Science.gov

Sample records for activating sonar signal

  1. Enhanced Multistatic Active Sonar via Innovative Signal Processing

    DTIC Science & Technology

    2015-09-30

    Grove, CA, November, 2014. [in press, refereed]. C . Gianelli, L. Xu, and J. Li, " Active Sonar Systems in the Presence of Strong Direct Blast", Oceans...3. DATES COVERED (From - To) Oct. 01, 2014-Sept. 30, 2015 4. TITLE AND SUBTITLE Enhanced Multistatic Active Sonar via Innovative Signal... active sonar (CAS) in the presence of strong direct blast is studied for the Doppler-tolerant linear frequency modulation waveform. A receiver design

  2. Enhanced Multistatic Active Sonar via Innovative Signal Processing

    DTIC Science & Technology

    2014-09-30

    DATES COVERED (From - To) Oct. 01. 2013-Sept. 30, 2014 4. TITLE AND SUBTITLE Enhanced Multistatic Active Sonar via Innovative Signal Processing 5a...DISTRIBUTION AVAILABILITY STATEMENT Approved for Public Release; Distribution is Unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT Pulsed active sonar ...PAS) and continuous active sonar (CAS) in the presence of strong direct blast are studied for the Doppler-tolerant linear frequency modulation

  3. Predicting the Environmental Impact of Active Sonar

    NASA Astrophysics Data System (ADS)

    Duncan, Alec J.; McCauley, Robert D.; Maggi, Amos L.

    2004-11-01

    The effect of active sonar on marine animals, particularly mammals, has become a hot topic in recent times. The Australian Environmental Protection and Biodiversity Conservation Act 1999 obligates Defence to avoid significant environmental impacts from Navy activities including those which produce underwater sound such as active sonar. It is in the interests of all parties that these effects be modeled accurately to facilitate both the quantitative evaluation of the consequences of any proposed sonar trials, and the identification of suitable mitigation procedures. This paper discusses the received signal parameters that are of importance when predicting the effect of sonar systems on marine animals and techniques for modeling both the expected values of these parameters and their statistical fluctuations.

  4. Digital sonar system

    DOEpatents

    Young, Kenneth K.; Wilkes, R. Jeffrey

    1995-01-01

    A transponder of an active digital sonar system identifies a multifrequency underwater activating sonar signal received from a remote sonar transmitter. The transponder includes a transducer that receives acoustic waves, including the activating sonar signal, and generates an analog electrical receipt signal. The analog electrical receipt signal is converted to a digital receipt signal and cross-correlated with a digital transmission signal pattern corresponding to the activating sonar signal. A relative peak in the cross-correlation value is indicative of the activating sonar signal having been received by the transponder. In response to identifying the activating sonar signal, the transponder transmits a responding multifrequency sonar signal.

  5. Digital sonar system

    DOEpatents

    Young, K.K.; Wilkes, R.J.

    1995-11-21

    A transponder of an active digital sonar system identifies a multifrequency underwater activating sonar signal received from a remote sonar transmitter. The transponder includes a transducer that receives acoustic waves, including the activating sonar signal, and generates an analog electrical receipt signal. The analog electrical receipt signal is converted to a digital receipt signal and cross-correlated with a digital transmission signal pattern corresponding to the activating sonar signal. A relative peak in the cross-correlation value is indicative of the activating sonar signal having been received by the transponder. In response to identifying the activating sonar signal, the transponder transmits a responding multifrequency sonar signal. 4 figs.

  6. Low Frequency Sonar Signal Simulation

    DTIC Science & Technology

    2010-04-14

    participating in workshops. Task 3, Assess SST Propagation Accuracy at Low Frequencies: Determine accuracy domain of SST eigenray -based propagation model at... eigenrays ). The new algorithm, which is conceptually similar to the “point scatterer” approach, generates uncorrelated random Gaussian scattering...amplitudes for many cells (smaller than the sonar resolution) covering the bottom. These are combined with eigenray pairs and weighted by the angle

  7. Environmentally associated signal-to-interference variability in low-frequency active sonar in Korea Strait

    NASA Astrophysics Data System (ADS)

    Cable, P. G.; Carey, W. M.

    2005-09-01

    An analysis has been conducted of spatial and temporal variability of target echo-to-interference measurements made during Area Characterization Test III (ACT III) in 1995 in the Korea Strait. The measurements were made over a 5-day period for five fixed bistatic geometries (spatial scale of order 200 square km) using explosive sources, bottom-mounted horizontal receiving hydrophone arrays, and passive reflector targets in 100-m-depth water under downward-refracting acoustic conditions. The bottom at the ACT III site was nearly flat, of sand-silt composition. Meteorological conditions were relatively calm over the conduction of the measurements, but the main proximate oceanographic feature, the South Korean Coastal Front, did result in a relatively varied and complex sound-speed environment. The signal-to-interference fluctuation statistics associated with a single ping was determined to give a standard deviation of order 1 dB, while the observed variability of signal-to-interference over the spatial and temporal scales of the measurements gave a standard deviation of about 2 dB. The observed variability of received signal-to-interference will be discussed in terms of physical causes and measurement error. [Work supported by ONR Code OA321.

  8. Trading detection for resolution in active sonar receivers.

    PubMed

    Sharma, Nabin S; Buck, John R; Simmons, James A

    2011-09-01

    This paper proposes an active sonar receivers that offers a smooth trade-off between detection and resolution. A matched filter is the optimal detector of known signals in white Gaussian noise but may fail to resolve the targets if the time separation of targets is less than the mainlobe width of the autocorrelation function of the transmitted signal. An inverse filter achieves optimal resolution performance for multiple targets in the absence of noise, but amplifies the noise outside the signal bandwidth in a manner that makes it impractical in many realistic scenarios. The proposed active sonar receiver, the variable resolution and detection receiver (VRDR) combines the matched and inverse filter properties to achieve a smooth trade-off between detection and resolution. Simulated receiver operating characteristics demonstrate that for a range of dipole sonar targets, the performance of the VRDR is superior to the matched and inverse filter, as well as another previously proposed bandlimited inverse filter.

