforcing value of pheromones as sexual signals. These results add a new piece of evidence to our understanding of the neurochemistry of intraspecific chemical communication in rodents, and suggest that the role of nitric oxide in socio-sexual behaviours should be re-evaluated taking into account the involvement of this neuromodulator in the processing of chemical signals.
Yoshida, Eiji; Tashima, Hideaki; Inadama, Naoko; Nishikido, Fumihiko; Moriya, Takahiro; Omura, Tomohide; Watanabe, Mitsuo; Murayama, Hideo; Yamaya, Taiga
2013-01-01
The X'tal cube is a depth-of-interaction (DOI)-PET detector which is aimed at obtaining isotropic resolution by effective readout of scintillation photons from the six sides of a crystal block. The X'tal cube is composed of the 3D crystal block with isotropic resolution and arrays of multi-pixel photon counters (MPPCs). In this study, to fabricate the 3D crystal block efficiently and precisely, we applied a sub-surface laser engraving (SSLE) technique to a monolithic crystal block instead of gluing segmented small crystals. The SSLE technique provided micro-crack walls which carve a groove into a monolithic scintillator block. Using the fabricated X'tal cube, we evaluated its intrinsic spatial resolution to show a proof of concept of isotropic resolution. The 3D grids of 2 mm pitch were fabricated into an 18 × 18 × 18 mm(3) monolithic lutetium yttrium orthosilicate (LYSO) crystal by the SSLE technique. 4 × 4 MPPCs were optically coupled to each surface of the crystal block. The X'tal cube was uniformly irradiated by (22)Na gamma rays, and all of the 3D grids on the 3D position histogram were separated clearly by an Anger-type calculation from the 96-channel MPPC signals. Response functions of the X'tal cube were measured by scanning with a (22)Na point source. The gamma-ray beam with a 1.0 mm slit was scanned in 0.25 mm steps by positioning of the X'tal cube at vertical and 45° incident angles. The average FWHM resolution at both incident angles was 2.1 mm. Therefore, we confirmed the isotropic spatial resolution performance of the X'tal cube.
Lintas, Alessandra; Chi, Ning; Lauzon, Nicole M; Bishop, Stephanie F; Gholizadeh, Shervin; Sun, Ninglei; Tan, Huibing; Laviolette, Steven R
2011-08-03
The basolateral amygdala (BLA), ventral tegmental area (VTA), and nucleus accumbens (NAc) play central roles in the processing of opiate-related associative reward learning and memory. The BLA receives innervation from dopaminergic fibers originating in the VTA, and both dopamine (DA) D1 and D2 receptors are expressed in this region. Using a combination of in vivo single-unit extracellular recording in the NAc combined with behavioral pharmacology studies, we have identified a double dissociation in the functional roles of DA D1 versus D2 receptor transmission in the BLA, which depends on opiate exposure state; thus, in previously opiate-naive rats, blockade of intra-BLA D1, but not D2, receptor transmission blocked the acquisition of associative opiate reward memory, measured in an unbiased conditioned place preference procedure. In direct contrast, in rats made opiate dependent and conditioned in a state of withdrawal, intra-BLA D2, but not D1, receptor blockade blocked opiate reward encoding. This functional switch was dependent on cAMP signaling as comodulation of intra-BLA cAMP levels reversed or replicated the functional effects of intra-BLA D1 or D2 transmission during opiate reward processing. Single-unit in vivo extracellular recordings performed in neurons of the NAc confirmed an opiate-state-dependent role for BLA D1/D2 transmission in NAc neuronal response patterns to morphine. Our results characterize and identify a novel opiate addiction switching mechanism directly in the BLA that can control the processing of opiate reward information as a direct function of opiate exposure state via D1 or D2 receptor signaling substrates.
Liu, Danya; Badell, I. Raul; Ford, Mandy L.
2018-01-01
Memory T cells pose a significant problem to successful therapeutic control of unwanted immune responses during autoimmunity and transplantation, as they are differentially controlled by cosignaling receptors such as CD28 and CTLA-4. Treatment with abatacept and belatacept impede CD28 signaling by binding to CD80 and CD86, but they also have the unintended consequence of blocking the ligands for CTLA-4, a process that may inadvertently boost effector responses. Here, we show that a potentially novel anti-CD28 domain antibody (dAb) that selectively blocks CD28 but preserves CTLA-4 coinhibition confers improved allograft survival in sensitized recipients as compared with CTLA-4 Ig. However, both CTLA-4 Ig and anti-CD28 dAb similarly and significantly reduced the accumulation of donor-reactive CD8+ memory T cells, demonstrating that regulation of the expansion of CD8+ memory T cell populations is controlled in part by CD28 signals and is not significantly impacted by CTLA-4. In contrast, selective CD28 blockade was superior to CTLA-4 Ig in inhibiting IFN-γ, TNF, and IL-2 production by CD8+ memory T cells, which in turn resulted in reduced recruitment of innate CD11b+ monocytes into allografts. Importantly, this superiority was CTLA-4 dependent, demonstrating that effector function of CD8+ memory T cells is regulated by the balance of CD28 and CTLA-4 signaling. PMID:29321374
Redondo-Muñoz, Javier; José Terol, María; García-Marco, José A; García-Pardo, Angeles
2008-01-01
B-cell chronic lymphocytic leukemia (B-CLL) progression is frequently accompanied by clinical lymphadenopathy, and the CCL21 chemokine may play an important role in this process. Indeed, CCR7 (the CCL21 receptor), as well as matrix metalloproteinase-9 (MMP-9), are overexpressed in infiltrating B-CLL cells. We have studied whether MMP-9 is regulated by CCL21 and participates in CCL21-dependent migration. CCL21 significantly increased B-CLL MMP-9 production, measured by gelatin zymography. This was inhibited by blocking extracellular signal-regulated kinase-1/2 (ERK1/2) activity or by cell transfection with CCR7-siRNA. Accordingly, CCL21/CCR7 interaction activated the ERK1/2/c-Fos pathway and increased MMP-9 mRNA. CCL21-driven B-CLL cell migration through Matrigel or human umbilical vein endothelial cells (HUVEC) was blocked by anti-CCR7 antibodies, CCR7-siRNA transfection, or the ERK1/2 inhibitor U0126, as well as by anti-MMP-9 antibodies or tissue inhibitor of metalloproteinase 1 (TIMP-1). These results strongly suggest that MMP-9 is involved in B-CLL nodal infiltration and expand the roles of MMP-9 and CCR7 in B-CLL progression. Both molecules could thus constitute therapeutic targets for this disease.
Zumer, Johanna M.; Scheeringa, René; Schoffelen, Jan-Mathijs; Norris, David G.; Jensen, Ole
2014-01-01
Given the limited processing capabilities of the sensory system, it is essential that attended information is gated to downstream areas, whereas unattended information is blocked. While it has been proposed that alpha band (8–13 Hz) activity serves to route information to downstream regions by inhibiting neuronal processing in task-irrelevant regions, this hypothesis remains untested. Here we investigate how neuronal oscillations detected by electroencephalography in visual areas during working memory encoding serve to gate information reflected in the simultaneously recorded blood-oxygenation-level-dependent (BOLD) signals recorded by functional magnetic resonance imaging in downstream ventral regions. We used a paradigm in which 16 participants were presented with faces and landscapes in the right and left hemifields; one hemifield was attended and the other unattended. We observed that decreased alpha power contralateral to the attended object predicted the BOLD signal representing the attended object in ventral object-selective regions. Furthermore, increased alpha power ipsilateral to the attended object predicted a decrease in the BOLD signal representing the unattended object. We also found that the BOLD signal in the dorsal attention network inversely correlated with visual alpha power. This is the first demonstration, to our knowledge, that oscillations in the alpha band are implicated in the gating of information from the visual cortex to the ventral stream, as reflected in the representationally specific BOLD signal. This link of sensory alpha to downstream activity provides a neurophysiological substrate for the mechanism of selective attention during stimulus processing, which not only boosts the attended information but also suppresses distraction. Although previous studies have shown a relation between the BOLD signal from the dorsal attention network and the alpha band at rest, we demonstrate such a relation during a visuospatial task, indicating that the dorsal attention network exercises top-down control of visual alpha activity. PMID:25333286
Influence of Solar Variability on the North Atlantic / European Sector.
NASA Astrophysics Data System (ADS)
Gray, L. J.
2016-12-01
The 11year solar cycle signal in December-January-February averaged mean-sea-level pressure and Atlantic/European blocking frequency is examined using multilinear regression with indices to represent variability associated with the solar cycle, volcanic eruptions, the El Nino - Southern Oscillation (ENSO) and the Atlantic Multidecadal Oscillation (AMO). Results from a previous 11-year solar cycle signal study of the period 1870-2010 (140 years; 13 solar cycles) that suggested a 3-4 year lagged signal in SLP over the Atlantic are confirmed by analysis of a much longer reconstructed dataset for the period 1660-2010 (350 years; 32 solar cycles). Apparent discrepancies between earlier studies are resolved and stem primarily from the lagged nature of the response and differences between early- and late-winter responses. Analysis of the separate winter months provide supporting evidence for two mechanisms of influence, one operating via the atmosphere that maximises in late winter at 0-2 year lags and one via the mixd-layer ocean that maximises in early winter at 3-4 year lags. Corresponding analysis of DJF-averaged Atlantic / European blocking frequency shows a highly statistically significant signal at 1-year lag that originates promarily from the late winter response. The 11-year solar signal in DJF blocking frequency is compared with other known influences from ENSO and the AMO and found to be as large in amplitude and have a larger region of statistical significance.
She, Linlin; Xu, Dan; Wang, Zixia; Zhang, Yirui; Wei, Qingli; Aa, Jiye; Wang, Guangji; Liu, Baolin; Xie, Yuan
2018-05-07
Aberrant succinate accumulation emerges as a unifying mechanism for inflammation and oxidative stress. This study aims to investigate whether curcumin ameliorates hepatic fibrosis via blocking succinate signaling. We investigated the effects of curcumin on hepatic succinate accumulation and liver fibrosis in mice fed a high-fat diet (HFD). Meanwhile, we stimulated mouse primary hepatic stellate cells (HSCs) with succinate and observed the inhibitory effects of curcumin on succinate signaling. Oral administration of curcumin and metformin combated mitochondrial fatty acid oxidation and reduced hepatic succinate accumulation due to the inhibition of succinate dehydrogenase (SDH) activity and demonstrated inhibitory effect on hepatic fibrosis. In mouse primary HSCs, curcumin prevented succinate- and CoCl 2 -induced hypoxia-inducible transcription factor-1α (HIF-1α) induction via suppression of ROS production and effectively reduced gene expressions of Col1α, Col3α, fibronectin and TGF-β1 with inflammation inhibition. Knockdown of HIF-1α with small interfering RNA blocked the action of succinate to induce HSCs activation, indicative of the essential role of HIF-1α in succinate signaling. Hepatic succinate accumulation served as a metabolic signal to promote liver fibrosis through HIF-1α induction. Curcumin reduced succinate accumulation by combating fatty acid oxidation and prevented HSCs activation by blocking succinate/HIF-1α signaling pathway. Copyright © 2018. Published by Elsevier B.V.
Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling
Tal, Michal Caspi; Sasai, Miwa; Lee, Heung Kyu; Yordy, Brian; Shadel, Gerald S.; Iwasaki, Akiko
2009-01-01
Autophagy is a highly conserved process that maintains homeostasis by clearing damaged organelles and long-lived proteins. The consequences of deficiency in autophagy manifest in a variety of pathological states including neurodegenerative diseases, inflammatory disorders, and cancer. Here, we studied the role of autophagy in the homeostatic regulation of innate antiviral defense. Single-stranded RNA viruses are recognized by the members of the RIG-I-like receptors (RLRs) in the cytosol. RLRs signal through IPS-1, resulting in the production of the key antiviral cytokines, type I IFNs. Autophagy-defective Atg5−/− cells exhibited enhanced RLR signaling, increased IFN secretion, and resistance to infection by vesicular stomatitis virus. In the absence of autophagy, cells accumulated dysfunctional mitochondria, as well as mitochondria-associated IPS-1. Reactive oxygen species (ROS) associated with the dysfunctional mitochondria were largely responsible for the enhanced RLR signaling in Atg5−/− cells, as antioxidant treatment blocked the excess RLR signaling. In addition, autophagy-independent increase in mitochondrial ROS by treatment of cells with rotenone was sufficient to amplify RLR signaling in WT cells. These data indicate that autophagy contributes to homeostatic regulation of innate antiviral defense through the clearance of dysfunctional mitochondria, and revealed that ROS associated with mitochondria play a key role in potentiating RLR signaling. PMID:19196953
Role of the FGF and MEK signaling pathway in the ascidian embryo.
Kim, G J; Nishida, H
2001-10-01
In the ascidian embryo, a fibroblast growth factor (FGF)-like signal from presumptive endoderm blastomeres between the 32-cell and early 64-cell stages induces the formation of notochord and mesenchyme cells. However, it has not been known whether endogenous FGF signaling is involved in the process. Here it is shown that 64-cell embryos exhibit a marked increase in endogenous extracellular signal-regulated kinase (ERK/MAPK) activity. The increase in ERK activity was reduced by treatment with an FGF receptor 1 inhibitor, SU5402, and a MEK (ERK kinase/MAPKK) inhibitor, U0126. Both drugs blocked the formation of notochord and mesenchyme when embryos were treated at the 32-cell stage, but not at the 2- or 110-cell stages. The dominant-negative form of Ras also suppressed notochord and mesenchyme formation. Both inhibitors suppressed induction by exogenous basic FGF. These results suggest that the FGF signaling cascade is indeed necessary for the formation of notochord and mesenchyme cells during ascidian embryogenesis. It is also shown that FGF signaling is required for formation of the secondary notochord, secondary muscle and neural tissues, and at least ERK activity is necessary for the formation of trunk lateral cells and posterior endoderm. Therefore, FGF and MEK signaling are required for the formation of various tissues in the ascidian embryo.
Mizunami, Makoto; Matsumoto, Yukihisa
2017-01-01
Revealing neural systems that mediate appetite and aversive signals in associative learning is critical for understanding the brain mechanisms controlling adaptive behavior in animals. In mammals, it has been shown that some classes of dopamine neurons in the midbrain mediate prediction error signals that govern the learning process, whereas other classes of dopamine neurons control execution of learned actions. In this review, based on the results of our studies on Pavlovian conditioning in the cricket Gryllus bimaculatus and by referring to the findings in honey bees and fruit-flies, we argue that comparable aminergic systems exist in the insect brain. We found that administrations of octopamine (the invertebrate counterpart of noradrenaline) and dopamine receptor antagonists impair conditioning to associate an olfactory or visual conditioned stimulus (CS) with water or sodium chloride solution (appetitive or aversive unconditioned stimulus, US), respectively, suggesting that specific octopamine and dopamine neurons mediate appetitive and aversive signals, respectively, in conditioning in crickets. These findings differ from findings in fruit-flies. In fruit-flies, appetitive and aversive signals are mediated by different dopamine neuron subsets, suggesting diversity in neurotransmitters mediating appetitive signals in insects. We also found evidences of "blocking" and "auto-blocking" phenomena, which suggested that the prediction error, the discrepancy between actual US and predicted US, governs the conditioning in crickets and that octopamine neurons mediate prediction error signals for appetitive US. Our studies also showed that activations of octopamine and dopamine neurons are needed for the execution of an appetitive conditioned response (CR) and an aversive CR, respectively, and we, thus, proposed that these neurons mediate US prediction signals that drive appetitive and aversive CRs. Our findings suggest that the basic principles of functioning of aminergic systems in associative learning, i.e., to transmit prediction error signals for conditioning and to convey US prediction signals for execution of CR, are conserved among insects and mammals, on account of the fact that the organization of the insect brain is much simpler than that of the mammalian brain. Further investigation of aminergic systems that govern associative learning in insects should lead to a better understanding of commonalities and diversities of computational rules underlying associative learning in animals.
Optical integrator for optical dark-soliton detection and pulse shaping.
Ngo, Nam Quoc
2006-09-10
The design and analysis of an Nth-order optical integrator using the digital filter technique is presented. The optical integrator is synthesized using planar-waveguide technology. It is shown that a first-order optical integrator can be used as an optical dark-soliton detector by converting an optical dark-soliton pulse into an optical bell-shaped pulse for ease of detection. The optical integrators can generate an optical step function, staircase function, and paraboliclike functions from input optical Gaussian pulses. The optical integrators may be potentially used as basic building blocks of all-optical signal processing systems because the time integrals of signals may sometimes be required for further use or analysis. Furthermore, an optical integrator may be used for the shaping of optical pulses or in an optical feedback control system.
Advanced Receiver tracking of Voyager 2 near solar conjunction
NASA Technical Reports Server (NTRS)
Brown, D. H.; Hurd, W. J.; Vilnrotter, V. A.; Wiggins, J. D.
1988-01-01
The Advanced Receiver (ARX) was used to track the Voyager 2 spacecraft at low Sun-Earth-Probe (SEP) angles near solar conjunction in December of 1987. The received carrier signal exhibited strong fluctuations in both phase and amplitude. The ARX used spectral estimation and mathematical modeling of the phase and receiver noise processes to set an optimum carrier tracking bandwidth. This minimized the mean square phase error in tracking carrier phase and thus minimized the loss in the telemetry signal-to-noise ratio due to the carrier loop. Recovered symbol SNRs and errors in decoded engineering data for the ARX are compared with those for the current Block 3 telemetry stream. Optimum bandwidths are plotted against SEP angle. Measurements of the power spectral density of the solar phase and amplitude fluctuations are also given.
NASA's next generation all-digital deep space network breadboard receiver
NASA Technical Reports Server (NTRS)
Hinedi, Sami
1993-01-01
This paper describes the breadboard advanced receiver (ARX) that is currently being built for future use in NASA's deep space network (DSN). This receiver has unique requirements in having to operate with very weak signals from deep space probes and provide high quality telemetry and tracking data. The hybrid analog/digital receiver performs multiple functions including carrier, subcarrier and symbol synchronization. Tracking can be achieved for either residual, suppressed or hybrid carriers and for both sinusoidal and square wave subcarriers. System requirements are specified and a functional description of the ARX is presented. The various digital signal processing algorithms used are also discussed and illustrated with block diagrams. Other functions such as time tagged Doppler extraction and monitor/control are also discussed including acquisition algorithms and lock detection schemes.
Fiorucci, Sandrine; Lin, Xiaochen; Sadoul, Karin; Fournet, Guy; Bouvard, Daniel; Vinogradova, Olga; Joseph, Benoît; Block, Marc R.
2015-01-01
We previously reported the anti-migratory function of 3-aryl-2-quinolone derivatives, chemically close to flavonoids (Joseph et al., 2002). Herein we show that 3-arylquinoline or 3-aryl-2-quinolone derivatives disrupt cell adhesion in a dose dependent and reversible manner yet antagonized by artificial integrin activation such as manganese. Relying on this anti-adhesive activity, a Structure-Activity Relationship (SAR) study was established on 20 different compounds to throw the bases of future optimization strategies. Active drugs efficiently inhibit platelet spreading, aggregation, and clot retraction, processes that rely on αllbβ3 integrin activation and clustering. In vitro these derivatives interfere with β3 cytoplasmic tail interaction with kindlin-2 in pulldown assays albeit little effect was observed with pure proteins suggesting that the drugs may block an alternative integrin activation process that may not be directly related to kindlin recruitment. Ex vivo, these drugs blunt integrin signaling assayed using focal adhesion kinase auto-phosphorylation as a read-out. Hence, 3-arylquinoline and 3-aryl-2-quinolone series are a novel class of integrin activation and signaling antagonists. PMID:26509443
Programmable rate modem utilizing digital signal processing techniques
NASA Technical Reports Server (NTRS)
Bunya, George K.; Wallace, Robert L.
1989-01-01
The engineering development study to follow was written to address the need for a Programmable Rate Digital Satellite Modem capable of supporting both burst and continuous transmission modes with either binary phase shift keying (BPSK) or quadrature phase shift keying (QPSK) modulation. The preferred implementation technique is an all digital one which utilizes as much digital signal processing (DSP) as possible. Here design tradeoffs in each portion of the modulator and demodulator subsystem are outlined, and viable circuit approaches which are easily repeatable, have low implementation losses and have low production costs are identified. The research involved for this study was divided into nine technical papers, each addressing a significant region of concern in a variable rate modem design. Trivial portions and basic support logic designs surrounding the nine major modem blocks were omitted. In brief, the nine topic areas were: (1) Transmit Data Filtering; (2) Transmit Clock Generation; (3) Carrier Synthesizer; (4) Receive AGC; (5) Receive Data Filtering; (6) RF Oscillator Phase Noise; (7) Receive Carrier Selectivity; (8) Carrier Recovery; and (9) Timing Recovery.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Adams, C.; et al.
We describe the concept and procedure of drifted-charge extraction developed in the MicroBooNE experiment, a single-phase liquid argon time projection chamber (LArTPC). This technique converts the raw digitized TPC waveform to the number of ionization electrons passing through a wire plane at a given time. A robust recovery of the number of ionization electrons from both induction and collection anode wire planes will augment the 3D reconstruction, and is particularly important for tomographic reconstruction algorithms. A number of building blocks of the overall procedure are described. The performance of the signal processing is quantitatively evaluated by comparing extracted charge withmore » the true charge through a detailed TPC detector simulation taking into account position-dependent induced current inside a single wire region and across multiple wires. Some areas for further improvement of the performance of the charge extraction procedure are also discussed.« less
Complex noise suppression using a sparse representation and 3D filtering of images
NASA Astrophysics Data System (ADS)
Kravchenko, V. F.; Ponomaryov, V. I.; Pustovoit, V. I.; Palacios-Enriquez, A.
2017-08-01
A novel method for the filtering of images corrupted by complex noise composed of randomly distributed impulses and additive Gaussian noise has been substantiated for the first time. The method consists of three main stages: the detection and filtering of pixels corrupted by impulsive noise, the subsequent image processing to suppress the additive noise based on 3D filtering and a sparse representation of signals in a basis of wavelets, and the concluding image processing procedure to clean the final image of the errors emerged at the previous stages. A physical interpretation of the filtering method under complex noise conditions is given. A filtering block diagram has been developed in accordance with the novel approach. Simulations of the novel image filtering method have shown an advantage of the proposed filtering scheme in terms of generally recognized criteria, such as the structural similarity index measure and the peak signal-to-noise ratio, and when visually comparing the filtered images.
Unique membrane properties and enhanced signal processing in human neocortical neurons.
Eyal, Guy; Verhoog, Matthijs B; Testa-Silva, Guilherme; Deitcher, Yair; Lodder, Johannes C; Benavides-Piccione, Ruth; Morales, Juan; DeFelipe, Javier; de Kock, Christiaan Pj; Mansvelder, Huibert D; Segev, Idan
2016-10-06
The advanced cognitive capabilities of the human brain are often attributed to our recently evolved neocortex. However, it is not known whether the basic building blocks of the human neocortex, the pyramidal neurons, possess unique biophysical properties that might impact on cortical computations. Here we show that layer 2/3 pyramidal neurons from human temporal cortex (HL2/3 PCs) have a specific membrane capacitance ( C m ) of ~0.5 µF/cm 2 , half of the commonly accepted 'universal' value (~1 µF/cm 2 ) for biological membranes. This finding was predicted by fitting in vitro voltage transients to theoretical transients then validated by direct measurement of C m in nucleated patch experiments. Models of 3D reconstructed HL2/3 PCs demonstrated that such low C m value significantly enhances both synaptic charge-transfer from dendrites to soma and spike propagation along the axon. This is the first demonstration that human cortical neurons have distinctive membrane properties, suggesting important implications for signal processing in human neocortex.
Chirped-pulse coherent-OTDR with predistortion
NASA Astrophysics Data System (ADS)
Xiong, Ji; Jiang, Jialin; Wu, Yue; Chen, Yongxiang; Xie, Lianlian; Fu, Yun; Wang, Zinan
2018-03-01
In this paper, a novel method for generating high-quality chirped pulses with IQ modulator is studied theoretically and experimentally, which is a crucial building block for high-performance coherent optical time-domain reflectometry (COTDR). In order to compensate the nonlinearity of the modulator transfer function, we present a predistortion technique for chirped-pulse coherent optical time-domain reflectometry (CP-COTDR), the arcsin predistortion method and the single sideband with a suppressed carrier analog modulation used to generate the high quality chirped optical pulse. The high order sidebands, due to the large amplitude of the modulation signal and the nonlinear transfer function of the IQ modulator, can be relieved by the predistortion process, which means the power and the quality of the generated chirped pulse has been improved. In the experiment, this method increases the peak power of the chirped pulse by 4.2 dB compared to the case without predistortion process, as for the CP-COTDR system, this method increases the signal-to-noise ratio of the demodulated phase variation by 6.3 dB.
The Effect of Opioid Receptor Blockade on the Neural Processing of Thermal Stimuli
Schoell, Eszter D.; Bingel, Ulrike; Eippert, Falk; Yacubian, Juliana; Christiansen, Kerrin; Andresen, Hilke; May, Arne; Buechel, Christian
2010-01-01
The endogenous opioid system represents one of the principal systems in the modulation of pain. This has been demonstrated in studies of placebo analgesia and stress-induced analgesia, where anti-nociceptive activity triggered by pain itself or by cognitive states is blocked by opioid antagonists. The aim of this study was to characterize the effect of opioid receptor blockade on the physiological processing of painful thermal stimulation in the absence of cognitive manipulation. We therefore measured BOLD (blood oxygen level dependent) signal responses and intensity ratings to non-painful and painful thermal stimuli in a double-blind, cross-over design using the opioid receptor antagonist naloxone. On the behavioral level, we observed an increase in intensity ratings under naloxone due mainly to a difference in the non-painful stimuli. On the neural level, painful thermal stimulation was associated with a negative BOLD signal within the pregenual anterior cingulate cortex, and this deactivation was abolished by naloxone. PMID:20811582
Luoma, Jessie I; Stern, Christopher M; Mermelstein, Paul G.
2011-01-01
Progesterone is being utilized as a therapeutic means to ameliorate neuron loss and cognitive dysfunction following traumatic brain injury Although there have been numerous attempts to determine the means by which progesterone exerts neuroprotective effects, studies describing the underlying molecular mechanisms are lacking What has become clear, however, is the notion that progesterone can thwart several physiological processes that are detrimental to neuron function and survival, including inflammation, edema, demyelination and excitotoxicity One clue regarding the means by which progesterone has restorative value comes from the notion that these aforementioned biological processes all share the common theme of eliciting pronounced increases in intracellular calcium. Thus, we propose the hypothesis that progesterone regulation of calcium signaling underlies its ability to mitigate these cellular insults, ultimately leading to neuroprotection. Further, we describe recent findings that indicate neuroprotection is achieved via progesterone block of voltage-gated calcium channels, although additional outcomes may arise from blockade of various other ion channels and neurotransmitter receptors. PMID:22101209
Digitally Programmable Analogue Circuits for Sensor Conditioning Systems
Zatorre, Guillermo; Medrano, Nicolás; Sanz, María Teresa; Aldea, Concepción; Calvo, Belén; Celma, Santiago
2009-01-01
This work presents two current-mode integrated circuits designed for sensor signal preprocessing in embedded systems. The proposed circuits have been designed to provide good signal transfer and fulfill their function, while minimizing the load effects due to building complex conditioning architectures. The processing architecture based on the proposed building blocks can be reconfigured through digital programmability. Thus, sensor useful range can be expanded, changes in the sensor operation can be compensated for and furthermore, undesirable effects such as device mismatching and undesired physical magnitudes sensor sensibilities are reduced. The circuits were integrated using a 0.35 μm standard CMOS process. Experimental measurements, load effects and a study of two different tuning strategies are presented. From these results, system performance is tested in an application which entails extending the linear range of a magneto-resistive sensor. Circuit area, average power consumption and programmability features allow these circuits to be included in embedded sensing systems as a part of the analogue conditioning components. PMID:22412331
Gaviño, Michael A; Ford, Kevin J; Archila, Santiago; Davis, Graeme W
2015-01-01
Homeostatic signaling stabilizes synaptic transmission at the neuromuscular junction (NMJ) of Drosophila, mice, and human. It is believed that homeostatic signaling at the NMJ is bi-directional and considerable progress has been made identifying mechanisms underlying the homeostatic potentiation of neurotransmitter release. However, very little is understood mechanistically about the opposing process, homeostatic depression, and how bi-directional plasticity is achieved. Here, we show that homeostatic potentiation and depression can be simultaneously induced, demonstrating true bi-directional plasticity. Next, we show that mutations that block homeostatic potentiation do not alter homeostatic depression, demonstrating that these are genetically separable processes. Finally, we show that homeostatic depression is achieved by decreased presynaptic calcium channel abundance and calcium influx, changes that are independent of the presynaptic action potential waveform. Thus, we identify a novel mechanism of homeostatic synaptic plasticity and propose a model that can account for the observed bi-directional, homeostatic control of presynaptic neurotransmitter release. DOI: http://dx.doi.org/10.7554/eLife.05473.001 PMID:25884248
Imam, Neena; Barhen, Jacob
2009-01-01
For real-time acoustic source localization applications, one of the primary challenges is the considerable growth in computational complexity associated with the emergence of ever larger, active or passive, distributed sensor networks. These sensors rely heavily on battery-operated system components to achieve highly functional automation in signal and information processing. In order to keep communication requirements minimal, it is desirable to perform as much processing on the receiver platforms as possible. However, the complexity of the calculations needed to achieve accurate source localization increases dramatically with the size of sensor arrays, resulting in substantial growth of computational requirements that cannot bemore » readily met with standard hardware. One option to meet this challenge builds upon the emergence of digital optical-core devices. The objective of this work was to explore the implementation of key building block algorithms used in underwater source localization on the optical-core digital processing platform recently introduced by Lenslet Inc. This demonstration of considerably faster signal processing capability should be of substantial significance to the design and innovation of future generations of distributed sensor networks.« less
Multi-level bandwidth efficient block modulation codes
NASA Technical Reports Server (NTRS)
Lin, Shu
1989-01-01
The multilevel technique is investigated for combining block coding and modulation. There are four parts. In the first part, a formulation is presented for signal sets on which modulation codes are to be constructed. Distance measures on a signal set are defined and their properties are developed. In the second part, a general formulation is presented for multilevel modulation codes in terms of component codes with appropriate Euclidean distances. The distance properties, Euclidean weight distribution and linear structure of multilevel modulation codes are investigated. In the third part, several specific methods for constructing multilevel block modulation codes with interdependency among component codes are proposed. Given a multilevel block modulation code C with no interdependency among the binary component codes, the proposed methods give a multilevel block modulation code C which has the same rate as C, a minimum squared Euclidean distance not less than that of code C, a trellis diagram with the same number of states as that of C and a smaller number of nearest neighbor codewords than that of C. In the last part, error performance of block modulation codes is analyzed for an AWGN channel based on soft-decision maximum likelihood decoding. Error probabilities of some specific codes are evaluated based on their Euclidean weight distributions and simulation results.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-08-06
... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... approval for the discontinuance or modification of a signal system. FRA assigned the petition Docket Number... block signal (ABS) system on Main Line 1 and 2, from Milepost (MP) 1.2 Bliss to MP 7.3 Jay Interlocking...
Digital Construction and Characterization of Noise-like Spread Spectrum Signals
2016-11-01
Digital Construction and Characterization of Noise -like Spread Spectrum Signals Donald C. Buzanowski II, Frederick J. Block, Thomas C. Royster MIT...Lincoln Laboratory Lexington, MA 02420 Abstract—A new method for generating digital noise -like spread spectrum signals is proposed. A standard binary...employing signals that are noise -like (e.g., [1]). Direct sequence spread spectrum (DSSS) signals provide benefits such as protection against jamming, low
Howe, William M; Gritton, Howard J; Lusk, Nicholas A; Roberts, Erik A; Hetrick, Vaughn L; Berke, Joshua D; Sarter, Martin
2017-03-22
The capacity for using external cues to guide behavior ("cue detection") constitutes an essential aspect of attention and goal-directed behavior. The cortical cholinergic input system, via phasic increases in prefrontal acetylcholine release, plays an essential role in attention by mediating such cue detection. However, the relationship between cholinergic signaling during cue detection and neural activity dynamics in prefrontal networks remains unclear. Here we combined subsecond measures of cholinergic signaling, neurophysiological recordings, and cholinergic receptor blockade to delineate the cholinergic contributions to prefrontal oscillations during cue detection in rats. We first confirmed that detected cues evoke phasic acetylcholine release. These cholinergic signals were coincident with increased neuronal synchrony across several frequency bands and the emergence of theta-gamma coupling. Muscarinic and nicotinic cholinergic receptors both contributed specifically to gamma synchrony evoked by detected cues, but the effects of blocking the two receptor subtypes were dissociable. Blocking nicotinic receptors primarily attenuated high-gamma oscillations occurring during the earliest phases of the cue detection process, while muscarinic (M1) receptor activity was preferentially involved in the transition from high to low gamma power that followed and corresponded to the mobilization of networks involved in cue-guided decision making. Detected cues also promoted coupling between gamma and theta oscillations, and both nicotinic and muscarinic receptor activity contributed to this process. These results indicate that acetylcholine release coordinates neural oscillations during the process of cue detection. SIGNIFICANCE STATEMENT The capacity of learned cues to direct attention and guide responding ("cue detection") is a key component of goal-directed behavior. Rhythmic neural activity and increases in acetylcholine release in the prefrontal cortex contribute to this process; however, the relationship between these neuronal mechanisms is not well understood. Using a combination of in vivo neurochemistry, neurophysiology, and pharmacological methods, we demonstrate that cue-evoked acetylcholine release, through distinct actions at both nicotinic and muscarinic receptors, triggers a procession of neural oscillations that map onto the multiple stages of cue detection. Our data offer new insights into cholinergic function by revealing the temporally orchestrated changes in prefrontal network synchrony modulated by acetylcholine release during cue detection. Copyright © 2017 the authors 0270-6474/17/373215-16$15.00/0.