  9. Novel sonar signal processing tool using Shannon entropy

    SciTech Connect

    Quazi, A.H.

    1996-06-01

    Traditionally, conventional signal processing extracts information from sonar signals using amplitude, signal energy or frequency domain quantities obtained using spectral analysis techniques. The object is to investigate an alternate approach which is entirely different than that of traditional signal processing. This alternate approach is to utilize the Shannon entropy as a tool for the processing of sonar signals with emphasis on detection, classification, and localization leading to superior sonar system performance. Traditionally, sonar signals are processed coherently, semi-coherently, and incoherently, depending upon the a priori knowledge of the signals and noise. Here, the detection, classification, and localization technique will be based on the concept of the entropy of the random process. Under a constant energy constraint, the entropy of a received process bearing finite number of sample points is maximum when hypothesis H{sub 0} (that the received process consists of noise alone) is true and decreases when correlated signal is present (H{sub 1}). Therefore, the strategy used for detection is: (I) Calculate the entropy of the received data; then, (II) compare the entropy with the maximum value; and, finally, (III) make decision: H{sub 1} is assumed if the difference is large compared to pre-assigned threshold and H{sub 0} is otherwise assumed. The test statistics will be different between entropies under H{sub 0} and H{sub 1}. Here, we shall show the simulated results for detecting stationary and non-stationary signals in noise, and results on detection of defects in a Plexiglas bar using an ultrasonic experiment conducted by Hughes. {copyright} {ital 1996 American Institute of Physics.}

  10. First direct measurements of behavioural responses by Cuvier's beaked whales to mid-frequency active sonar.

    PubMed

    DeRuiter, Stacy L; Southall, Brandon L; Calambokidis, John; Zimmer, Walter M X; Sadykova, Dinara; Falcone, Erin A; Friedlaender, Ari S; Joseph, John E; Moretti, David; Schorr, Gregory S; Thomas, Len; Tyack, Peter L

    2013-08-23

    Most marine mammal- strandings coincident with naval sonar exercises have involved Cuvier's beaked whales (Ziphius cavirostris). We recorded animal movement and acoustic data on two tagged Ziphius and obtained the first direct measurements of behavioural responses of this species to mid-frequency active (MFA) sonar signals. Each recording included a 30-min playback (one 1.6-s simulated MFA sonar signal repeated every 25 s); one whale was also incidentally exposed to MFA sonar from distant naval exercises. Whales responded strongly to playbacks at low received levels (RLs; 89-127 dB re 1 µPa): after ceasing normal fluking and echolocation, they swam rapidly, silently away, extending both dive duration and subsequent non-foraging interval. Distant sonar exercises (78-106 dB re 1 µPa) did not elicit such responses, suggesting that context may moderate reactions. The observed responses to playback occurred at RLs well below current regulatory thresholds; equivalent responses to operational sonars could elevate stranding risk and reduce foraging efficiency.

  11. Marine Mammal Active Sonar Test 2004 (MAST 2004)

    NASA Astrophysics Data System (ADS)

    Stein, Peter J.; Vandiver, Amy; Edelson, Geoffrey S.; Frankel, Adam S.; Clark, Christopher W.

    2004-05-01

    The Marine Mammal Active Sonar Test was conducted in January 2004 off the central California coast during the gray whale migration. The purpose of the test was to collect data to significantly advance active sonar detection, classification, and tracking of marine mammals out to ranges of 1 mile. The R/V NEW HORIZON was moored in the migration path. Two different sonar systems operating between 210 and 220 dB were deployed off the vessel, the IMAPS phased array sonar system that operates from 20-30 kHz and the MAST mechanical system that uses rotating parabolic transducers operating from 30 to 40 kHz. Marine mammal observers were deployed on the bluffs overlooking the experiment and aboard the NEW HORIZON. The observers tracked the whales using electronic theodelites, providing ground truth for the sonar systems. They also looked for any severe reactions from the animals, and called for a shutdown if any marine mammals were observed within 100 m of the sonar. Here, we discuss the experiment and the results to date, including any reaction of the whales to the sonar system. We will also touch on the legal battle to conduct the experiment, and lessons learned.

  12. Delphinid behavioral responses to incidental mid-frequency active sonar.

    PubMed

    Henderson, E Elizabeth; Smith, Michael H; Gassmann, Martin; Wiggins, Sean M; Douglas, Annie B; Hildebrand, John A

    2014-10-01

    Opportunistic observations of behavioral responses by delphinids to incidental mid-frequency active (MFA) sonar were recorded in the Southern California Bight from 2004 through 2008 using visual focal follows, static hydrophones, and autonomous recorders. Sound pressure levels were calculated between 2 and 8 kHz. Surface behavioral responses were observed in 26 groups from at least three species of 46 groups out of five species encountered during MFA sonar incidents. Responses included changes in behavioral state or direction of travel, changes in vocalization rates and call intensity, or a lack of vocalizations while MFA sonar occurred. However, 46% of focal groups not exposed to sonar also changed their behavior, and 43% of focal groups exposed to sonar did not change their behavior. Mean peak sound pressure levels when a behavioral response occurred were around 122 dB re: 1 μPa. Acoustic localizations of dolphin groups exhibiting a response gave insight into nighttime movement patterns and provided evidence that impacts of sonar may be mediated by behavioral state. The lack of response in some cases may indicate a tolerance of or habituation to MFA sonar by local populations; however, the responses that occur at lower received levels may point to some sensitization as well.