Motivational effects on the processing of delayed intentions in the anterior prefrontal cortex.
Bruening, Jovita; Ludwig, Vera U; Paschke, Lena M; Walter, Henrik; Stelzel, Christine
2018-05-15
Delaying intentions bears the risk of interference from distracting activities during the delay interval. Motivation can increase intention retrieval success but little is known about the underlying brain mechanisms. Here, we investigated whether motivational incentives (monetary reward) modulate the processing of delayed intentions in the anterior prefrontal cortex (aPFC), known to be crucial for intention processing. Using a mixed blocked and event-related functional Magnetic Resonance Imaging design, we specifically tested whether reward affects intention processing in the aPFC in a transient or in a sustained manner and whether this is related to individual differences in retrieval success. We found a generalized effect of reward on both correct intention retrieval and ongoing task performance. Fronto-parietal regions including bilateral lateral aPFC showed sustained activity increases in rewarded compared to non-rewarded blocks as well as transient reward-related activity during the storage phase. Additionally, individual differences in reward-related performance benefits were related to the degree of transient signal increases in right lateral aPFC, specifically during intention encoding. This suggests that the ability to integrate motivational relevance into the encoding of future intentions is crucial for successful intention retrieval in addition to general increases in processing effort. Bilateral aPFC is central to these motivation-cognition interactions. Copyright © 2018 Elsevier Inc. All rights reserved.
Induction of neurite extension and survival in pheochromocytoma cells by the Rit GTPase.
Spencer, Michael L; Shao, Haipeng; Andres, Douglas A
2002-06-07
The Rit, Rin, and Ric proteins comprise a distinct and evolutionarily conserved subfamily of the Ras-like small G-proteins. Although these proteins share the majority of core effector domain residues with Ras, recent studies suggest that Rit uses novel effector pathways to regulate NIH3T3 cell proliferation and transformation, while the functions of Rin and Ric remain largely unknown. Since we demonstrate that Rit is expressed in neurons, we investigated the role of Rit signaling in promoting the differentiation and survival of pheochromocytoma cells. In this study, we show that expression of constitutively active Rit (RitL79) in PC6 cells results in neuronal differentiation, characterized by the elaboration of an extensive network of neurite-like processes that are morphologically distinct from those mediated by the expression of oncogenic Ras. Although activated Rit fails to stimulate mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) signaling pathways in COS cells, RitL79 induced the phosphorylation of ERK1/2 in PC6 cells. We also find that Rit-mediated effects on neurite outgrowth can be blocked by co-expression of dominant-negative mutants of C-Raf1 or mitogen-activated protein kinase kinase 1 (MEK1). Moreover, expression of dominant-negative Rit is sufficient to inhibit NGF-induced neurite outgrowth. Expression of active Rit inhibits growth factor-withdrawal mediated apoptosis of PC6 cells, but does not induce phosphorylation of Akt/protein kinase B, suggesting that survival does not utilize the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Instead, pharmacological inhibitors of MEK block Rit-stimulated cell survival. Taken together, these studies suggest that Rit represents a distinct regulatory protein, capable of mediating differentiation and cell survival in PC6 cells using a MEK-dependent signaling pathway to achieve its effects.
Effect of Interlukin-1β on proliferation of gastric epithelial cells in culture
Beales, Ian LP
2002-01-01
Background Helicobacter pylori is the main risk factor for the development of non-cardia gastric cancer. Increased proliferation of the gastric mucosa is a feature of H. pylori infection. Mucosal interkeukin-1β production is increased in H. pylori infection and IL-1β genotypes associated with increased pro-inflammatory activity are risk factors for the development of gastric cancer. The effect of IL-1β on gastric epithelial cell proliferation has been examined in this study. Methods AGS cells were cultured with IL-1β. DNA synthesis was assed by [3H]thymidine incorporation and total viable cell numbers by MTT assay. Results IL-1β dose dependently increased DNA synthesis and cell numbers. The enhanced proliferation was blocked by interleukin-1 receptor antagonist. Addition of neutralising antibody to GM-CSF reduced IL-1β-stimulated proliferation by 31 ± 4 %. GM-CSF alone significantly stimulated proliferation. Addition or neutralisation of IL-8 had no effect on basal or IL-1β-stimulated proliferation. The tyrosine kinase inhibitor genistein completely blocked IL-1β-stimulated proliferation and inhibition of the extracellular signal related kinase pathway with PD 98059 inhibited IL-1β stimulated proliferation by 58 ± 5 %. Conclusions IL-1β stimulates proliferation in gastric epithelial cells. Autocrine stimulation by GM-CSF contributes to this proliferative response. Signalling via tyrosine kinase activity is essential to the mitogenic response to IL-1β. The extracellular signal related kinase pathway is involved in, but not essential to downstream signalling. IL-1β may contribute to the hyperproliferation seen in H. pylori- infected gastric mucosa, and be involved in the carcinogenic process. PMID:11936957
MacNeilage, Paul R.; Turner, Amanda H.
2010-01-01
Gravitational signals arising from the otolith organs and vertical plane rotational signals arising from the semicircular canals interact extensively for accurate estimation of tilt and inertial acceleration. Here we used a classical signal detection paradigm to examine perceptual interactions between otolith and horizontal semicircular canal signals during simultaneous rotation and translation on a curved path. In a rotation detection experiment, blindfolded subjects were asked to detect the presence of angular motion in blocks where half of the trials were pure nasooccipital translation and half were simultaneous translation and yaw rotation (curved-path motion). In separate, translation detection experiments, subjects were also asked to detect either the presence or the absence of nasooccipital linear motion in blocks, in which half of the trials were pure yaw rotation and half were curved path. Rotation thresholds increased slightly, but not significantly, with concurrent linear velocity magnitude. Yaw rotation detection threshold, averaged across all conditions, was 1.45 ± 0.81°/s (3.49 ± 1.95°/s2). Translation thresholds, on the other hand, increased significantly with increasing magnitude of concurrent angular velocity. Absolute nasooccipital translation detection threshold, averaged across all conditions, was 2.93 ± 2.10 cm/s (7.07 ± 5.05 cm/s2). These findings suggest that conscious perception might not have independent access to separate estimates of linear and angular movement parameters during curved-path motion. Estimates of linear (and perhaps angular) components might instead rely on integrated information from canals and otoliths. Such interaction may underlie previously reported perceptual errors during curved-path motion and may originate from mechanisms that are specialized for tilt-translation processing during vertical plane rotation. PMID:20554843
Dey, Julien H; Bianchi, Fabrizio; Voshol, Johannes; Bonenfant, Debora; Oakeley, Edward J; Hynes, Nancy E
2010-05-15
Members of the fibroblast growth factor receptor (FGFR) family have essential roles in normal physiology and in cancer where they control diverse processes. FGFRs have been associated with breast cancer development. Thus, models to study the role of FGFR in breast cancer and their targeting potential are important. We present an in vitro and in vivo analysis of FGFRs in the breast cancer model cell lines 67NR and 4T1. We show that both tumor cell lines coexpress FGFRs and ligands and display autocrine FGFR signaling activity. Fibroblast growth factor receptor substrate 2 (FRS2), a downstream mediator of FGFR, is constitutively tyrosine phosphorylated and multiple signaling pathways are active. Treatment of 67NR and 4T1 cultures with TKI258, an FGFR tyrosine kinase inhibitor (TKI), caused a rapid decrease in FRS2 phosphorylation; decreased the activity of extracellular signal-regulated kinase 1/2 (ERK1/2), AKT, and phospholipase Cgamma; and blocked proliferation of both tumor lines. Furthermore, TKI258 induced 4T1 apoptotic cell death via blockade of the phosphoinositide 3-kinase/AKT pathway. In vivo, one dose of TKI258 rapidly lowered FRS2 phosphorylation and ERK1/2 and AKT activity in mammary tumors. Long-term TKI258 treatment of 4T1 tumor- and 67NR tumor-bearing mice had a significant effect on primary tumor outgrowth and 4T1 tumor-induced lung metastases. A microarray analysis was carried out to identify targets with roles in TKI258 antitumor activity and potential prognostic markers in human breast tumors. Of interest are the downregulated matrix metalloproteases (MMP), in particular MMP9, which is essential for metastatic spread of 4T1 tumors. (c)2010 AACR.
V S, Unni; Mishra, Deepak; Subrahmanyam, G R K S
2016-12-01
The need for image fusion in current image processing systems is increasing mainly due to the increased number and variety of image acquisition techniques. Image fusion is the process of combining substantial information from several sensors using mathematical techniques in order to create a single composite image that will be more comprehensive and thus more useful for a human operator or other computer vision tasks. This paper presents a new approach to multifocus image fusion based on sparse signal representation. Block-based compressive sensing integrated with a projection-driven compressive sensing (CS) recovery that encourages sparsity in the wavelet domain is used as a method to get the focused image from a set of out-of-focus images. Compression is achieved during the image acquisition process using a block compressive sensing method. An adaptive thresholding technique within the smoothed projected Landweber recovery process reconstructs high-resolution focused images from low-dimensional CS measurements of out-of-focus images. Discrete wavelet transform and dual-tree complex wavelet transform are used as the sparsifying basis for the proposed fusion. The main finding lies in the fact that sparsification enables a better selection of the fusion coefficients and hence better fusion. A Laplacian mixture model fit is done in the wavelet domain and estimation of the probability density function (pdf) parameters by expectation maximization leads us to the proper selection of the coefficients of the fused image. Using the proposed method compared with the fusion scheme without employing the projected Landweber (PL) scheme and the other existing CS-based fusion approaches, it is observed that with fewer samples itself, the proposed method outperforms other approaches.
1993-01-01
external parameters such as airflow, temperature, pressure, etc, are measured. Turbine Engine testing generates massive volumes of data at very high...a form that describes the signal flow graph topology as well as specific parameters of the processing blocks in the diagram. On multiprocessor...provides an interface to the symbolic builder and control functions such that parameters may be set during the build operation that will affect the
Sphingosine kinase-1 mediates androgen-induced osteoblast cell growth
DOE Office of Scientific and Technical Information (OSTI.GOV)
Martin, Claire; Universite de Toulouse, UPS, IPBS, Toulouse F-31000; Lafosse, Jean-Michel
Herein we report that the lipid kinase sphingosine kinase-1 (SphK1) is instrumental in mediating androgen-induced cell proliferation in osteoblasts. Dihydrotestosterone (DHT) triggered cell growth in steroid-deprived MC3T3 cells, which was associated with a rapid stimulation of SphK1 and activation of both Akt and ERK signaling pathways. This mechanism relied on functional androgen receptor/PI3K/Akt nongenotropic signaling as pharmacological antagonists could block SphK1 stimulation by DHT and its consequences. Finally, SphK1 inhibition not only abrogated DHT-induced ERK activation but also blocked cell proliferation, while ERK inhibition had no impact, suggesting that SphK1 was critical for DHT signaling yet independently of the ERK.
Truck circuits diagnosis for railway lines equipped with an automatic block signalling system
NASA Astrophysics Data System (ADS)
Spunei, E.; Piroi, I.; Muscai, C.; Răduca, E.; Piroi, F.
2018-01-01
This work presents a diagnosis method for detecting track circuits failures on a railway traffic line equipped with an Automatic Block Signalling installation. The diagnosis method uses the installation’s electrical schemas, based on which a series of diagnosis charts have been created. Further, the diagnosis charts were used to develop a software package, CDCBla, which substantially contributes to reducing the diagnosis time and human error during failure remedies. The proposed method can also be used as a training package for the maintenance staff. Since the diagnosis method here does not need signal or measurement inputs, using it does not necessitate additional IT knowledge and can be deployed on a mobile computing device (tablet, smart phone).
McCormick, Frank
2015-04-15
KRAS proteins play a major role in human cancer, but have not yielded to therapeutic attack. New technologies in drug discovery and insights into signaling pathways that KRAS controls have promoted renewed efforts to develop therapies through direct targeting of KRAS itself, new ways of blocking KRAS processing, or by identifying targets that KRAS cancers depend on for survival. Although drugs that block the well-established downstream pathways, RAF-MAPK and PI3K, are being tested in the clinic, new efforts are under way to exploit previously unrecognized vulnerabilities, such as altered metabolic networks, or novel pathways identified through synthetic lethal screens. Furthermore, new ways of suppressing KRAS gene expression and of harnessing the immune system offer further hope that new ways of treating KRAS are finally coming into view. These issues are discussed in this edition of CCR Focus. ©2015 American Association for Cancer Research.
Morshed, S. A.; Davies, T. F.
2016-01-01
The immunologic processes involved in Graves' disease (GD) have one unique characteristic – the autoantibodies to the TSH receptor (TSHR) – which have both linear and conformational epitopes. Three types of TSHR antibodies (stimulating, blocking, and cleavage) with different functional capabilities have been described in GD patients, which induce different signaling effects varying from thyroid cell proliferation to thyroid cell death. The establishment of animal models of GD by TSHR antibody transfer or by immunization with TSHR antigen has confirmed its pathogenic role and, therefore, GD is the result of a breakdown in TSHR tolerance. Here we review some of the characteristics of TSHR antibodies with a special emphasis on new developments in our understanding of what were previously called “neutral” antibodies and which we now characterize as autoantibodies to the “cleavage” region of the TSHR ectodomain. PMID:26361259
NASA Astrophysics Data System (ADS)
Sawczuk, Wojciech
2017-06-01
Due to their wide range of friction characteristics resulting from the application of different friction materials and good heat dissipation conditions, railway disc brakes have long replaced block brakes in many rail vehicles. A block brake still remains in use, however, in low speed cargo trains. The paper presents the assessment of the braking process through the analysis of vibrations generated by the components of the brake system during braking. It presents a possibility of a wider application of vibroacoustic diagnostics (VA), which aside from the assessment of technical conditions (wear of brake pads) also enables the determination of the changes of the average friction coefficient as a function of the braking onset speed. Vibration signals of XYZ were measured and analyzed. The analysis of the results has shown that there is a relation between the values of the point measures and the wear of the brake pads.
NASA Astrophysics Data System (ADS)
Sasaki, Toshihiko; Koashi, Masato
2017-06-01
The round-robin differential phase shift (RRDPS) quantum key distribution (QKD) protocol is a unique QKD protocol whose security has not been understood through an information-disturbance trade-off relation, and a sufficient amount of privacy amplification was given independently of signal disturbance. Here, we discuss the security of the RRDPS protocol in the asymptotic regime when a good estimate of the bit error rate is available as a measure of signal disturbance. The uniqueness of the RRDPS protocol shows up as a peculiar form of information-disturbance trade-off curve. When the length of a block of pulses used for encoding and the signal disturbance are both small, it provides a significantly better key rate than that from the original security proof. On the other hand, when the block length is large, the use of the signal disturbance makes little improvement in the key rate. Our analysis will bridge a gap between the RRDPS protocol and the conventional QKD protocols.
Qin, Jian; Lin, Yulian; Norman, Ryan X; Ko, Hyuk W; Eggenschwiler, Jonathan T
2011-01-25
Primary cilia are required for proper Sonic Hedgehog (Shh) signaling in mammals. However, their role in the signal transduction process remains unclear. We have identified sister of open brain (sopb), a null allele of mouse Intraflagellar transport protein 122 (Ift122). IFT122 negatively regulates the Shh pathway in the cilium at a step downstream of the Shh ligand and the transmembrane protein Smoothened, but upstream of the Gli2 transcription factor. Ift122(sopb) mutants generate primary cilia, but they show features of defective retrograde intraflagellar transport. IFT122 controls the ciliary localization of Shh pathway regulators in different ways. Disruption of IFT122 leads to accumulation of Gli2 and Gli3 at cilia tips while blocking the ciliary localization of the antagonist TULP3. Suppressor of Fused and Smoothened localize to the cilium through an IFT122-independent mechanism. We propose that the balance between positive and negative regulators of the Shh pathway at the cilium tip controls the output of the pathway and that Shh signaling regulates this balance through intraflagellar transport.