  13. Examining the robustness of automated aural classification of active sonar echoes.

    PubMed

    Murphy, Stefan M; Hines, Paul C

    2014-02-01

    Active sonar systems are used to detect underwater man-made objects of interest (targets) that are too quiet to be reliably detected with passive sonar. Performance of active sonar can be degraded by false alarms caused by echoes returned from geological seabed structures (clutter) in shallow regions. To reduce false alarms, a method of distinguishing target echoes from clutter echoes is required. Research has demonstrated that perceptual-based signal features similar to those employed in the human auditory system can be used to automatically discriminate between target and clutter echoes, thereby reducing the number of false alarms and improving sonar performance. An active sonar experiment on the Malta Plateau in the Mediterranean Sea was conducted during the Clutter07 sea trial and repeated during the Clutter09 sea trial. The dataset consists of more than 95,000 pulse-compressed echoes returned from two targets and many geological clutter objects. These echoes were processed using an automatic classifier that quantifies the timbre of each echo using a number of perceptual signal features. Using echoes from 2007, the aural classifier was trained to establish a boundary between targets and clutter in the feature space. Temporal robustness was then investigated by testing the classifier on echoes from the 2009 experiment.

  14. Method and Apparatus for Improved Active Sonar Using Singular Value Decomposition Filtering

    DTIC Science & Technology

    2007-06-26

    of both projector and receiver of the sonar, type of sonar, range resolution of the sonar, number of eigenrays striking the surface and bottom of the...sonar environment, number of eigenrays striking the target, ray trajectories to the target, and surface and bottom scattering strength as a function...the propagation channel or any other non- homogeneous responses due to channel and/or target interactions. [0052] The system for improved active sonar

  15. Graphical derivations of radar, sonar, and communication signals

    NASA Technical Reports Server (NTRS)

    Altes, R. A.; Titlebaum, E. L.

    1975-01-01

    The designer of a communication system often has knowledge concerning the changes in distance between transmitter and receiver as a function of time. This information can be exploited to reduce multipath interference via proper signal design. A radar or sonar may also have good a priori information about possible target trajectories. Such knowledge can again be used to reduce the receiver's response to clutter (MTI), to enhance signal-to-noise ratio, or to simplify receiver design. There are also situations in which prior knowledge about trajectories is lacking. The system should then utilize a single-filter pair which is insensitive to the effects induced by relative motion between transmitter, receiver, and reflectors. For waveforms with large time-bandwidth products, such as long pulse trains, it is possible to graphically derive signal formats for both situations (trajectory known and unknown). Although the exact form of the signal is sometimes not specified by the graphical procedure, the problem in such cases is reduced to one which has already been solved, i.e., the generation of an impulse equivalent code.

  16. Active sonar, beaked whales and European regional policy.

    PubMed

    Dolman, Sarah J; Evans, Peter G H; Notarbartolo-di-Sciara, Giuseppe; Frisch, Heidrun

    2011-01-01

    Various reviews, resolutions and guidance from international and regional fora have been produced in recent years that acknowledge the significance of marine noise and its potential impacts on cetaceans. Within Europe, ACCOBAMS and ASCOBANS have shown increasing attention to the issue. The literature highlights concerns surrounding the negative impacts of active sonar on beaked whales in particular, where concerns primarily relate to the use of mid-frequency active sonar (1-10kHz), as used particularly in military exercises. The authors review the efforts that European regional policies have undertaken to acknowledge and manage possible negative impacts of active sonar and how these might assist the transition from scientific research to policy implementation, including effective management and mitigation measures at a national level.

  17. Sonar signal processing using probabilistic signal and ocean environmental models.

    PubMed

    Culver, R Lee; Camin, H John

    2008-12-01

    Acoustic signals propagating through the ocean are refracted, scattered, and attenuated by the ocean volume and boundaries. Many aspects of how the ocean affects acoustic propagation are understood, such that the characteristics of a received signal can often be predicted with some degree of certainty. However, acoustic ocean parameters vary with time and location in a manner that is not, and cannot be, precisely known; some uncertainty will always remain. For this reason, the characteristics of the received signal can never be precisely predicted and must be described in probabilistic terms. A signal processing structure recently developed relies on knowledge of the ocean environment to predict the statistical characteristics of the received signal, and incorporates this description into the processor in order to detect and classify targets. Acoustic measurements at 250 Hz from the 1996 Strait of Gibraltar Acoustic Monitoring Experiment are used to illustrate how the processor utilizes environmental data to classify source depth and to underscore the importance of environmental model fidelity and completeness.

  18. 3S2: Behavioral Response Studies of Cetaceans to Naval Sonar Signals in Norwegian Waters

    DTIC Science & Technology

    2011-09-30

    species of whales : bottlenose whales , minke whales , and humpback whales to Low Frequency Active Sonar (LFAS) and Mid Frequency Active Sonar (MFAS...our goal is to conduct experiments to test the effectiveness of ramp-up in humpback whales . OBJECTIVES In this research project, our...study of the effectiveness of ramp-up as a mitigation method with abundant and relatively easy-to-study humpback whales , Megaptera novaeangliae; 3

  19. Behavioral Response of Dolphins to Signals Simulating Mid-Frequency Sonar

    DTIC Science & Technology

    2011-09-30

    similar to tactical sonar signals; (2) apply a scoring analysis to qualitative descriptors of the observed responses; (3) calculate a behavioral dose ... response function (DRF) for delphinid and otariid species exposed to mid-frequency signals; (4) record heart rate on a subset of the dolphins and sea

  20. "Gas and fat embolic syndrome" involving a mass stranding of beaked whales (family Ziphiidae) exposed to anthropogenic sonar signals.

    PubMed

    Fernández, A; Edwards, J F; Rodríguez, F; Espinosa de los Monteros, A; Herráez, P; Castro, P; Jaber, J R; Martín, V; Arbelo, M