Drug Modulators of B Cell Signaling Pathways and Epstein-Barr Virus Lytic Activation.
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.
Bouwer, James C; Deerinck, Thomas J; Bushong, Eric; Astakhov, Vadim; Ramachandra, Ranjan; Peltier, Steven T; Ellisman, Mark H
2017-01-01
Serial block-face scanning electron microscopy (SBEM) is quickly becoming an important imaging tool to explore three-dimensional biological structure across spatial scales. At probe-beam-electron energies of 2.0 keV or lower, the axial resolution should improve, because there is less primary electron penetration into the block face. More specifically, at these lower energies, the interaction volume is much smaller, and therefore, surface detail is more highly resolved. However, the backscattered electron yield for metal contrast agents and the backscattered electron detector sensitivity are both sub-optimal at these lower energies, thus negating the gain in axial resolution. We found that the application of a negative voltage (reversal potential) applied to a modified SBEM stage creates a tunable electric field at the sample. This field can be used to decrease the probe-beam-landing energy and, at the same time, alter the trajectory of the signal to increase the signal collected by the detector. With decelerated low landing-energy electrons, we observed that the probe-beam-electron-penetration depth was reduced to less than 30 nm in epoxy-embedded biological specimens. Concurrently, a large increase in recorded signal occurred due to the re-acceleration of BSEs in the bias field towards the objective pole piece where the detector is located. By tuning the bias field, we were able to manipulate the trajectories of the primary and secondary electrons, enabling the spatial discrimination of these signals using an advanced ring-type BSE detector configuration or a standard monolithic BSE detector coupled with a blocking aperture.
Fgf Signaling is Required for Photoreceptor Maintenance in the Adult Zebrafish Retina
Hochmann, Sarah; Kaslin, Jan; Hans, Stefan; Weber, Anke; Machate, Anja; Geffarth, Michaela; Funk, Richard H. W.; Brand, Michael
2012-01-01
Fibroblast growth factors (Fgf) are secreted signaling molecules that have mitogenic, patterning, neurotrophic and angiogenic properties. Their importance during embryonic development in patterning and morphogenesis of the vertebrate eye is well known, but less is known about the role of Fgfs in the adult vertebrate retina. To address Fgf function in adult retina, we determined the spatial distribution of components of the Fgf signaling pathway in the adult zebrafish retina. We detected differential expression of Fgf receptors, ligands and downstream Fgf targets within specific retinal layers. Furthermore, we blocked Fgf signaling in the retina, by expressing a dominant negative variant of Fgf receptor 1 conditionally in transgenic animals. After blocking Fgf signaling we observe a fast and progressive photoreceptor degeneration and disorganization of retinal tissue, coupled with cell death in the outer nuclear layer. Following the degeneration of photoreceptors, a profound regeneration response is triggered that starts with proliferation in the inner nuclear layer. Ultimately, rod and cone photoreceptors are regenerated completely. Our study reveals the requirement of Fgf signaling to maintain photoreceptors and for proliferation during regeneration in the adult zebrafish retina. PMID:22291943
Ski represses BMP signaling in Xenopus and mammalian cells
DOE Office of Scientific and Technical Information (OSTI.GOV)
kluo@lbl.gov
2001-05-16
The bone morphogenic proteins (BMPs) play important roles in vertebrate development. In Xenopus, BMPs act as epidermal inducers and also as negative regulators of neurogenesis. Antagonism of BMP signaling results in neuralization. BMPs signal through the cell-surface receptors and downstream Smad molecules. Upon stimulation with BMP, Smad1, Smad5, and Smad8 are phosphorylated by the activated BMP receptors, form a complex with Smad4, and translocate into the nucleus, where they regulate the expression of BMP target genes. Here, we show that the Ski oncoprotein can block BMP signaling and the expression of BMP-responsive genes in both Xenopus and mammalian cells bymore » directly interacting with and repressing the activity of BMP-specific Smad complexes. This ability to antagonize BMP signaling results in neuralization by Ski in the Xenopus embryo and blocking of osteoblast differentiation of murine W-20-17 cells. Thus, Ski is able to repress the activity of all receptor-associated Smads and may regulate vertebrate development by modulating the signaling activity of transforming growth factor-{beta} family members.« less
Ski represses bone morphogenic protein signaling in Xenopus and mammalian cells
Wang, Wei; Mariani, Francesca V.; Harland, Richard M.; Luo, Kunxin
2000-01-01
The bone morphogenic proteins (BMPs) play important roles in vertebrate development. In Xenopus, BMPs act as epidermal inducers and also as negative regulators of neurogenesis. Antagonism of BMP signaling results in neuralization. BMPs signal through the cell-surface receptors and downstream Smad molecules. Upon stimulation with BMP, Smad1, Smad5, and Smad8 are phosphorylated by the activated BMP receptors, form a complex with Smad4, and translocate into the nucleus, where they regulate the expression of BMP target genes. Here, we show that the Ski oncoprotein can block BMP signaling and the expression of BMP-responsive genes in both Xenopus and mammalian cells by directly interacting with and repressing the activity of BMP-specific Smad complexes. This ability to antagonize BMP signaling results in neuralization by Ski in the Xenopus embryo and blocking of osteoblast differentiation of murine W-20-17 cells. Thus, Ski is able to repress the activity of all receptor-associated Smads and may regulate vertebrate development by modulating the signaling activity of transforming growth factor-β family members. PMID:11121043
Ski represses bone morphogenic protein signaling in Xenopus and mammalian cells.
Wang, W; Mariani, F V; Harland, R M; Luo, K
2000-12-19
The bone morphogenic proteins (BMPs) play important roles in vertebrate development. In Xenopus, BMPs act as epidermal inducers and also as negative regulators of neurogenesis. Antagonism of BMP signaling results in neuralization. BMPs signal through the cell-surface receptors and downstream Smad molecules. Upon stimulation with BMP, Smad1, Smad5, and Smad8 are phosphorylated by the activated BMP receptors, form a complex with Smad4, and translocate into the nucleus, where they regulate the expression of BMP target genes. Here, we show that the Ski oncoprotein can block BMP signaling and the expression of BMP-responsive genes in both Xenopus and mammalian cells by directly interacting with and repressing the activity of BMP-specific Smad complexes. This ability to antagonize BMP signaling results in neuralization by Ski in the Xenopus embryo and blocking of osteoblast differentiation of murine W-20-17 cells. Thus, Ski is able to repress the activity of all receptor-associated Smads and may regulate vertebrate development by modulating the signaling activity of transforming growth factor-beta family members.
Schmitt, Hannah; Kray, Jutta; Ferdinand, Nicola K.
2017-01-01
A number of aging studies suggest that older adults process positive and negative information differently. For instance, the socioemotional selectivity theory postulates that older adults preferably process positive information in service of emotional well-being (Reed and Carstensen, 2012). Moreover, recent research has started to investigate whether incentives like gains or losses can influence cognitive control in an ongoing task. In an earlier study (Schmitt et al., 2015), we examined whether incentive cues, indicating potential monetary gains, losses, or neutral outcomes for good performance in the following trial, would influence older adults’ ability to exert cognitive control. Cognitive control was measured in an AX-Continuous-Performance-Task (AX-CPT) in which participants had to select their responses to probe stimuli depending on a preceding context cue. In this study, we did not find support for a positivity effect in older adults, but both gains and losses led to enhanced context processing. As the trial-wise presentation mode may be too demanding on cognitive resources for such a bias to occur, the main goal of the present study was to examine whether motivational mindsets, induced by block-wise presentation of incentives, would result in a positivity effect. For this reason, we examined 17 older participants (65–76 years) in the AX-CPT using a block-wise presentation of incentive cues and compared them to 18 older adults (69–78 years) with the trial-wise presentation mode from our earlier study (Schmitt et al., 2015). Event-related potentials were recorded to the onset of the motivational cue and during the AX-CPT. Our results show that (a) older adults initially process cues signaling potential losses more strongly, but later during the AX-CPT invest more cognitive resources in preparatory processes like context updating in conditions with potential gains, and (b) block-wise and trial-wise presentation of incentive cues differentially influenced cognitive control. When incentives were presented block-wise, the above described valence effects were consistently found. In contrast, when incentives were presented trial-wise, the effects were mixed and salience as well as valence effects can be obtained. Hence, how positive and negative incentive cues influence cognitive control in older adults is dependent on demands of cue processing. PMID:29170649
Schmitt, Hannah; Kray, Jutta; Ferdinand, Nicola K
2017-01-01
A number of aging studies suggest that older adults process positive and negative information differently. For instance, the socioemotional selectivity theory postulates that older adults preferably process positive information in service of emotional well-being (Reed and Carstensen, 2012). Moreover, recent research has started to investigate whether incentives like gains or losses can influence cognitive control in an ongoing task. In an earlier study (Schmitt et al., 2015), we examined whether incentive cues, indicating potential monetary gains, losses, or neutral outcomes for good performance in the following trial, would influence older adults' ability to exert cognitive control. Cognitive control was measured in an AX-Continuous-Performance-Task (AX-CPT) in which participants had to select their responses to probe stimuli depending on a preceding context cue. In this study, we did not find support for a positivity effect in older adults, but both gains and losses led to enhanced context processing. As the trial-wise presentation mode may be too demanding on cognitive resources for such a bias to occur, the main goal of the present study was to examine whether motivational mindsets, induced by block-wise presentation of incentives, would result in a positivity effect. For this reason, we examined 17 older participants (65-76 years) in the AX-CPT using a block-wise presentation of incentive cues and compared them to 18 older adults (69-78 years) with the trial-wise presentation mode from our earlier study (Schmitt et al., 2015). Event-related potentials were recorded to the onset of the motivational cue and during the AX-CPT. Our results show that (a) older adults initially process cues signaling potential losses more strongly, but later during the AX-CPT invest more cognitive resources in preparatory processes like context updating in conditions with potential gains, and (b) block-wise and trial-wise presentation of incentive cues differentially influenced cognitive control. When incentives were presented block-wise, the above described valence effects were consistently found. In contrast, when incentives were presented trial-wise, the effects were mixed and salience as well as valence effects can be obtained. Hence, how positive and negative incentive cues influence cognitive control in older adults is dependent on demands of cue processing.
RETRACTED ARTICLE: Quorum-sensing of bacteria and its application
NASA Astrophysics Data System (ADS)
Jiang, Guoliang; Su, Mingxia
2009-12-01
Quorum sensing, or auto induction, as a cell density dependent signaling mechanism in many microorganisms, is triggered via auto inducers which passively diffuse across the bacterial envelope and therefore intracellulaly accumulate only at higher bacterial densities to regulate specialized processes such as genetic competence, bioluminescence, virulence and sporulation. N-acyl homoserine lactones are the most common type of signal molecules. Aquaculture is one of the fastest-growing food-producing industries, but disease outbreaks caused by pathogenic bacteria are a significant constraint on the development of the sector worldwide. Many of these pathogens have been found to be controlled by their quorum sensing systems. As there is relevance between the pathogenic bacteria's virulence factor expression and their auto inducers, quorum quenching is a new effective anti-infective strategy to control infections caused by bacterial pathogens in aquaculture. The techniques used to do this mainly include the following: (1) the inhibition of signal molecule biosynthesis, (2) blocking signal transduction, and (3) chemical inactivation and biodegradation of signal molecules. To provide a basis for finding alternative means of controlling aquatic diseases by quorum quenching instead of treatment by antibiotics and disinfectants, we will discuss the examination, purification and identification of auto inducers in this paper.
Covert laser remote sensing and vibrometry
NASA Technical Reports Server (NTRS)
Maleki, Lutfollah (Inventor); Yu, Nan (Inventor); Matsko, Andrey B. (Inventor); Savchenkov, Anatoliy (Inventor)
2012-01-01
Designs of single-beam laser vibrometry systems and methods. For example, a method for detecting vibrations of a target based on optical sensing is provided to include operating a laser to produce a laser probe beam at a laser frequency and modulated at a modulation frequency onto a target; collecting light at or near the laser to collect light from the target while the target is being illuminated by the laser probe beam through an optical receiver aperture; using a narrow-band optical filter centered at the laser frequency to filter light collected from the optical receiver aperture to transmit light at the laser frequency while blocking light at other frequencies; using an optical detector to convert filtered light from the narrow-band optical filter to produce a receiver electrical signal; using a lock-in amplifier to detect and amplify the receiver electrical signal at the modulation frequency while rejecting signal components at other frequencies to produce an amplified receiver electrical signal; processing the amplified receiver electrical signal to extract information on vibrations of the target carried by reflected laser probe beam in the collected light; and controlling optical power of the laser probe beam at the target to follow optical power of background illumination at the target.
Wischin, Sabina; Castañeda-Patlán, Cristina; Robles-Flores, Martha; Chimal-Monroy, Jesús
2017-04-01
Limb regeneration involves several interrelated physiological processes in which a particular signalling pathway may play a variety of functions. Blocking the function of Wnt/β-catenin signalling during limb regeneration inhibits regeneration in axolotls (Ambystoma mexicanum). Limb development shares many features with limb regeneration, and Wnt/β-catenin activation has different effects depending on the developmental stage. The aim of this study was to evaluate whether Wnt/β-catenin signalling activation during axolotl limb regeneration has different effects when activated at different stages of regeneration. To evaluate this hypothesis, we treated amputated axolotls with a Wnt agonist chemical at different stages of limb regeneration. The results showed that limb regeneration was inhibited when the treatment began before blastema formation. Under these conditions, blastema formation was hindered, possibly due to the lack of innervation. On the other hand, when axolotls were treated after blastema formation and immediately before the onset of morphogenesis, we observed structural disorganization in skeletal formation. In conclusion, we found that limb regeneration was differentially affected depending on the stage at which the Wnt signalling pathway was activated. Copyright © 2017 Elsevier B.V. All rights reserved.
Zhang, Yonglong; Patidar, Ashish; Vilar, Enric; Finkelman, Malcolm; Farrington, Ken
2016-01-01
Background Elevated blood endotoxin levels are frequently reported in the dialysis population and are strongly linked with inflammation, a major predictor of mortality. Virtually all studies have employed the Limulus Amoebocyte Lysate (LAL) assay to detect endotoxin. However this assay is not endotoxin-specific and can be activated by (1→3)-β-glucan (BG), a component of fungal cell walls leading to false positive signals. Very few studies have taken account of this. We examined the influence of BG-based activation of the LAL assay on the detection of endotoxemia in this setting. Method We measured plasma endotoxin levels in 50 hemodialysis patients with and without the use of BG-blocking buffers. These buffers inhibit BG activation of the LAL assay to ensure that any signal detected is endotoxin-specific. Blood samples were measured for BG, interleukin-6 (IL-6), tumor necrosis factor-alfa (TNF-α) to examine the association between endotoxin signals, BG and inflammation. Results Endotoxin signals were detected in 50% of patients. On repeat measurement with a BG-blocking buffer, all detected endotoxin signals were extinguished. No patient had detectable endotoxemia. Plasma BG levels were significantly elevated in 58% of patients and were higher in those with detectable endotoxin signals using the LAL assay without BG-blocking buffers (78vs.54pg/mL;p<0.001). Endotoxin signal and BG levels did not correlate with levels of TNF-α or IL-6. Conclusion Use of the LAL assay for blood endotoxin detection in dialysis patients has its limitations due to high blood BG. Endotoxemia frequently reported in non-infected hemodialysis patients may be artefactual due to BG interference. PMID:27764208
Liu, Pei-Shan; Chueh, Sheau-Huei; Chen, Chin-Chu; Lee, Li-Ya; Shiu, Li-Yen
2017-01-01
Hericium erinaceus is well known for the neurotrophic effect it confers by promoting nerve growth factor biosynthesis. We discovered a novel bioactivity of H. erinaceus in its ability to suppress adenosine triphosphate (ATP)-induced calcium signaling in neuronal PC12 cells. ATP, known primarily as a neurotransmitter, also acts on purinoceptors (P2 purinergic receptor [P2R]) to generate the cellular calcium signaling and secretion that mediate P2R physiological manifestations, including pain. Chronic pain reduces quality of life. However, constant analgesic administration can cause liver and kidney injury, as well as loss of the analgesic effect because of desensitization. In this study we investigated the analgesic potential of H. erinaceus through measurements of ATP-induced Ca2+ signaling in cell lines and observation of pain behaviors in mice. In P2R-coupled Ca2+ signaling measurements, extracts of H. erinaceus mycelia (HEEs) blocked ATP-induced Ca2+ signaling in both rat PC12 cells and human HOS cells. HEEs completely blocked ATP-induced Ca2+ signaling in human HOS cells, suggesting that this effect of HEEs is exerted through the P2R subtypes present in HOS cells, which include the P2X4, P2X7, P2Y2, and P2Y4 subtypes. In observations of animal behavior during pain, HEEs significantly reduced heat-induced pain, including postponing both the tail-flick response to heat stimulation and the paw-lifting response to a hot plate. This study demonstrates novel characteristics of H. erinaceus in reducing nociceptive behavior and blocking the functional activity of P2R. Further studies are required to verify this linkage and its molecular mechanisms.
2008-06-01
provide the coverage. To enable weak GPS signal acquisition , one known technique at the receiver end is to extend the signal integration time...Han, “Block Accumulating Coherent Integration Over Extended Interval (BACIX) for Weak GPS Signal Acquisition ,” Proc. of ION-GNSS’06, Ft. Worth, TX...AFRL-RY-WP-TP-2008-1158 POST-CORRELATION SEMI-COHERENT INTEGRATION FOR HIGH-DYNAMIC AND WEAK GPS SIGNAL ACQUISITION (PREPRINT) Chun Yang
On the Application of Time-Reversed Space-Time Block Code to Aeronautical Telemetry
2014-06-01
Keying (SOQPSK), bit error rate (BER), Orthogonal Frequency Division Multiplexing ( OFDM ), Generalized time-reversed space-time block codes (GTR-STBC) 16...Alamouti code [4]) is optimum [2]. Although OFDM is generally applied on a per subcarrier basis in frequency selective fading, it is not a viable...Calderbank, “Finite-length MIMO decision feedback equal- ization for space-time block-coded signals over multipath-fading channels,” IEEE Transac- tions on
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ma, Xusheng, E-mail: maxushengtt@163.com; Yang, Xing; Nian, Xiaofeng
Peste des petits ruminants virus (PPRV) causes a fatal disease in small ruminants. V protein of PPRV plays a pivotal role in interfering with host innate immunity by blocking IFNs signaling through interacting with STAT1 and STAT2. In the present study, the results demonstrated that PPRV V protein blocks IFN actions in a dose dependent manner and restrains the translocation of STAT1/2 proteins. We speculate that the translocation inhibition might be caused by the interfering of the downstream of STAT protein. Mutagenesis defines that Cys cluster and Trp motif of PPRV V protein are essential for STAT-mediated IFN signaling. Thesemore » findings give a new sight for the further studies to understand the delicate mechanism of PPRV to escape the IFN signaling. - Highlights: • PPRV V protein inhibits type I IFN production and blocks its activation. • PPRV V protein negatively regulates activation of ISRE and GAS promoter. • PPRV V protein inhibits nuclear translocation of STAT protein by non-degradation. • PNT and VCT domain of PPRV V protein inhibit IFN transduction. • PPRV V protein binds with STAT protein via some conserved motifs.« less
Lu, Wenyan; Liu, Chia-Chen; Thottassery, Jaideep V.; Bu, Guojun; Li, Yonghe
2010-01-01
Mesd is a specialized chaperone for the low-density lipoprotein receptor-related protein-5 (LRP5) and LRP6. In our previous studies, we found that Mesd binds to mature LRP6 on the cell surface and blocks the binding of Wnt antagonist Dickkopf-1(Dkk1) to LRP6. Herein, we demonstrated that Mesd also binds to LRP5 with a high affinity, and is a universal inhibitor of LRP5/6 ligands. Mesd not only blocks Wnt antagonists Dkk1 and Sclerostin binding to LRP5/6, but also inhibits Wnt3A and Rspondin1-induced Wnt/β-catenin signaling in LRP5/6 expressing cells. We also found that Mesd, Dkk1 and Sclerostin compete with one another for binding to LRP5 and LRP6 at the cell surface. More importantly, we demonstrated that Mesd is able to suppress LRP6 phosphorylation and Wnt/β-catenin signaling in prostate cancer PC-3 cells, and inhibits PC-3 cell proliferation. Our results indicate that recombinant Mesd protein is a useful tool for studying Wnt/β-catenin signaling on the cell surface, and has a potential therapeutic role in Wnt-dependent cancers. PMID:20446724
On the application of under-decimated filter banks
NASA Technical Reports Server (NTRS)
Lin, Y.-P.; Vaidyanathan, P. P.
1994-01-01
Maximally decimated filter banks have been extensively studied in the past. A filter bank is said to be under-decimated if the number of channels is more than the decimation ratio in the subbands. A maximally decimated filter bank is well known for its application in subband coding. Another application of maximally decimated filter banks is in block filtering. Convolution through block filtering has the advantages that parallelism is increased and data are processed at a lower rate. However, the computational complexity is comparable to that of direct convolution. More recently, another type of filter bank convolver has been developed. In this scheme, the convolution is performed in the subbands. Quantization and bit allocation of subband signals are based on signal variance, as in subband coding. Consequently, for a fixed rate, the result of convolution is more accurate than is direct convolution. This type of filter bank convolver also enjoys the advantages of block filtering, parallelism, and a lower working rate. Nevertheless, like block filtering, there is no computational saving. In this article, under-decimated systems are introduced to solve the problem. The new system is decimated only by half the number of channels. Two types of filter banks can be used in the under-decimated system: the discrete Fourier transform (DFT) filter banks and the cosine modulated filter banks. They are well known for their low complexity. In both cases, the system is approximately alias free, and the overall response is equivalent to a tunable multilevel filter. Properties of the DFT filter banks and the cosine modulated filter banks can be exploited to simultaneously achieve parallelism, computational saving, and a lower working rate. Furthermore, for both systems, the implementation cost of the analysis or synthesis bank is comparable to that of one prototype filter plus some low-complexity modulation matrices. The individual analysis and synthesis filters have complex coefficients in the DFT filter banks but have real coefficients in the cosine modulated filter banks.
On the application of under-decimated filter banks
NASA Astrophysics Data System (ADS)
Lin, Y.-P.; Vaidyanathan, P. P.
1994-11-01
Maximally decimated filter banks have been extensively studied in the past. A filter bank is said to be under-decimated if the number of channels is more than the decimation ratio in the subbands. A maximally decimated filter bank is well known for its application in subband coding. Another application of maximally decimated filter banks is in block filtering. Convolution through block filtering has the advantages that parallelism is increased and data are processed at a lower rate. However, the computational complexity is comparable to that of direct convolution. More recently, another type of filter bank convolver has been developed. In this scheme, the convolution is performed in the subbands. Quantization and bit allocation of subband signals are based on signal variance, as in subband coding. Consequently, for a fixed rate, the result of convolution is more accurate than is direct convolution. This type of filter bank convolver also enjoys the advantages of block filtering, parallelism, and a lower working rate. Nevertheless, like block filtering, there is no computational saving. In this article, under-decimated systems are introduced to solve the problem. The new system is decimated only by half the number of channels. Two types of filter banks can be used in the under-decimated system: the discrete Fourier transform (DFT) filter banks and the cosine modulated filter banks. They are well known for their low complexity. In both cases, the system is approximately alias free, and the overall response is equivalent to a tunable multilevel filter. Properties of the DFT filter banks and the cosine modulated filter banks can be exploited to simultaneously achieve parallelism, computational saving, and a lower working rate.
49 CFR 231.16 - Steam locomotives used in switching service.
Code of Federal Regulations, 2013 CFR
2013-10-01
... clearance. No part of locomotive or tender except draft rigging, coupler and attachments, safety chains, buffer block, footboard, brake pipe, signal pipe, steam-heat pipe or arms of uncoupling lever shall... with horn of coupler against buffer block or end sill. (h) Couplers. Locomotives shall be equipped with...
49 CFR 231.16 - Steam locomotives used in switching service.
Code of Federal Regulations, 2011 CFR
2011-10-01
... clearance. No part of locomotive or tender except draft rigging, coupler and attachments, safety chains, buffer block, footboard, brake pipe, signal pipe, steam-heat pipe or arms of uncoupling lever shall... with horn of coupler against buffer block or end sill. (h) Couplers. Locomotives shall be equipped with...
49 CFR 231.16 - Steam locomotives used in switching service.
Code of Federal Regulations, 2014 CFR
2014-10-01
... clearance. No part of locomotive or tender except draft rigging, coupler and attachments, safety chains, buffer block, footboard, brake pipe, signal pipe, steam-heat pipe or arms of uncoupling lever shall... with horn of coupler against buffer block or end sill. (h) Couplers. Locomotives shall be equipped with...
49 CFR 231.16 - Steam locomotives used in switching service.
Code of Federal Regulations, 2012 CFR
2012-10-01
... clearance. No part of locomotive or tender except draft rigging, coupler and attachments, safety chains, buffer block, footboard, brake pipe, signal pipe, steam-heat pipe or arms of uncoupling lever shall... with horn of coupler against buffer block or end sill. (h) Couplers. Locomotives shall be equipped with...
49 CFR 231.16 - Steam locomotives used in switching service.
Code of Federal Regulations, 2010 CFR
2010-10-01
... clearance. No part of locomotive or tender except draft rigging, coupler and attachments, safety chains, buffer block, footboard, brake pipe, signal pipe, steam-heat pipe or arms of uncoupling lever shall... with horn of coupler against buffer block or end sill. (h) Couplers. Locomotives shall be equipped with...
Calcium-Induced Calcium Release during Action Potential Firing in Developing Inner Hair Cells
Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J.
2015-01-01
In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights into the calcium signaling mechanisms involved in early developmental processes. PMID:25762313
Calcium-Induced calcium release during action potential firing in developing inner hair cells.
Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J
2015-03-10
In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights into the calcium signaling mechanisms involved in early developmental processes. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Mansukhani, Alka; Bellosta, Paola; Sahni, Malika; Basilico, Claudio
2000-01-01
Fibroblast growth factors (FGF) play a critical role in bone growth and development affecting both chondrogenesis and osteogenesis. During the process of intramembranous ossification, which leads to the formation of the flat bones of the skull, unregulated FGF signaling can produce premature suture closure or craniosynostosis and other craniofacial deformities. Indeed, many human craniosynostosis disorders have been linked to activating mutations in FGF receptors (FGFR) 1 and 2, but the precise effects of FGF on the proliferation, maturation and differentiation of the target osteoblastic cells are still unclear. In this report, we studied the effects of FGF treatment on primary murine calvarial osteoblast, and on OB1, a newly established osteoblastic cell line. We show that FGF signaling has a dual effect on osteoblast proliferation and differentiation. FGFs activate the endogenous FGFRs leading to the formation of a Grb2/FRS2/Shp2 complex and activation of MAP kinase. However, immature osteoblasts respond to FGF treatment with increased proliferation, whereas in differentiating cells FGF does not induce DNA synthesis but causes apoptosis. When either primary or OB1 osteoblasts are induced to differentiate, FGF signaling inhibits expression of alkaline phosphatase, and blocks mineralization. To study the effect of craniosynostosis-linked mutations in osteoblasts, we introduced FGFR2 carrying either the C342Y (Crouzon syndrome) or the S252W (Apert syndrome) mutation in OB1 cells. Both mutations inhibited differentiation, while dramatically inducing apoptosis. Furthermore, we could also show that overexpression of FGF2 in transgenic mice leads to increased apoptosis in their calvaria. These data provide the first biochemical analysis of FGF signaling in osteoblasts, and show that FGF can act as a cell death inducer with distinct effects in proliferating and differentiating osteoblasts. PMID:10851026
Xue, Qi; Hopkins, Benjamin; Perruzzi, Carole; Udayakumar, Durga; Sherris, David; Benjamin, Laura E.
2009-01-01
It has become clear that the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is central for promoting both tumor and tumor stroma and is therefore a major target for anticancer drug development. First- and second-generation rapalogs (prototypical mTOR inhibitors) have shown promise but, due to the complex nature of mTOR signaling, can result in counterproductive feedback signaling to potentiate upstream Akt signaling. We present a novel PI3K/Akt/mTOR inhibitor, Palomid 529 (P529), which inhibits the TORC1 and TORC2 complexes and shows both inhibition of Akt signaling and mTOR signaling similarly in tumor and vasculature. We show that P529 inhibits tumor growth, angiogenesis, and vascular permeability. It retains the beneficial aspects of tumor vascular normalization that rapamycin boasts. However, P529 has the additional benefit of blocking pAktS473 signaling consistent with blocking TORC2 in all cells and thus bypassing feedback loops that lead to increased Akt signaling in some tumor cells. [Cancer Res 2008;68(22):9551–7] PMID:19010932
49 CFR 236.15 - Timetable instructions.
Code of Federal Regulations, 2011 CFR
2011-10-01
..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Rules and Instructions: All Systems General § 236.15 Timetable instructions. Automatic block, traffic control, train stop, train control and cab signal territory shall be designated in timetable instructions. ...
49 CFR 236.15 - Timetable instructions.
Code of Federal Regulations, 2010 CFR
2010-10-01
..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Rules and Instructions: All Systems General § 236.15 Timetable instructions. Automatic block, traffic control, train stop, train control and cab signal territory shall be designated in timetable instructions. ...
Evaluation of Urban Freight Deliveries using Microsimulation and Surrogate Safety Measures
DOT National Transportation Integrated Search
2018-02-01
Freight deliveries on signalized urban streets are known to cause lane blockages during deliveries. When delivery vehicles block lanes of traffic near signalized intersections, the capacity of the intersection is affected. Current practice is for tra...
Seamless contiguity method for parallel segmentation of remote sensing image
NASA Astrophysics Data System (ADS)
Wang, Geng; Wang, Guanghui; Yu, Mei; Cui, Chengling
2015-12-01
Seamless contiguity is the key technology for parallel segmentation of remote sensing data with large quantities. It can be effectively integrate fragments of the parallel processing into reasonable results for subsequent processes. There are numerous methods reported in the literature for seamless contiguity, such as establishing buffer, area boundary merging and data sewing. et. We proposed a new method which was also based on building buffers. The seamless contiguity processes we adopt are based on the principle: ensuring the accuracy of the boundary, ensuring the correctness of topology. Firstly, block number is computed based on data processing ability, unlike establishing buffer on both sides of block line, buffer is established just on the right side and underside of the line. Each block of data is segmented respectively and then gets the segmentation objects and their label value. Secondly, choose one block(called master block) and do stitching on the adjacent blocks(called slave block), process the rest of the block in sequence. Through the above processing, topological relationship and boundaries of master block are guaranteed. Thirdly, if the master block polygons boundaries intersect with buffer boundary and the slave blocks polygons boundaries intersect with block line, we adopt certain rules to merge and trade-offs them. Fourthly, check the topology and boundary in the buffer area. Finally, a set of experiments were conducted and prove the feasibility of this method. This novel seamless contiguity algorithm provides an applicable and practical solution for efficient segmentation of massive remote sensing image.
Baddeley, Michelle; Tobler, Philippe N.; Schultz, Wolfram
2016-01-01
Given that the range of rewarding and punishing outcomes of actions is large but neural coding capacity is limited, efficient processing of outcomes by the brain is necessary. One mechanism to increase efficiency is to rescale neural output to the range of outcomes expected in the current context, and process only experienced deviations from this expectation. However, this mechanism comes at the cost of not being able to discriminate between unexpectedly low losses when times are bad versus unexpectedly high gains when times are good. Thus, too much adaptation would result in disregarding information about the nature and absolute magnitude of outcomes, preventing learning about the longer-term value structure of the environment. Here we investigate the degree of adaptation in outcome coding brain regions in humans, for directly experienced outcomes and observed outcomes. We scanned participants while they performed a social learning task in gain and loss blocks. Multivariate pattern analysis showed two distinct networks of brain regions adapt to the most likely outcomes within a block. Frontostriatal areas adapted to directly experienced outcomes, whereas lateral frontal and temporoparietal regions adapted to observed social outcomes. Critically, in both cases, adaptation was incomplete and information about whether the outcomes arose in a gain block or a loss block was retained. Univariate analysis confirmed incomplete adaptive coding in these regions but also detected nonadapting outcome signals. Thus, although neural areas rescale their responses to outcomes for efficient coding, they adapt incompletely and keep track of the longer-term incentives available in the environment. SIGNIFICANCE STATEMENT Optimal value-based choice requires that the brain precisely and efficiently represents positive and negative outcomes. One way to increase efficiency is to adapt responding to the most likely outcomes in a given context. However, too strong adaptation would result in loss of precise representation (e.g., when the avoidance of a loss in a loss-context is coded the same as receipt of a gain in a gain-context). We investigated an intermediate form of adaptation that is efficient while maintaining information about received gains and avoided losses. We found that frontostriatal areas adapted to directly experienced outcomes, whereas lateral frontal and temporoparietal regions adapted to observed social outcomes. Importantly, adaptation was intermediate, in line with influential models of reference dependence in behavioral economics. PMID:27683899
Parallel heterogeneous architectures for efficient OMP compressive sensing reconstruction
NASA Astrophysics Data System (ADS)
Kulkarni, Amey; Stanislaus, Jerome L.; Mohsenin, Tinoosh
2014-05-01
Compressive Sensing (CS) is a novel scheme, in which a signal that is sparse in a known transform domain can be reconstructed using fewer samples. The signal reconstruction techniques are computationally intensive and have sluggish performance, which make them impractical for real-time processing applications . The paper presents novel architectures for Orthogonal Matching Pursuit algorithm, one of the popular CS reconstruction algorithms. We show the implementation results of proposed architectures on FPGA, ASIC and on a custom many-core platform. For FPGA and ASIC implementation, a novel thresholding method is used to reduce the processing time for the optimization problem by at least 25%. Whereas, for the custom many-core platform, efficient parallelization techniques are applied, to reconstruct signals with variant signal lengths of N and sparsity of m. The algorithm is divided into three kernels. Each kernel is parallelized to reduce execution time, whereas efficient reuse of the matrix operators allows us to reduce area. Matrix operations are efficiently paralellized by taking advantage of blocked algorithms. For demonstration purpose, all architectures reconstruct a 256-length signal with maximum sparsity of 8 using 64 measurements. Implementation on Xilinx Virtex-5 FPGA, requires 27.14 μs to reconstruct the signal using basic OMP. Whereas, with thresholding method it requires 18 μs. ASIC implementation reconstructs the signal in 13 μs. However, our custom many-core, operating at 1.18 GHz, takes 18.28 μs to complete. Our results show that compared to the previous published work of the same algorithm and matrix size, proposed architectures for FPGA and ASIC implementations perform 1.3x and 1.8x respectively faster. Also, the proposed many-core implementation performs 3000x faster than the CPU and 2000x faster than the GPU.