    2005-07-01

    A study of the lesions of beaked whales (BWs) in a recent mass stranding in the Canary Islands following naval exercises provides a possible explanation of the relationship between anthropogenic, acoustic (sonar) activities and the stranding and death of marine mammals. Fourteen BWs were stranded in the Canary Islands close to the site of an international naval exercise (Neo-Tapon 2002) held on 24 September 2002. Strandings began about 4 hours after the onset of midfrequency sonar activity. Eight Cuvier's BWs (Ziphius cavirostris), one Blainville's BW (Mesoplodon densirostris), and one Gervais' BW (Mesoplodon europaeus) were examined postmortem and studied histopathologically. No inflammatory or neoplastic processes were noted, and no pathogens were identified. Macroscopically, whales had severe, diffuse congestion and hemorrhage, especially around the acoustic jaw fat, ears, brain, and kidneys. Gas bubble-associated lesions and fat embolism were observed in the vessels and parenchyma of vital organs. In vivo bubble formation associated with sonar exposure that may have been exacerbated by modified diving behavior caused nitrogen supersaturation above a threshold value normally tolerated by the tissues (as occurs in decompression sickness). Alternatively, the effect that sonar has on tissues that have been supersaturated with nitrogen gas could be such that it lowers the threshold for the expansion of in vivo bubble precursors (gas nuclei). Exclusively or in combination, these mechanisms may enhance and maintain bubble growth or initiate embolism. Severely injured whales died or became stranded and died due to cardiovascular collapse during beaching. The present study demonstrates a new pathologic entity in cetaceans. The syndrome is apparently induced by exposure to mid-frequency sonar signals and particularly affects deep, long-duration, repetitive-diving species like BWs.

  1. Signal-to-symbol transformation: a summary of HASP/SIAP case study (sonar data)

    SciTech Connect

    Penny Nii, H.

    1983-01-01

    In the past fifteen years, ai scientists have built several signal interpretation, or understanding, programs. HASP/SIAP is one such program which tries to interest the meaning of sonar data in a particular context. An attempt is made to present a methodology for understanding signal data and to show that the traditional signal processing is but one part of the interpretation task. HASP/SIAP is also an expert system. 12 references.

  2. 75 FR 5055 - Taking and Importing Marine Mammals; U.S. Navy's Atlantic Fleet Active Sonar Training (AFAST)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-01

    .... Navy's Atlantic Fleet Active Sonar Training (AFAST) AGENCY: National Marine Fisheries Service (NMFS..., testing, and evaluation (RDT&E) activities to be conducted within the Atlantic Fleet Active Sonar Training... side mine hunting sonar in the AFAST Study area, which reduces use from 4474 hours annually to 0....

  3. The application of m-sequences to bi-static active sonar

    NASA Astrophysics Data System (ADS)

    Deferrari, Harry A.

    2003-10-01

    The m-sequences are ideal pulse compression signals that combine the energy of CW with the resolution of a pulse. Successful applications include numerous acoustic propagation experiments and the Global Positioning System. Yet, early attempts (circa 1960) to apply m-sequences to mono-static active sonar were unsuccessful. Through the years, Birdsall, Metzger and others have developed a body of theory, numerical methods and at-sea demonstrations that establish the feasibility of a novel bi-static approach-one that holds promise in high reverberation shallow water environs. An analysis is presented here. The approach includes (1) continuous transmission of long m-sequences (2) synchronous sampling to form a CON (Complete Ortho-Normal) data set; (3) direct blast removal by HCCO (Hyperspace Cancellation by Coordinate Zeroing); and (4) a full range waveform Doppler search. Ultra-fast Hadamard Transforms speed up the direct waveform pulse m-sequence pulse compression and the inverse pulse waveform transform and thereby allow timely execution of the intensive computational burden. The result is a demonstrable approach that produces a gain of 30 dB over a simple pulse and 10 dB over other sonar signals. In the end, the approach requires continuous transmission and reception as opposed to ping and listen an awkward concept at first.

  4. Radar/sonar signal design for bounded Doppler shifts

    NASA Astrophysics Data System (ADS)

    Altes, R. A.

    1982-07-01

    In many detection and estimation problems, Doppler frequency shifts are bounded. For clutter or multipath that is uniformly distributed in range and symmetrically distributed in Doppler shift relative to the signal, detectability of a point target or a communication signal is improved by minimizing the weighted volume of the magnitude-squared autoambiguity function. When clutter Doppler shifts are bounded, this volume is in a strip containing the range axis on the range-Doppler plane. For scattering function estimation, e.g., for weather radar, Doppler flow meters, and distributed target classifiers, it is again relevant to minimize ambiguity volume in a strip. Strip volume is minimized by using a pulse train, but such a signal has unacceptably large range sidelobe for most applications. Other waveforms that have relatively small sidelobe level within a strip on the range-Doppler plane, as well as small ambiguity volume in the strip, are obtained. The waveforms are composed of pulse pairs that are phase modulated with Golay complementary codes.

  5. Risk Functions of Dolphins and Sea Lions Exposed to Sonar Signals.

    PubMed

    Houser, Dorian S; Martin, Steven W; Finneran, James J

    2016-01-01

    Acoustic dose-response functions have been recommended as a means of predicting behavioral impacts on marine mammals from anthropogenic noise exposure. Thirty bottlenose dolphins and fifteen sea lions participated in a controlled exposure study to explore dose-response relationships to the received level of a simulated sonar signal. Both species showed an increase in the probability of response and in the severity of response with increased received levels. Differences in species sensitivity were noted in habituation and the impact of age on responsiveness.

  6. Multimodal integration of micro-Doppler sonar and auditory signals for behavior classification with convolutional networks.

    PubMed

    Dura-Bernal, Salvador; Garreau, Guillaume; Georgiou, Julius; Andreou, Andreas G; Denham, Susan L; Wennekers, Thomas

    2013-10-01

    The ability to recognize the behavior of individuals is of great interest in the general field of safety (e.g. building security, crowd control, transport analysis, independent living for the elderly). Here we report a new real-time acoustic system for human action and behavior recognition that integrates passive audio and active micro-Doppler sonar signatures over multiple time scales. The system architecture is based on a six-layer convolutional neural network, trained and evaluated using a dataset of 10 subjects performing seven different behaviors. Probabilistic combination of system output through time for each modality separately yields 94% (passive audio) and 91% (micro-Doppler sonar) correct behavior classification; probabilistic multimodal integration increases classification performance to 98%. This study supports the efficacy of micro-Doppler sonar systems in characterizing human actions, which can then be efficiently classified using ConvNets. It also demonstrates that the integration of multiple sources of acoustic information can significantly improve the system's performance.

  7. Application of musical timbre discrimination features to active sonar classification

    NASA Astrophysics Data System (ADS)

    Young, Victor W.; Hines, Paul C.; Pecknold, Sean

    2005-04-01

    In musical acoustics significant effort has been devoted to uncovering the physical basis of timbre perception. Most investigations into timbre rely on multidimensional scaling (MDS), in which different musical sounds are arranged as points in multidimensional space. The Euclidean distance between points corresponds to the perceptual distance between sounds and the multidimensional axes are linked to measurable properties of the sounds. MDS has identified numerous temporal and spectral features believed to be important to timbre perception. There is reason to believe that some of these features may have wider application in the disparate field of underwater acoustics, since anecdotal evidence suggests active sonar returns from metallic objects sound different than natural clutter returns when auralized by human operators. This is particularly encouraging since attempts to develop robust automatic classifiers capable of target-clutter discrimination over a wide range of operational conditions have met with limited success. Spectral features relevant to target-clutter discrimination are believed to include click-pitch and envelope irregularity; relevant temporal features are believed to include duration, sub-band attack/decay time, and time separation pitch. Preliminary results from an investigation into the role of these timbre features in target-clutter discrimination will be presented. [Work supported by NSERC and GDC.

  8. Active Fish Tracking Sonar (AFTS) for Assessing Fish Behavior

    SciTech Connect

    Hedgepeth, J; Johnson, Gary E. ); Skalski, John R.; Burczynski, J

    2002-11-01

    Active fish tracking sonars (AFTS) were used in 2001 to study fish movement in response to intake occlusion plates at The Dalles Dam on the Columbia River. AFTS provides three-dimensional fish tracks by aligning the axis of a split-beam transducer with a fish target. High-speed stepper motors move the transducer so that a tracked target remains on-axis. Occlusion plates with lateral extensions covered the top half of the turbine intakes to produce a fish friendly near-dam environment. Two AFTS were positioned at the center of Main Unit 1, one each for monitoring installed and removed plate conditions. A regression analysis showed that occlusion plates had pronounced effects on fish movement along the dam. The plates appeared to inhibit movement toward the spillway, movement toward the dam (especially in front of the turbine intake), and movement downward toward the turbines. Fish fate (as opposed to movement directions from regression slopes) into particular areas was determined using Markov-chain analysis. The sluiceway (a safer passage route above the turbine intake) zone of influence was larger with the occlusion plates installed, contrary to the regression results. In addition, the probability of passage out the near turbine and bottom sides of the sample volume was about 50% lower with occlusion plates installed.

  9. Modeling interface roughness scattering in a layered seabed for normal-incident chirp sonar signals.

    PubMed

    Tang, Dajun; Hefner, Brian T

    2012-04-01

    Downward looking sonar, such as the chirp sonar, is widely used as a sediment survey tool in shallow water environments. Inversion of geo-acoustic parameters from such sonar data precedes the availability of forward models. An exact numerical model is developed to initiate the simulation of the acoustic field produced by such a sonar in the presence of multiple rough interfaces. The sediment layers are assumed to be fluid layers with non-intercepting rough interfaces.

  10. Analysis of signals under compositional noise with applications to SONAR data

    SciTech Connect

    Tucker, J. Derek; Wu, Wei; Srivastava, Anuj

    2013-07-09

    In this paper, we consider the problem of denoising and classification of SONAR signals observed under compositional noise, i.e., they have been warped randomly along the x-axis. The traditional techniques do not account for such noise and, consequently, cannot provide a robust classification of signals. We apply a recent framework that: 1) uses a distance-based objective function for data alignment and noise reduction; and 2) leads to warping-invariant distances between signals for robust clustering and classification. We use this framework to introduce two distances that can be used for signal classification: a) a y-distance, which is the distance between the aligned signals; and b) an x-distance that measures the amount of warping needed to align the signals. We focus on the task of clustering and classifying objects, using acoustic spectrum (acoustic color), which is complicated by the uncertainties in aspect angles at data collections. Small changes in the aspect angles corrupt signals in a way that amounts to compositional noise. As a result, we demonstrate the use of the developed metrics in classification of acoustic color data and highlight improvements in signal classification over current methods.

  11. Analysis of signals under compositional noise with applications to SONAR data

    DOE PAGES

    Tucker, J. Derek; Wu, Wei; Srivastava, Anuj

    2013-07-09

    In this paper, we consider the problem of denoising and classification of SONAR signals observed under compositional noise, i.e., they have been warped randomly along the x-axis. The traditional techniques do not account for such noise and, consequently, cannot provide a robust classification of signals. We apply a recent framework that: 1) uses a distance-based objective function for data alignment and noise reduction; and 2) leads to warping-invariant distances between signals for robust clustering and classification. We use this framework to introduce two distances that can be used for signal classification: a) a y-distance, which is the distance between themore » aligned signals; and b) an x-distance that measures the amount of warping needed to align the signals. We focus on the task of clustering and classifying objects, using acoustic spectrum (acoustic color), which is complicated by the uncertainties in aspect angles at data collections. Small changes in the aspect angles corrupt signals in a way that amounts to compositional noise. As a result, we demonstrate the use of the developed metrics in classification of acoustic color data and highlight improvements in signal classification over current methods.« less

  12. Behavioral responses of California sea lions to mid-frequency (3250-3450 Hz) sonar signals.

    PubMed

    Houser, Dorian S; Martin, Stephen W; Finneran, James J

    2013-12-01

    Military sonar has the potential to negatively impact marine mammals. To investigate factors affecting behavioral disruption in California sea lions (Zalophus californianus), fifteen sea lions participated in a controlled exposure study using a simulated tactical sonar signal (1 s duration, 3250-3450 Hz) as a stimulus. Subjects were placed into groups of three and each group received a stimulus exposure of 125, 140, 155, 170, or 185 dB re: 1 μPa (rms). Each subject was trained to swim across an enclosure, touch a paddle, and return to the start location. Sound exposures occurred at the mid-point of the enclosure. Control and exposure sessions were run consecutively and each consisted of ten, 30-s trials. The occurrence and severity of behavioral responses were used to create acoustic dose-response and dose-severity functions. Age of the subject significantly affected the dose-response relationship, but not the dose-severity relationship. Repetitive exposures did not affect the dose-response relationship.