Perszyk, Danielle R; Waxman, Sandra R
2016-08-01
Well before they understand their first words, infants have begun to link language and cognition. This link is initially broad: At 3months, listening to both human and nonhuman primate vocalizations supports infants' object categorization, a building block of cognition. But by 6months, the link has narrowed: Only human vocalizations support categorization. What mechanisms underlie this rapid tuning process? Here, we document the crucial role of infants' experience as infants tune this link to cognition. Merely exposing infants to nonhuman primate vocalizations permits them to preserve, rather than sever, the link between these signals and categorization. Exposing infants to backward speech-a signal that fails to support categorization in the first year of life-does not have this advantage. This new evidence illuminates the central role of early experience as infants specify which signals, from an initially broad set, they will continue to link to core cognitive capacities. Copyright © 2016 Elsevier B.V. All rights reserved.
Interference in Bacterial Quorum Sensing: A Biopharmaceutical Perspective
Rémy, Benjamin; Mion, Sonia; Plener, Laure; Elias, Mikael; Chabrière, Eric; Daudé, David
2018-01-01
Numerous bacteria utilize molecular communication systems referred to as quorum sensing (QS) to synchronize the expression of certain genes regulating, among other aspects, the expression of virulence factors and the synthesis of biofilm. To achieve this process, bacteria use signaling molecules, known as autoinducers (AIs), as chemical messengers to share information. Naturally occurring strategies that interfere with bacterial signaling have been extensively studied in recent years, examining their potential to control bacteria. To interfere with QS, bacteria use quorum sensing inhibitors (QSIs) to block the action of AIs and quorum quenching (QQ) enzymes to degrade signaling molecules. Recent studies have shown that these strategies are promising routes to decrease bacterial pathogenicity and decrease biofilms, potentially enhancing bacterial susceptibility to antimicrobial agents including antibiotics and bacteriophages. The efficacy of QSIs and QQ enzymes has been demonstrated in various animal models and are now considered in the development of new medical devices against bacterial infections, including dressings, and catheters for enlarging the therapeutic arsenal against bacteria. PMID:29563876
Salicin, an extract from white willow bark, inhibits angiogenesis by blocking the ROS-ERK pathways.
Kong, Chang-Seok; Kim, Ka-Hyun; Choi, Jae-Sun; Kim, Ja-Eun; Park, Chan; Jeong, Joo-Won
2014-08-01
Salicin has been studied as a potent antiinflammatory agent. Angiogenesis is an essential process for tumor progression, and negative regulation of angiogenesis provides a good strategy for antitumor therapy. However, the potential medicinal value of salicin on antitumorigenic and antiangiogenic effects remain unexplored. In this study, we examined the antitumorigenic and antiangiogenic activity of salicin and its underlying mechanism of action. Salicin suppressed the angiogenic activity of endothelial cells, such as migration, tube formation, and sprouting from an aorta. Moreover, salicin reduced reactive oxygen species production and activation of the extracellular signal-regulated kinase pathway. The expression of vascular endothelial growth factor was also decreased by salicin in endothelial cells. When the salicin was administered to mice, salicin inhibited tumor growth and angiogenesis in a mouse tumor model. Taken together, salicin targets the signaling pathways mediated by reactive oxygen species and extracellular signal-regulated kinase, providing new perspectives into a potent therapeutic agent for hypervascularized tumors. Copyright © 2014 John Wiley & Sons, Ltd.
Zen, Ke; Guo, Yalan; Bian, Zhen; Lv, Zhiyuan; Zhu, Dihan; Ohnishi, Hiroshi; Matozaki, Takashi; Liu, Yuan
2018-01-01
Signal regulatory protein α (SIRPα), an immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptor, is an essential negative regulator of leukocyte inflammatory responses. Here we report that SIRPα cytoplasmic signalling ITIMs in neutrophils are cleaved during active inflammation and that the loss of SIRPα ITIMs enhances the polymorphonuclear leukocyte (PMN) inflammatory response. Using human leukocytes and two inflammatory models in mice, we show that the cleavage of SIRPα ITIMs in PMNs but not monocytes occurs at the post-acute stage of inflammation and correlates with increased PMN recruitment to inflammatory loci. Enhanced transmigration of PMNs and PMN-associated tissue damage are confirmed in mutant mice expressing SIRPα but lacking the ITIMs. Moreover, the loss of SIRPα ITIMs in PMNs during colitis is blocked by an anti-interleukin-17 (IL-17) antibody. These results demonstrate a SIRPα-based mechanism that dynamically regulates PMN inflammatory responses by generating a CD47-binding but non-signalling SIRPα ‘decoy’. PMID:24026300
Adenosine signaling promotes hematopoietic stem and progenitor cell emergence
Jing, Lili; Tamplin, Owen J.; Chen, Michael J.; Deng, Qing; Patterson, Shenia; Kim, Peter G.; Durand, Ellen M.; McNeil, Ashley; Green, Julie M.; Matsuura, Shinobu; Ablain, Julien; Brandt, Margot K.; Schlaeger, Thorsten M.; Huttenlocher, Anna; Daley, George Q.; Ravid, Katya
2015-01-01
Hematopoietic stem cells (HSCs) emerge from aortic endothelium via the endothelial-to-hematopoietic transition (EHT). The molecular mechanisms that initiate and regulate EHT remain poorly understood. Here, we show that adenosine signaling regulates hematopoietic stem and progenitor cell (HSPC) development in zebrafish embryos. The adenosine receptor A2b is expressed in the vascular endothelium before HSPC emergence. Elevated adenosine levels increased runx1+/cmyb+ HSPCs in the dorsal aorta, whereas blocking the adenosine pathway decreased HSPCs. Knockdown of A2b adenosine receptor disrupted scl+ hemogenic vascular endothelium and the subsequent EHT process. A2b adenosine receptor activation induced CXCL8 via cAMP–protein kinase A (PKA) and mediated hematopoiesis. We further show that adenosine increased multipotent progenitors in a mouse embryonic stem cell colony-forming assay and in embryonic day 10.5 aorta-gonad-mesonephros explants. Our results demonstrate that adenosine signaling plays an evolutionary conserved role in the first steps of HSPC formation in vertebrates. PMID:25870200
Power estimation on functional level for programmable processors
NASA Astrophysics Data System (ADS)
Schneider, M.; Blume, H.; Noll, T. G.
2004-05-01
In diesem Beitrag werden verschiedene Ansätze zur Verlustleistungsschätzung von programmierbaren Prozessoren vorgestellt und bezüglich ihrer Übertragbarkeit auf moderne Prozessor-Architekturen wie beispielsweise Very Long Instruction Word (VLIW)-Architekturen bewertet. Besonderes Augenmerk liegt hierbei auf dem Konzept der sogenannten Functional-Level Power Analysis (FLPA). Dieser Ansatz basiert auf der Einteilung der Prozessor-Architektur in funktionale Blöcke wie beispielsweise Processing-Unit, Clock-Netzwerk, interner Speicher und andere. Die Verlustleistungsaufnahme dieser Bl¨ocke wird parameterabhängig durch arithmetische Modellfunktionen beschrieben. Durch automatisierte Analyse von Assemblercodes des zu schätzenden Systems mittels eines Parsers können die Eingangsparameter wie beispielsweise der erzielte Parallelitätsgrad oder die Art des Speicherzugriffs gewonnen werden. Dieser Ansatz wird am Beispiel zweier moderner digitaler Signalprozessoren durch eine Vielzahl von Basis-Algorithmen der digitalen Signalverarbeitung evaluiert. Die ermittelten Schätzwerte für die einzelnen Algorithmen werden dabei mit physikalisch gemessenen Werten verglichen. Es ergibt sich ein sehr kleiner maximaler Schätzfehler von 3%. In this contribution different approaches for power estimation for programmable processors are presented and evaluated concerning their capability to be applied to modern digital signal processor architectures like e.g. Very Long InstructionWord (VLIW) -architectures. Special emphasis will be laid on the concept of so-called Functional-Level Power Analysis (FLPA). This approach is based on the separation of the processor architecture into functional blocks like e.g. processing unit, clock network, internal memory and others. The power consumption of these blocks is described by parameter dependent arithmetic model functions. By application of a parser based automized analysis of assembler codes of the systems to be estimated the input parameters of the Correspondence to: H. Blume (blume@eecs.rwth-aachen.de) arithmetic functions like e.g. the achieved degree of parallelism or the kind and number of memory accesses can be computed. This approach is exemplarily demonstrated and evaluated applying two modern digital signal processors and a variety of basic algorithms of digital signal processing. The resulting estimation values for the inspected algorithms are compared to physically measured values. A resulting maximum estimation error of 3% is achieved.
Boulanger, Ana; Farge, Morgane; Ramanoudjame, Christophe; Wharton, Kristi; Dura, Jean-Maurice
2012-01-01
Larval motor neurons remodel during Drosophila neuro-muscular junction dismantling at metamorphosis. In this study, we describe the motor neuron retraction as opposed to degeneration based on the early disappearance of β-Spectrin and the continuing presence of Tubulin. By blocking cell dynamics with a dominant-negative form of Dynamin, we show that phagocytes have a key role in this process. Importantly, we show the presence of peripheral glial cells close to the neuro-muscular junction that retracts before the motor neuron. We show also that in muscle, expression of EcR-B1 encoding the steroid hormone receptor required for postsynaptic dismantling, is under the control of the ftz-f1/Hr39 orphan nuclear receptor pathway but not the TGF-β signaling pathway. In the motor neuron, activation of EcR-B1 expression by the two parallel pathways (TGF-β signaling and nuclear receptor) triggers axon retraction. We propose that a signal from a TGF-β family ligand is produced by the dismantling muscle (postsynapse compartment) and received by the motor neuron (presynaptic compartment) resulting in motor neuron retraction. The requirement of the two pathways in the motor neuron provides a molecular explanation for the instructive role of the postsynapse degradation on motor neuron retraction. This mechanism insures the temporality of the two processes and prevents motor neuron pruning before postsynaptic degradation.
VHSIC Hardware Description Language (VHDL) Benchmark Suite
1990-10-01
T7 prit.iy label iTM Architecture label I flO inch Label I TIC ) P rae s Label I W Conkgurstion Spec. 1 21 Appendix B. Test Descriptions, Shell Code...Siensls R Accnss Operaist s Iov (soc 3 3 & 7 3 61 $ File I/0 S1 Reed S2 Write T Label Site TI Signal TIA Archi~ecture TIE Block TIC Port T2 VariableI...Access Operations I (sec 3 3 & 7.3 61 1 S FI I/0 1 Sl Read 52 Write T Label SreI TI Signal TIA Architeclt TIR Block TIC
LIF-activated Jak signaling determines Esrrb expression during late-stage reprogramming
Huang, Delun; Wang, Ling; Duan, Jingyue; Huang, Chang; Tian, Xiuchun (Cindy); Zhang, Ming
2018-01-01
ABSTRACT The regulatory process of naïve-state induced pluripotent stem cell (iPSC) generation is not well understood. Leukemia inhibitory factor (LIF)-activated Janus kinase/signal transducer and activator of transcription 3 (Jak/Stat3) is the master regulator for naïve-state pluripotency achievement and maintenance. The estrogen-related receptor beta (Esrrb) serves as a naïve-state marker gene regulating self-renewal of embryonic stem cells (ESCs). However, the interconnection between Esrrb and LIF signaling for pluripotency establishment in reprogramming is unclear. We screened the marker genes critical for complete reprogramming during mouse iPSC generation, and identified genes including Esrrb that are responsive to LIF/Jak pathway signaling. Overexpression of Esrrb resumes the reprogramming halted by inhibition of Jak activity in partially reprogrammed cells (pre-iPSCs), and leads to the generation of pluripotent iPSCs. We further show that neither overexpression of Nanog nor stimulation of Wnt signaling, two upstream regulators of Esrrb in ESCs, stimulates the expression of Esrrb in reprogramming when LIF or Jak activity is blocked. Our study demonstrates that Esrrb is a specific reprogramming factor regulated downstream of the LIF/Jak signaling pathway. These results shed new light on the regulatory role of LIF pathway on complete pluripotency establishment during iPSC generation. PMID:29212799
Ras promotes cell survival by antagonizing both JNK and Hid signals in the Drosophila eye.
Wu, Yue; Zhuang, Yuan; Han, Min; Xu, Tian; Deng, Kejing
2009-10-20
Programmed cell death, or apoptosis, is a fundamental physiological process during normal development or in pathological conditions. The activation of apoptosis can be elicited by numerous signalling pathways. Ras is known to mediate anti-apoptotic signals by inhibiting Hid activity in the Drosophila eye. Here we report the isolation of a new loss-of-function ras allele, rasKP, which causes excessive apoptosis in the Drosophila eye. This new function is likely to be mediated through the JNK pathway since the inhibition of JNK signalling can significantly suppress rasKP-induced apoptosis, whereas the removal of hid only weakly suppresses the phenotype. Furthermore, the reduction of JNK signalling together with the expression of the baculovirus caspase inhibitor p35, which blocks Hid activity, strongly suppresses the rasKP cell death. In addition, we find a strong correlation between rasKP-induced apoptosis in the eye disc and the activation of JNK signalling. In the Drosophila eye, Ras may protect cells from apoptosis by inhibiting both JNK and Hid activities. Surprisingly, reducing Ras activity in the wing, however, does not cause apoptosis but rather affects cell and organ size. Thus, in addition to its requirement for cell viability, Ras appears to mediate different biological roles depending on the developmental context and on the level of its expression.
Oschmann, Franziska; Mergenthaler, Konstantin; Jungnickel, Evelyn; Obermayer, Klaus
2017-02-01
Astrocytes integrate and process synaptic information and exhibit calcium (Ca2+) signals in response to incoming information from neighboring synapses. The generation of Ca2+ signals is mostly attributed to Ca2+ release from internal Ca2+ stores evoked by an elevated metabotropic glutamate receptor (mGluR) activity. Different experimental results associated the generation of Ca2+ signals to the activity of the glutamate transporter (GluT). The GluT itself does not influence the intracellular Ca2+ concentration, but it indirectly activates Ca2+ entry over the membrane. A closer look into Ca2+ signaling in different astrocytic compartments revealed a spatial separation of those two pathways. Ca2+ signals in the soma are mainly generated by Ca2+ release from internal Ca2+ stores (mGluR-dependent pathway). In astrocytic compartments close to the synapse most Ca2+ signals are evoked by Ca2+ entry over the plasma membrane (GluT-dependent pathway). This assumption is supported by the finding, that the volume ratio between the internal Ca2+ store and the intracellular space decreases from the soma towards the synapse. We extended a model for mGluR-dependent Ca2+ signals in astrocytes with the GluT-dependent pathway. Additionally, we included the volume ratio between the internal Ca2+ store and the intracellular compartment into the model in order to analyze Ca2+ signals either in the soma or close to the synapse. Our model results confirm the spatial separation of the mGluR- and GluT-dependent pathways along the astrocytic process. The model allows to study the binary Ca2+ response during a block of either of both pathways. Moreover, the model contributes to a better understanding of the impact of channel densities on the interaction of both pathways and on the Ca2+ signal.