  13. Assessing Beaked Whale Reproduction and Stress Response Relative to Sonar Activity at the Atlantic Undersea Test and Evaluation Center

    DTIC Science & Technology

    2014-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Assessing Beaked Whale Reproduction and Stress Response...both groups of animals to investigate whether there is a relationship between sonar activity, stress measures, and reproductive rates, to assess... Reproduction and Stress Response Relative to Sonar Activity at the Atlantic Undersea Test and Evaluation Center (AUTEC) 5a. CONTRACT NUMBER 5b. GRANT

  14. Behavioral responses by grey seals (Halichoerus grypus) to high frequency sonar.

    PubMed

    Hastie, Gordon D; Donovan, Carl; Götz, Thomas; Janik, Vincent M

    2014-02-15

    The use of high frequency sonar is now commonplace in the marine environment. Most marine mammals rely on sound to navigate, and for detecting prey, and there is the potential that the acoustic signals of sonar could cause behavioral responses. To investigate this, we carried out behavioral response tests with grey seals to two sonar systems (200 and 375 kHz systems). Results showed that both systems had significant effects on the seals behavior; when the 200 kHz sonar was active, seals spent significantly more time hauled out and, although seals remained swimming during operation of the 375 kHz sonar, they were distributed further from the sonar. The results show that although peak sonar frequencies may be above marine mammal hearing ranges, high levels of sound can be produced within their hearing ranges that elicit behavioral responses; this has clear implications for the widespread use of sonar in the marine environment.

  15. Antifade sonar employs acoustic field diversity to recover signals from multipath fading

    SciTech Connect

    Lubman, D.

    1996-04-01

    Co-located pressure and particle motion (PM) hydrophones together with four-channel diversity combiners may be used to recover signals from multipath fading. Multipath fading is important in both shallow and deep water propagation and can be an important source of signal loss. The acoustic field diversity concept arises from the notion of conservation of signal energy and the observation that in rooms at least, the total acoustic energy density is the sum of potential energy (scalar field-sound pressure) and kinetic energy (vector field-sound PM) portions. One pressure hydrophone determines acoustic potential energy density at a point. In principle, three PM sensors (displacement, velocity, or acceleration) directed along orthogonal axes describe the kinetic energy density at a point. For a single plane wave, the time-averaged potential and kinetic field energies are identical everywhere. In multipath interference, however, potential and kinetic field energies at a point are partitioned unequally, depending mainly on relative signal phases. Thus, when pressure signals are in deep fade, abundant kinetic field signal energy may be available at that location. Performance benefits require a degree of uncorrelated fading between channels. The expectation of nearly uncorrelated fading is motivated from room theory. Performance benefits for sonar limited by independent Rayleigh fading are suggested by analogy to antifade radio. Average SNR can be improved by several decibels, holding time on target is multiplied manifold, and the bit error rate for data communication is reduced substantially. {copyright} {ital 1996 American Institute of Physics.}

  16. 77 FR 52317 - Record of Decision for Surveillance Towed Array Sensor System Low Frequency Active Sonar

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-29

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Department of the Navy Record of Decision for Surveillance Towed Array Sensor System Low Frequency Active... Array Sensor System Low Frequency Active (SURTASS LFA) sonar systems with certain...

  17. Signal classification using global dynamical models, Part II: SONAR data analysis

    SciTech Connect

    Kremliovsky, M.; Kadtke, J.

    1996-06-01

    In Part I of this paper, we described a numerical method for nonlinear signal detection and classification which made use of techniques borrowed from dynamical systems theory. Here in Part II of the paper, we will describe an example of data analysis using this method, for data consisting of open ocean acoustic (SONAR) recordings of marine mammal transients, supplied from NUWC sources. The purpose here is two-fold: first to give a more operational description of the technique and provide rules-of-thumb for parameter choices; and second to discuss some new issues raised by the analysis of non-ideal (real-world) data sets. The particular data set considered here is quite non-stationary, relatively noisy, is not clearly localized in the background, and as such provides a difficult challenge for most detection/classification schemes. {copyright} {ital 1996 American Institute of Physics.}

  18. Signal classification using global dynamical models, Part II: SONAR data analysis

    NASA Astrophysics Data System (ADS)

    Kremliovsky, Michael; Kadtke, James

    1996-06-01

    In Part I of this paper, we described a numerical method for nonlinear signal detection and classification which made use of techniques borrowed from dynamical systems theory. Here in Part II of the paper, we will describe an example of data analysis using this method, for data consisting of open ocean acoustic (SONAR) recordings of marine mammal transients, supplied from NUWC sources. The purpose here is two-fold: first to give a more operational description of the technique and provide rules-of-thumb for parameter choices; and second to discuss some new issues raised by the analysis of non-ideal (real-world) data sets. The particular data set considered here is quite non-stationary, relatively noisy, is not clearly localized in the background, and as such provides a difficult challenge for most detection/classification schemes.

  19. Continuous Active Sonar for Undersea Vehicles Final Report: Input of Factor Graphs into the Detection, Classification, and Localization Chain and Continuous Active SONAR in Undersea Vehicles

    DTIC Science & Technology

    2015-12-31

    simply adding the two branches. Equation 50 gives the final step before substituting the previously found covanances. (50) where G ~ (v3 + crvz( c [) H ... H can be compared to c since they both are matrices relating the measurement to the state. The variable R in the Kalman filter is the covariance...Wakayama, C . (2013). Multistatic Tracking for Continuous Active Sonar using Doppler-Bearing Measurements. 16th International Conference on Information

  20. Sidescan sonar imagery of widespread fossil and active cold seeps along the central Chilean continental margin

    NASA Astrophysics Data System (ADS)

    Klaucke, Ingo; Weinrebe, Wilhelm; Linke, Peter; Kläschen, Dirk; Bialas, Jörg

    2012-12-01

    The central Chilean subduction zone between 35°S and 37°S was investigated in order to identify, document and possibly understand fluid flow and fluid venting within the forearc region. Several areas were mapped using multibeam bathymetry and backscatter, high-resolution sidescan sonar, chirp subbottom profiling and reflection seismic data. On a subsequent cruise ground-truthing observations were made using a video sled. In general, this dataset shows surprisingly little evidence of fluid venting along the mid-slope region, in contrast to other subduction zones such as Central America and New Zealand. There were abundant indications of active and predominantly fossil fluid venting along the upper slope between 36.5°S and 36.8°S at the seaward margin of an intraslope basin. Here, backscatter anomalies suggest widespread authigenic carbonate deposits, likely the result of methane-rich fluid expulsion. There is unpublished evidence that these fluids are of biogenic origin and generated within the slope sediments, similar to other accretionary margins but in contrast to the erosional margin off Central America, where fluids have geochemical signals indicating an origin from the subducting plate.

  1. Patterns of Occurrence and Marine Mammal Acoustic Behavior in Relation to Navy Sonar Activity Off Jacksonville, Florida.

    PubMed

    Oswald, Julie N; Norris, Thomas F; Yack, Tina M; Ferguson, Elizabeth L; Kumar, Anurag; Nissen, Jene; Bell, Joel

    2016-01-01

    Passive acoustic data collected from marine autonomous recording units deployed off Jacksonville, FL (from 13 September to 8 October 2009 and 3 December 2009 to 8 January 2010), were analyzed for detection of cetaceans and Navy sonar. Cetaceans detected included Balaenoptera acutorostrata, Eubalaena glacialis, B. borealis, Physeter macrocephalus, blackfish, and delphinids. E. glacialis were detected at shallow and, somewhat unexpectedly, deep sites. P. macrocephalus were characterized by a strong diel pattern. B. acutorostrata showed the strongest relationship between sonar activity and vocal behavior. These results provide a preliminary assessment of cetacean occurrence off Jacksonville and new insights on vocal responses to sonar.

  2. A Risk Function for Behavioral Disruption of Blainville’s Beaked Whales (Mesoplodon densirostris) from Mid-Frequency Active Sonar

    PubMed Central

    Moretti, David; Thomas, Len; Marques, Tiago; Harwood, John; Dilley, Ashley; Neales, Bert; Shaffer, Jessica; McCarthy, Elena; New, Leslie; Jarvis, Susan; Morrissey, Ronald

    2014-01-01

    There is increasing concern about the potential effects of noise pollution on marine life in the world’s oceans. For marine mammals, anthropogenic sounds may cause behavioral disruption, and this can be quantified using a risk function that relates sound exposure to a measured behavioral response. Beaked whales are a taxon of deep diving whales that may be particularly susceptible to naval sonar as the species has been associated with sonar-related mass stranding events. Here we derive the first empirical risk function for Blainville’s beaked whales (Mesoplodon densirostris) by combining in situ data from passive acoustic monitoring of animal vocalizations and navy sonar operations with precise ship tracks and sound field modeling. The hydrophone array at the Atlantic Undersea Test and Evaluation Center, Bahamas, was used to locate vocalizing groups of Blainville’s beaked whales and identify sonar transmissions before, during, and after Mid-Frequency Active (MFA) sonar operations. Sonar transmission times and source levels were combined with ship tracks using a sound propagation model to estimate the received level (RL) at each hydrophone. A generalized additive model was fitted to data to model the presence or absence of the start of foraging dives in 30-minute periods as a function of the corresponding sonar RL at the hydrophone closest to the center of each group. This model was then used to construct a risk function that can be used to estimate the probability of a behavioral change (cessation of foraging) the individual members of a Blainville’s beaked whale population might experience as a function of sonar RL. The function predicts a 0.5 probability of disturbance at a RL of 150dBrms re µPa (CI: 144 to 155) This is 15dB lower than the level used historically by the US Navy in their risk assessments but 10 dB higher than the current 140 dB step-function. PMID:24465477

  3. A risk function for behavioral disruption of Blainville's beaked whales (Mesoplodon densirostris) from mid-frequency active sonar.

    PubMed

    Moretti, David; Thomas, Len; Marques, Tiago; Harwood, John; Dilley, Ashley; Neales, Bert; Shaffer, Jessica; McCarthy, Elena; New, Leslie; Jarvis, Susan; Morrissey, Ronald

    2014-01-01

    There is increasing concern about the potential effects of noise pollution on marine life in the world's oceans. For marine mammals, anthropogenic sounds may cause behavioral disruption, and this can be quantified using a risk function that relates sound exposure to a measured behavioral response. Beaked whales are a taxon of deep diving whales that may be particularly susceptible to naval sonar as the species has been associated with sonar-related mass stranding events. Here we derive the first empirical risk function for Blainville's beaked whales (Mesoplodon densirostris) by combining in situ data from passive acoustic monitoring of animal vocalizations and navy sonar operations with precise ship tracks and sound field modeling. The hydrophone array at the Atlantic Undersea Test and Evaluation Center, Bahamas, was used to locate vocalizing groups of Blainville's beaked whales and identify sonar transmissions before, during, and after Mid-Frequency Active (MFA) sonar operations. Sonar transmission times and source levels were combined with ship tracks using a sound propagation model to estimate the received level (RL) at each hydrophone. A generalized additive model was fitted to data to model the presence or absence of the start of foraging dives in 30-minute periods as a function of the corresponding sonar RL at the hydrophone closest to the center of each group. This model was then used to construct a risk function that can be used to estimate the probability of a behavioral change (cessation of foraging) the individual members of a Blainville's beaked whale population might experience as a function of sonar RL. The function predicts a 0.5 probability of disturbance at a RL of 150 dBrms re µPa (CI: 144 to 155) This is 15dB lower than the level used historically by the US Navy in their risk assessments but 10 dB higher than the current 140 dB step-function.