Development of ROACH firmware for microwave multiplexed X-ray TES microcalorimeters
DOE Office of Scientific and Technical Information (OSTI.GOV)
Madden, T. J.; Cecil, T. W.; Gades, L. M.
We are developing room temperature electronics based upon the ROACH platform for reading out microwave multiplexed X-ray TES. ROACH is an open-source hardware and software platform featuring a large Xilinx Field Programmable Gate Array (FPGA), Power PC processor, several 10GB Ethernet SFP+ interfaces, and a collection of daughter boards for analog signal generation and acquisition. The combination of a ROACH board, ADC/DAC conversion daughter boards, and hardware for RF mixing allows for the generation and capture of multiple RF tones for reading out microwave multiplexed x-ray TES microcalorimeters. The FPGA is used to generate multiple tones in base band, frommore » 10MHz to 250MHz, which are subsequently mixed to RF in the multiple GHz range and sent through the microwave multiplexer. The tones are generated in the FPGA by storing a large lookup table in Quad Data Rate (QDR) SRAM modules and playing out the waveform to a DAC board. Once the signal has been modulated to RF, passed through the microwave multiplexer, and has been modulated back to base band, the signal is digitized by an ADC board. The tones are modulated to 0Hz by using a FPGA circuit consisting of a polyphase filter bank, several Xilinx FFT blocks, Xilinx CORDIC blocks (for converting to magnitude and phase), and special phase accumulator circuit for mixing to exactly 0Hz. Upwards of 256 channels can be simultaneously captured and written into a bank of 256 First-In-First-Out (FIFO) memories, with each FIFO corresponding to a channel. Individual channel data can be further processed in the FPGA before being streamed through a 10GB Ethernet fiber-optic interface to a Linux system. The Linux system runs software written in Python and QT C++ for controlling the ROACH system, capturing data, and processing data.« less
Therapeutic targeting of NOTCH1 signaling in T-ALL
Palomero, Teresa; Ferrando, Adolfo
2010-01-01
The recent identification of activating mutations in NOTCH1 in the majority of T-cell acute lymphoblastic leukemias (T-ALL) has brought major interest towards targeting the NOTCH signaling pathway in this disease. Small molecule γ-secretase inhibitors (GSIs) which block a critical proteolytic step required for NOTCH1 activation can effectively block the activity of NOTCH1 mutant alleles. However, the clinical development of GSIs has been hampered by their low cytotoxicity against human T-ALL and the development of significant gastrointestinal toxicity derived from inhibition of NOTCH signaling in the gut. Improved understanding of the oncogenic mechanisms of NOTCH1 and the effects of NOTCH inhibition in leukemic cells and the intestinal epithelium are required for the design of effective anti-NOTCH1 therapies in T-ALL. PMID:19778842
2010-01-01
Background Sexual selection theory predicts that females, being the limiting sex, invest less in courtship signals than males. However, when chemical signals are involved it is often the female that initiates mating by producing stimuli that inform about sex and/or receptivity. This apparent contradiction has been discussed in the literature as 'the female pheromone fallacy'. Because the release of chemical stimuli may not have evolved to elicit the male's courtship response, whether these female stimuli represent signals remains an open question. Using techniques to visualise and block release of urine, we studied the role of urine signals during fighting and mating interactions of crayfish (Pacifastacus leniusculus). Test individuals were blindfolded to exclude visual disturbance from dye release and artificial urine introduction. Results Staged female-male pairings during the reproductive season often resulted in male mating attempts. Blocking female urine release in such pairings prevented any male courtship behaviour. Artificial introduction of female urine re-established male mating attempts. Urine visualisation showed that female urine release coincides with aggressive behaviours but not with female submissive behaviour in reproductive interactions as well as in intersexual and intrasexual fights. In reproductive interactions, females predominately released urine during precopulatory aggression; males subsequently released significantly less urine during mating than in fights. Conclusions Urine-blocking experiments demonstrate that female urine contains sex-specific components that elicit male mating behaviour. The coincidence of chemical signalling and aggressive behaviour in both females and males suggests that urine release has evolved as an aggressive signal in both sexes of crayfish. By limiting urine release to aggressive behaviours in reproductive interactions females challenge their potential mating partners at the same time as they trigger a sexual response. These double messages should favour stronger males that are able to overcome the resistance of the female. We conclude that the difference between the sexes in disclosing urine-borne information reflects their conflicting interests in reproduction. Males discontinue aggressive urine signalling in order to increase their chances of mating. Females resume urine signalling in connection with aggressive behaviour, potentially repelling low quality or sexually inactive males while favouring reproduction with high quality males. PMID:20353555
Update on Bayesian Blocks: Segmented Models for Sequential Data
NASA Technical Reports Server (NTRS)
Scargle, Jeff
2017-01-01
The Bayesian Block algorithm, in wide use in astronomy and other areas, has been improved in several ways. The model for block shape has been generalized to include other than constant signal rate - e.g., linear, exponential, or other parametric models. In addition the computational efficiency has been improved, so that instead of O(N**2) the basic algorithm is O(N) in most cases. Other improvements in the theory and application of segmented representations will be described.
Kacprzyk, Joanna; Brogan, Niall P; Daly, Cara T; Doyle, Siamsa M; Diamond, Mark; Molony, Elizabeth M; McCabe, Paul F
2017-07-01
The protoplast retracts during apoptosis-like programmed cell death (AL-PCD) and, if this retraction is an active component of AL-PCD, it should be used as a defining feature for this type of programmed cell death. We used an array of pharmacological and genetic tools to test if the rates of protoplast retraction in cells undergoing AL-PCD can be modulated. Disturbing calcium flux signalling, ATP synthesis and mitochondrial permeability transition all inhibited protoplast retraction and often also the execution of the death programme. Protoplast retraction can precede loss of plasma membrane integrity and cell death can be interrupted after the protoplast retraction had already occurred. Blocking calcium influx inhibited the protoplast retraction, reduced DNA fragmentation and delayed death induced by AL-PCD associated stresses. At higher levels of stress, where cell death occurs without protoplast retraction, blocking calcium flux had no effect on the death process. The results therefore strongly suggest that retraction of the protoplast is an active biological process dependent on an early Ca 2+ -mediated trigger rather than cellular disintegration due to plasma membrane damage. Therefore this morphologically distinct cell type is a quantifiable feature, and consequently, reporter of AL-PCD. Copyright © 2017 Elsevier B.V. All rights reserved.
Externalizing proneness and brain response during pre-cuing and viewing of emotional pictures
Foell, Jens; Brislin, Sarah J.; Strickland, Casey M.; Seo, Dongju; Sabatinelli, Dean
2016-01-01
Externalizing proneness, or trait disinhibition, is a concept relevant to multiple high-impact disorders involving impulsive-aggressive behavior. Its mechanisms remain disputed: major models posit hyperresponsive reward circuitry or heightened threat-system reactivity as sources of disinhibitory tendencies. This study evaluated alternative possibilities by examining relations between trait disinhibition and brain reactivity during preparation for and processing of visual affective stimuli. Forty females participated in a functional neuroimaging procedure with stimuli presented in blocks containing either pleasurable or aversive pictures interspersed with neutral, with each picture preceded by a preparation signal. Preparing to view elicited activation in regions including nucleus accumbens, whereas visual regions and bilateral amygdala were activated during viewing of emotional pictures. High disinhibition predicted reduced nucleus accumbens activation during preparation within pleasant/neutral picture blocks, along with enhanced amygdala reactivity during viewing of pleasant and aversive pictures. Follow-up analyses revealed that the augmented amygdala response was related to reduced preparatory activation. Findings indicate that participants high in disinhibition are less able to process implicit cues and mentally prepare for upcoming stimuli, leading to limbic hyperreactivity during processing of actual stimuli. This outcome is helpful for integrating findings from studies suggesting reward-system hyperreactivity and others suggesting threat-system hyperreactivity as mechanisms for externalizing proneness. PMID:26113614
Narayanan, Shrikanth; Georgiou, Panayiotis G
2013-02-07
The expression and experience of human behavior are complex and multimodal and characterized by individual and contextual heterogeneity and variability. Speech and spoken language communication cues offer an important means for measuring and modeling human behavior. Observational research and practice across a variety of domains from commerce to healthcare rely on speech- and language-based informatics for crucial assessment and diagnostic information and for planning and tracking response to an intervention. In this paper, we describe some of the opportunities as well as emerging methodologies and applications of human behavioral signal processing (BSP) technology and algorithms for quantitatively understanding and modeling typical, atypical, and distressed human behavior with a specific focus on speech- and language-based communicative, affective, and social behavior. We describe the three important BSP components of acquiring behavioral data in an ecologically valid manner across laboratory to real-world settings, extracting and analyzing behavioral cues from measured data, and developing models offering predictive and decision-making support. We highlight both the foundational speech and language processing building blocks as well as the novel processing and modeling opportunities. Using examples drawn from specific real-world applications ranging from literacy assessment and autism diagnostics to psychotherapy for addiction and marital well being, we illustrate behavioral informatics applications of these signal processing techniques that contribute to quantifying higher level, often subjectively described, human behavior in a domain-sensitive fashion.
Downregulation of Ras C-terminal processing by JNK inhibition
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mouri, Wataru; Department of Neurosurgery, Yamagata University School of Medicine, Yamagata 990-9585; Biology Division, National Cancer Center Research Institute, Tokyo 104-0045
2008-06-27
After translation, Ras proteins undergo a series of modifications at their C-termini. This post-translational C-terminal processing is essential for Ras to become functional, but it remains unknown whether and how Ras C-terminal processing is regulated. Here we show that the C-terminal processing and subsequent plasma membrane localization of H-Ras as well as the activation of the downstream signaling pathways by H-Ras are prevented by JNK inhibition. Conversely, JNK activation by ultraviolet irradiation resulted in promotion of C-terminal processing of H-Ras. Furthermore, increased cell density promoted C-terminal processing of H-Ras most likely through an autocrine/paracrine mechanism, which was also blocked undermore » JNK-inhibited condition. Ras C-terminal processing was sensitive to JNK inhibition in the case of H- and N-Ras but not K-Ras, and in a variety of cell types. Thus, our results suggest for the first time that Ras C-terminal processing is a regulated mechanism in which JNK is involved.« less
Waring, D A; Kenyon, C
1991-04-25
In Caenorhabditis elegans, cell-cell communication is required to form a simple pattern of sensory ray neurons and cuticular structures (alae). The C. elegans pal-1 gene initiates one developmental pathway (ray lineages) simply by blocking a cell-cell interaction that induces an alternative pathway. Here we show by mosaic analysis that pal-1+ acts by preventing specific cells from responding to inductive signals. The results indicate that although cell signals play a critical role in generating this pattern, they do not provide spatial information. Instead, signals are sent to many, if not all, of the precursor cells, and the ability to respond is spatially restricted. This patterning strategy thus differs from many well known models for pattern formation in which localized inductive signals influence a subset of cells within a field. We find that pal-1 encodes a homeodomain protein and so is likely to regulate transcription. The pal-1+ protein could block the response to cell signals either by repressing genes involved in signal transduction or by acting directly on downstream genes in a way that neutralizes the effects of the intercellular signals. Genetic experiments indicate that one candidate for such a downstream gene is the Antennapedia-like homeotic selector gene mab-5.
A concept to standardize raw biosignal transmission for brain-computer interfaces.
Breitwieser, Christian; Neuper, Christa; Müller-Putz, Gernot R
2011-01-01
With this concept we introduced the attempt of a standardized interface called TiA to transmit raw biosignals. TiA is able to deal with multirate and block-oriented data transmission. Data is distinguished by different signal types (e.g., EEG, EOG, NIRS, …), whereby those signals can be acquired at the same time from different acquisition devices. TiA is built as a client-server model. Multiple clients can connect to one server. Information is exchanged via a control- and a separated data connection. Control commands and meta information are transmitted over the control connection. Raw biosignal data is delivered using the data connection in a unidirectional way. For this purpose a standardized handshaking protocol and raw data packet have been developed. Thus, an abstraction layer between hardware devices and data processing was evolved facilitating standardization.
Arikan and Alamouti matrices based on fast block-wise inverse Jacket transform
NASA Astrophysics Data System (ADS)
Lee, Moon Ho; Khan, Md Hashem Ali; Kim, Kyeong Jin
2013-12-01
Recently, Lee and Hou (IEEE Signal Process Lett 13: 461-464, 2006) proposed one-dimensional and two-dimensional fast algorithms for block-wise inverse Jacket transforms (BIJTs). Their BIJTs are not real inverse Jacket transforms from mathematical point of view because their inverses do not satisfy the usual condition, i.e., the multiplication of a matrix with its inverse matrix is not equal to the identity matrix. Therefore, we mathematically propose a fast block-wise inverse Jacket transform of orders N = 2 k , 3 k , 5 k , and 6 k , where k is a positive integer. Based on the Kronecker product of the successive lower order Jacket matrices and the basis matrix, the fast algorithms for realizing these transforms are obtained. Due to the simple inverse and fast algorithms of Arikan polar binary and Alamouti multiple-input multiple-output (MIMO) non-binary matrices, which are obtained from BIJTs, they can be applied in areas such as 3GPP physical layer for ultra mobile broadband permutation matrices design, first-order q-ary Reed-Muller code design, diagonal channel design, diagonal subchannel decompose for interference alignment, and 4G MIMO long-term evolution Alamouti precoding design.
Complex capacitance in the representation of modulus of the lithium niobate crystals
NASA Astrophysics Data System (ADS)
Alim, Mohammad A.; Batra, A. K.; Bhattacharjee, Sudip; Aggarwal, M. D.
2011-03-01
The lithium niobate (LiNbO 3 or LN) single crystal is grown in-house. The ac small-signal electrical characterization is conducted over a temperature range 35 ≤T≤150 °C as a function of measurement frequency (10 ≤f≤10 6 Hz). Meaningful observation is noted only in a narrow temperature range 59 ≤T≤73 °C. These electrical data when analyzed via complex plane formalisms revealed single semicircular relaxation both in the complex capacitance ( C*) and in the modulus ( M*) planes. The physical meaning of this kind of observation is obtained on identifying the relaxation type, and then incorporating respective equivalent circuit model. The simplistic non-blocking nature of the equivalent circuit model obtained via M*-plane is established as the lumped relaxation is identified in the C*-plane. The feature of the eventual equivalent circuit model allows non-blocking aspect for the LN crystal attributing to the presence of the operative dc conduction process. Identification of this leakage dc conduction via C*-plane is portrayed in the M*-plane where the blocking nature is removed. The interacting interpretation between these two complex planes is successfully presented.
Decision Criterion Dynamics in Animals Performing an Auditory Detection Task
Mill, Robert W.; Alves-Pinto, Ana; Sumner, Christian J.
2014-01-01
Classical signal detection theory attributes bias in perceptual decisions to a threshold criterion, against which sensory excitation is compared. The optimal criterion setting depends on the signal level, which may vary over time, and about which the subject is naïve. Consequently, the subject must optimise its threshold by responding appropriately to feedback. Here a series of experiments was conducted, and a computational model applied, to determine how the decision bias of the ferret in an auditory signal detection task tracks changes in the stimulus level. The time scales of criterion dynamics were investigated by means of a yes-no signal-in-noise detection task, in which trials were grouped into blocks that alternately contained easy- and hard-to-detect signals. The responses of the ferrets implied both long- and short-term criterion dynamics. The animals exhibited a bias in favour of responding “yes” during blocks of harder trials, and vice versa. Moreover, the outcome of each single trial had a strong influence on the decision at the next trial. We demonstrate that the single-trial and block-level changes in bias are a manifestation of the same criterion update policy by fitting a model, in which the criterion is shifted by fixed amounts according to the outcome of the previous trial and decays strongly towards a resting value. The apparent block-level stabilisation of bias arises as the probabilities of outcomes and shifts on single trials mutually interact to establish equilibrium. To gain an intuition into how stable criterion distributions arise from specific parameter sets we develop a Markov model which accounts for the dynamic effects of criterion shifts. Our approach provides a framework for investigating the dynamics of decisions at different timescales in other species (e.g., humans) and in other psychological domains (e.g., vision, memory). PMID:25485733
SU-E-I-08: Investigation of Deconvolution Methods for Blocker-Based CBCT Scatter Estimation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhao, C; Jin, M; Ouyang, L
2015-06-15
Purpose: To investigate whether deconvolution methods can improve the scatter estimation under different blurring and noise conditions for blocker-based scatter correction methods for cone-beam X-ray computed tomography (CBCT). Methods: An “ideal” projection image with scatter was first simulated for blocker-based CBCT data acquisition by assuming no blurring effect and no noise. The ideal image was then convolved with long-tail point spread functions (PSF) with different widths to mimic the blurring effect from the finite focal spot and detector response. Different levels of noise were also added. Three deconvolution Methods: 1) inverse filtering; 2) Wiener; and 3) Richardson-Lucy, were used tomore » recover the scatter signal in the blocked region. The root mean square error (RMSE) of estimated scatter serves as a quantitative measure for the performance of different methods under different blurring and noise conditions. Results: Due to the blurring effect, the scatter signal in the blocked region is contaminated by the primary signal in the unblocked region. The direct use of the signal in the blocked region to estimate scatter (“direct method”) leads to large RMSE values, which increase with the increased width of PSF and increased noise. The inverse filtering is very sensitive to noise and practically useless. The Wiener and Richardson-Lucy deconvolution methods significantly improve scatter estimation compared to the direct method. For a typical medium PSF and medium noise condition, both methods (∼20 RMSE) can achieve 4-fold improvement over the direct method (∼80 RMSE). The Wiener method deals better with large noise and Richardson-Lucy works better on wide PSF. Conclusion: We investigated several deconvolution methods to recover the scatter signal in the blocked region for blocker-based scatter correction for CBCT. Our simulation results demonstrate that Wiener and Richardson-Lucy deconvolution can significantly improve the scatter estimation compared to the direct method.« less
Study of mathematical modeling of communication systems transponders and receivers
NASA Technical Reports Server (NTRS)
Walsh, J. R.
1972-01-01
The modeling of communication receivers is described at both the circuit detail level and at the block level. The largest effort was devoted to developing new models at the block modeling level. The available effort did not permit full development of all of the block modeling concepts envisioned, but idealized blocks were developed for signal sources, a variety of filters, limiters, amplifiers, mixers, and demodulators. These blocks were organized into an operational computer simulation of communications receiver circuits identified as the frequency and time circuit analysis technique (FATCAT). The simulation operates in both the time and frequency domains, and permits output plots or listings of either frequency spectra or time waveforms from any model block. Transfer between domains is handled with a fast Fourier transform algorithm.
49 CFR 236.1029 - PTC system use and en route failures.
Code of Federal Regulations, 2010 CFR
2010-10-01
... system component fails to perform its intended function, the cause must be determined and the faulty... advance of the train in accordance with the following: (i) Where no block signal system is in use, the... location where an absolute block has been established in advance of the train, as referenced in paragraph...
Context Blocking in Rat Autoshaping: Sign-Tracking versus Goal-Tracking
ERIC Educational Resources Information Center
Costa, Daniel S. J.; Boakes, Robert A.
2009-01-01
Prior experience of unsignaled food can interfere with subsequent acquisition by birds of autoshaped key-pecking at a signal light. This has been understood to indicate that unsignaled food results in context conditioning, which blocks subsequent learning about the keylight-food relationship. In the present experiment with rats lever insertion as…
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.
Miura, Shin-Ichiro; Suematsu, Yasunori; Matsuo, Yoshino; Tomita, Sayo; Nakayama, Asuka; Goto, Masaki; Arimura, Tadaaki; Kuwano, Takashi; Yahiro, Eiji; Saku, Keijiro
2016-11-01
A recent clinical study indicated that an angiotensin II (Ang II) type 1 (AT 1 ) receptor-neprilysin inhibitor (ARNi) designated LCZ696 (sacubitril/valsartan, as combined sodium complex) was superior to enalapril at reducing the risks of death and hospitalization due to heart failure. Therefore, we investigated the possible mechanisms of the beneficial effect of LCZ696, in which the inhibition of neprilysin enhances atrial natriuretic peptide (NP) or brain NP (ANP or BNP)-evoked signals that can block Ang II/AT 1 receptor-induced aldosterone (Ald) synthesis in human adrenocortical cells. The binding affinity of valsartan+LBQ657 (active moiety of sacubitril) to the AT 1 receptor was greater than that of valsartan alone in an AT 1 receptor-expressing human embryonic kidney cell-based assay. There was no difference in the dissociation from the AT 1 receptor between valsartan+LBQ657 and valsartan alone. In Ang II-sensitized human adrenocortical cells, ANP or BNP alone, but not LBQ657 or valsartan alone, significantly decreased Ald synthesis. The level of suppression of Ald synthesis by ANP or BNP with LBQ657 was greater than that by ANP or BNP without LBQ657. The suppression of ANP was blocked by inhibitors of regulator of G-protein signaling proteins and cyclic GMP-dependent protein kinase. The inhibition of neprilysin did not change the mRNA levels of the AT 1 receptor, ANP receptor A, regulator of G-protein signaling protein, renin or 3β-hydroxysteroid dehydrogenases. In conclusion, the inhibition of neprilysin by LBQ657 enhances the NP-evoked signals that can block Ang II/AT 1 receptor-induced Ald synthesis in human adrenocortical cells.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Dong Il; Park, Soo Hyun, E-mail: parksh@chonnam.ac.kr
Highlights: •The pathophysiological role of IL-6 in high glucose-induced podocyte loss. •The novel role of PGC-1α in the development of diabetic nephropathy. •Signaling of IL-6 and PGC-1α in high glucose-induced dysfunction of podocyte. -- Abstract: Podocyte loss, which is mediated by podocyte apoptosis, is implicated in the onset of diabetic nephropathy. In this study, we investigated the involvement of interleukin (IL)-6 in high glucose-induced apoptosis of rat podocytes. We also examined the pathophysiological role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) in this system. High glucose treatment induced not only podocyte apoptosis but also podocyte growth arrest. High glucosemore » treatment also increased IL-6 secretion and activated IL-6 signaling. The high glucose-induced podocyte apoptosis was blocked by IL-6 neutralizing antibody. IL-6 treatment or overexpression induced podocyte apoptosis and growth arrest, and IL-6 siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Furthermore, high glucose or IL-6 treatment increased PGC-1α expression, and PGC-1α overexpression also induced podocyte apoptosis and growth arrest. PGC-1α siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Collectively, these findings showed that high glucose promoted apoptosis and cell growth arrest in podocytes via IL-6 signaling. In addition, PGC-1α is involved in podocyte apoptosis and cell growth arrest. Therefore, blocking IL-6 and its downstream mediators such as IL6Rα, gp130 and PGC-1α may attenuate the progression of diabetic nephropathy.« less
Chang, Shang-Hung; Yeh, Yung-Hsin; Lee, Jia-Lin; Hsu, Yu-Juei; Kuo, Chi-Tai; Chen, Wei-Jan
2017-09-04
Atrial fibrillation (AF) is associated with atrial fibrosis. Inhibition of atrial fibrosis might be a plausible approach for AF prevention and therapy. This study is designed to evaluate the potential role of CD44, a membrane receptor known to regulate fibrosis, and its related signaling in the pathogenesis of atrial fibrosis and AF. Treatment of cultured rat atrial fibroblasts with transforming growth factor-β (TGF-β, a key mediator of atrial fibrosis) led to a higher expression of hyaluronan (HA), CD44, STAT3, and collagen (a principal marker of fibrosis) than that of ventricular fibroblasts. In vivo, TGF-β transgenic mice and AF patients exhibited a greater expression of HA, CD44, STAT3, and collagen in their atria than wild-type mice and sinus rhythm subjects, respectively. Treating TGF-β transgenic mice with an anti-CD44 blocking antibody resulted in a lower expression of STAT3 and collagen in their atria than those with control IgG antibody. Programmed stimulation triggered less AF episodes in TGF-β transgenic mice treated with anti-CD44 blocking antibody than in those with control IgG. Blocking CD44 signaling with anti-CD44 antibody and mutated CD44 plasmids attenuated TGF-β-induced STAT3 activation and collagen expression in cultured atrial fibroblasts. Deletion and mutational analysis of the collagen promoter along with chromatin immunoprecipitation demonstrated that STAT3 served as a vital transcription factor in collagen expression. TGF-β-mediated HA/CD44/STAT3 pathway plays a crucial role in the development of atrial fibrosis and AF. Blocking CD44-dependent signaling may be a feasible way for AF management.
Wheeler, David S.; Underhill, Suzanne M.; Stolz, Donna B.; Murdoch, Geoffrey H.; Thiels, Edda; Romero, Guillermo; Amara, Susan G.
2015-01-01
Acute amphetamine (AMPH) exposure elevates extracellular dopamine through a variety of mechanisms that include inhibition of dopamine reuptake, depletion of vesicular stores, and facilitation of dopamine efflux across the plasma membrane. Recent work has shown that the DAT substrate AMPH, unlike cocaine and other nontransported blockers, can also stimulate endocytosis of the plasma membrane dopamine transporter (DAT). Here, we show that when AMPH enters the cytoplasm it rapidly stimulates DAT internalization through a dynamin-dependent, clathrin-independent process. This effect, which can be observed in transfected cells, cultured dopamine neurons, and midbrain slices, is mediated by activation of the small GTPase RhoA. Inhibition of RhoA activity with C3 exotoxin or a dominant-negative RhoA blocks AMPH-induced DAT internalization. These actions depend on AMPH entry into the cell and are blocked by the DAT inhibitor cocaine. AMPH also stimulates cAMP accumulation and PKA-dependent inactivation of RhoA, thus providing a mechanism whereby PKA- and RhoA-dependent signaling pathways can interact to regulate the timing and robustness of AMPH’s effects on DAT internalization. Consistent with this model, the activation of D1/D5 receptors that couple to PKA in dopamine neurons antagonizes RhoA activation, DAT internalization, and hyperlocomotion observed in mice after AMPH treatment. These observations support the existence of an unanticipated intracellular target that mediates the effects of AMPH on RhoA and cAMP signaling and suggest new pathways to target to disrupt AMPH action. PMID:26553986
Disruption of Canonical TGFβ-signaling in Murine Coronary Progenitor Cells by Low Level Arsenic
Allison, Patrick; Huang, Tianfang; Broka, Derrick; Parker, Patti; Barnett, Joey V.; Camenisch, Todd D.
2013-01-01
Exposure to arsenic results in several types of cancers as well as heart disease. A major contributor to ischemic heart pathologies is coronary artery disease, however the influences by environmental arsenic in this disease process are not known. Similarly, the impact of toxicants on blood vessel formation and function during development has not been studied. During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types including smooth muscle cells which contribute to the coronary vessels. The TGFβ family of ligands and receptors are essential for developmental cardiac epithelial to mesenchymal transition (EMT) and differentiation into coronary smooth muscle cells. In this in vitrostudy, 18 hour exposure to 1.34 μMarsenite disrupted developmental EMT programming in murine epicardial cells causing a deficit in cardiac mesenchyme. The expression of EMT genes including TGFβ2, TGFβ receptor-3, Snail, and Has-2 are decreased in a dose-dependent manner following exposure to arsenite. TGFβ2 cell signaling is abrogated as detected by decreases in phosphorylated Smad2/3 when cells are exposed to 1.34 μMarsenite. There is also loss of nuclear accumulation pSmad due to arsenite exposure. These observations coincide with a decrease invimentinpositive mesenchymal cells invading three-dimensional collagen gels. However, arsenite does not block TGFβ2 mediated smooth muscle cell differentiation by epicardial cells. Overall these results show that arsenic exposure blocks developmental EMT gene programming in murine coronary progenitor cells by disrupting TGFβ2 signals and Smad activation, and that smooth muscle cell differentiation is refractory to this arsenic toxicity. PMID:23732083
Smooth muscle tension induces invasive remodeling of the zebrafish intestine.
Seiler, Christoph; Davuluri, Gangarao; Abrams, Joshua; Byfield, Fitzroy J; Janmey, Paul A; Pack, Michael
2012-01-01
The signals that initiate cell invasion are not well understood, but there is increasing evidence that extracellular physical signals play an important role. Here we show that epithelial cell invasion in the intestine of zebrafish meltdown (mlt) mutants arises in response to unregulated contractile tone in the surrounding smooth muscle cell layer. Physical signaling in mlt drives formation of membrane protrusions within the epithelium that resemble invadopodia, matrix-degrading protrusions present in invasive cancer cells. Knockdown of Tks5, a Src substrate that is required for invadopodia formation in mammalian cells blocked formation of the protrusions and rescued invasion in mlt. Activation of Src-signaling induced invadopodia-like protrusions in wild type epithelial cells, however the cells did not migrate into the tissue stroma, thus indicating that the protrusions were required but not sufficient for invasion in this in vivo model. Transcriptional profiling experiments showed that genes responsive to reactive oxygen species (ROS) were upregulated in mlt larvae. ROS generators induced invadopodia-like protrusions and invasion in heterozygous mlt larvae but had no effect in wild type larvae. Co-activation of oncogenic Ras and Wnt signaling enhanced the responsiveness of mlt heterozygotes to the ROS generators. These findings present the first direct evidence that invadopodia play a role in tissue cell invasion in vivo. In addition, they identify an inducible physical signaling pathway sensitive to redox and oncogenic signaling that can drive this process.
Smooth Muscle Tension Induces Invasive Remodeling of the Zebrafish Intestine
Seiler, Christoph; Davuluri, Gangarao; Abrams, Joshua; Byfield, Fitzroy J.; Janmey, Paul A.; Pack, Michael
2012-01-01
The signals that initiate cell invasion are not well understood, but there is increasing evidence that extracellular physical signals play an important role. Here we show that epithelial cell invasion in the intestine of zebrafish meltdown (mlt) mutants arises in response to unregulated contractile tone in the surrounding smooth muscle cell layer. Physical signaling in mlt drives formation of membrane protrusions within the epithelium that resemble invadopodia, matrix-degrading protrusions present in invasive cancer cells. Knockdown of Tks5, a Src substrate that is required for invadopodia formation in mammalian cells blocked formation of the protrusions and rescued invasion in mlt. Activation of Src-signaling induced invadopodia-like protrusions in wild type epithelial cells, however the cells did not migrate into the tissue stroma, thus indicating that the protrusions were required but not sufficient for invasion in this in vivo model. Transcriptional profiling experiments showed that genes responsive to reactive oxygen species (ROS) were upregulated in mlt larvae. ROS generators induced invadopodia-like protrusions and invasion in heterozygous mlt larvae but had no effect in wild type larvae. Co-activation of oncogenic Ras and Wnt signaling enhanced the responsiveness of mlt heterozygotes to the ROS generators. These findings present the first direct evidence that invadopodia play a role in tissue cell invasion in vivo. In addition, they identify an inducible physical signaling pathway sensitive to redox and oncogenic signaling that can drive this process. PMID:22973180
Llamas: Large-area microphone arrays and sensing systems
NASA Astrophysics Data System (ADS)
Sanz-Robinson, Josue
Large-area electronics (LAE) provides a platform to build sensing systems, based on distributing large numbers of densely spaced sensors over a physically-expansive space. Due to their flexible, "wallpaper-like" form factor, these systems can be seamlessly deployed in everyday spaces. They go beyond just supplying sensor readings, but rather they aim to transform the wealth of data from these sensors into actionable inferences about our physical environment. This requires vertically integrated systems that span the entirety of the signal processing chain, including transducers and devices, circuits, and signal processing algorithms. To this end we develop hybrid LAE / CMOS systems, which exploit the complementary strengths of LAE, enabling spatially distributed sensors, and CMOS ICs, providing computational capacity for signal processing. To explore the development of hybrid sensing systems, based on vertical integration across the signal processing chain, we focus on two main drivers: (1) thin-film diodes, and (2) microphone arrays for blind source separation: 1) Thin-film diodes are a key building block for many applications, such as RFID tags or power transfer over non-contact inductive links, which require rectifiers for AC-to-DC conversion. We developed hybrid amorphous / nanocrystalline silicon diodes, which are fabricated at low temperatures (<200 °C) to be compatible with processing on plastic, and have high current densities (5 A/cm2 at 1 V) and high frequency operation (cutoff frequency of 110 MHz). 2) We designed a system for separating the voices of multiple simultaneous speakers, which can ultimately be fed to a voice-command recognition engine for controlling electronic systems. On a device level, we developed flexible PVDF microphones, which were used to create a large-area microphone array. On a circuit level we developed localized a-Si TFT amplifiers, and a custom CMOS IC, for system control, sensor readout and digitization. On a signal processing level we developed an algorithm for blind source separation in a real, reverberant room, based on beamforming and binary masking. It requires no knowledge about the location of the speakers or microphones. Instead, it uses cluster analysis techniques to determine the time delays for beamforming; thus, adapting to the unique acoustic environment of the room.
Associative list processing unit
Hemmert, Karl Scott; Underwood, Keith D.
2013-01-29
An associative list processing unit and method comprising employing a plurality of prioritized cell blocks and permitting inserts to occur in a single clock cycle if all of the cell blocks are not full. Also, an associative list processing unit and method comprising employing a plurality of prioritized cell blocks and using a tree of prioritized multiplexers descending from the plurality of cell blocks.