  4. 3S2: Behavioral Response Studies of Cetaceans to Navy Sonar Signals in Norwegian Waters

    DTIC Science & Technology

    2015-09-30

    the 1-2 kHz sonar exposure with a tagged minke whale. Data in the top 4 panels were derived from observations from the trackboat (‘ MOB ’). ‘Direction... MOB ’ refers to the direction of animal movement, while ‘Directness MOB ’ refers to the directness of the track from 0 (circular movement) to 1.0

  5. Gain control in the sonar of odontocetes.

    PubMed

    Ya Supin, Alexander; Nachtigall, Paul E

    2013-06-01

    The sonar of odontocetes processes echo-signals within a wide range of echo levels. The level of echoes varies widely by tens of decibels depending on the level of the emitted sonar pulse, the target strength, the distance to the target, and the sound absorption by the water media. The auditory system of odontocetes must be capable of effective perception, analysis, and discrimination of echo-signals within all this variability. The sonar of odontocetes has several mechanisms to compensate for the echo-level variation (gain control). To date, several mechanisms of the biosonar gain control have been revealed in odontocetes: (1) adjustment of emitted sonar pulse levels (the longer the distance to the target, the higher the level of the emitted pulse), (2) short-term variation of hearing sensitivity based on forward masking of the echo by the preceding self-heard emitted pulse and subsequent release from the masking, and (3) active long-term control of hearing sensitivity. Recent investigations with the use of the auditory evoked-potential technique have demonstrated that these mechanisms effectively minimize the variation of the response to the echo when either the emitted sonar pulse level, or the target distance, or both vary within a wide range. A short review of these data is presented herein.

  6. 3S2 - Behavioral Response Studies of Cetaceans to Naval Sonar Signals in Norwegian Waters

    DTIC Science & Technology

    2012-09-30

    behavioural response thresholds during experimental exposures, and to compare these to responses to no-sonar controls and playback of killer whale ...research effort (see related programs) with killer , sperm, and long-finned pilot whales provides a dataset that enables comparative analysis of...successful collection of additional playback of killer whale sounds to long- finned pilot whales and sperm whales in the 2010 baseline cruise under this

  7. 3S2 - Behavioral Response Studies of Cetaceans to Navy Sonar Signals in Norwegian Waters

    DTIC Science & Technology

    2012-09-30

    behavioral response thresholds during experimental exposures, and to compare these to responses to no-sonar controls and playback of killer whale ...research effort (see related programs) with killer , sperm, and long-finned pilot whales provides a dataset that enables comparative analysis of behavioral...experiments of killer whale sounds to long-finned pilot whales and sperm whales in the 2010 baseline cruise under this award, the behavioral responses of

  8. 3S2: Behavioral Response Studies of Cetaceans to Navy Sonar Signals in Norwegian Waters

    DTIC Science & Technology

    2013-09-30

    experiments, and to compare these to responses to no-sonar controls and playback of killer whale sounds; 2.) Conduct a directed study on the...experiments follow the same protocol of escalating the level received by the whale subject in order to identify response thresholds. Playback of killer ...focused upon conducting playback experiments of mammal-eating killer whale sounds to long-finned pilot whales with additional control stumuli also

  9. Behavioral responses of herring (Clupea harengus) to 1-2 and 6-7 kHz sonar signals and killer whale feeding sounds.

    PubMed

    Doksaeter, Lise; Rune Godo, Olav; Olav Handegard, Nils; Kvadsheim, Petter H; Lam, Frans-Peter A; Donovan, Carl; Miller, Patrick J O

    2009-01-01

    Military antisubmarine sonars produce intense sounds within the hearing range of most clupeid fish. The behavioral reactions of overwintering herring (Clupea harengus) to sonar signals of two different frequency ranges (1-2 and 6-7 kHz), and to playback of killer whale feeding sounds, were tested in controlled exposure experiments in Vestfjorden, Norway, November 2006. The behavior of free ranging herring was monitored by two upward-looking echosounders. A vessel towing an operational naval sonar source approached and passed over one of them in a block design setup. No significant escape reactions, either vertically or horizontally, were detected in response to sonar transmissions. Killer whale feeding sounds induced vertical and horizontal movements of herring. The results indicate that neither transmission of 1-2 kHz nor 6-7 kHz have significant negative influence on herring on the received sound pressure level tested (127-197 and 139-209 dB(rms) re 1 microPa, respectively). Military sonars of such frequencies and source levels may thus be operated in areas of overwintering herring without substantially affecting herring behavior or herring fishery. The avoidance during playback of killer whale sounds demonstrates the nature of an avoidance reaction and the ability of the experimental design to reveal it.

  10. 75 FR 81284 - Nationwide Use of High Frequency and Ultra High Frequency Active SONAR Technology; Draft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-27

    ... SONAR technologies that operate at frequencies of 50 kiloHertz (kHz) and greater from mobile platforms... proposes to use HF and UHF SONAR technology from mobile platforms nationwide. Mobile platforms include...-specific, non-mobile operating scenarios or newly developed technologies fall outside of the scope of...

  11. Miniature sonar fish tag

    NASA Technical Reports Server (NTRS)

    Lovelady, R. W.; Ferguson, R. L.

    1975-01-01

    Self-powered sonar device may be implanted in body of fish. It transmits signal that can be detected with portable tracking gear or by automatic detection-and-tracking system. Operating life of over 4000 hours may be expected. Device itself may be used almost indefinitely.

  12. Potential Population Consequences of Active Sonar Disturbance in Atlantic Herring: Estimating the Maximum Risk.

    PubMed

    Sivle, Lise Doksæter; Kvadsheim, Petter Helgevold; Ainslie, Michael

    2016-01-01

    Effects of noise on fish populations may be predicted by the population consequence of acoustic disturbance (PCAD) model. We have predicted the potential risk of population disturbance when the highest sound exposure level (SEL) at which adult herring do not respond to naval sonar (SEL(0)) is exceeded. When the population density is low (feeding), the risk is low even at high sonar source levels and long-duration exercises (>24 h). With densely packed populations (overwintering), a sonar exercise might expose the entire population to levels >SEL(0) within a 24-h exercise period. However, the disturbance will be short and the response threshold used here is highly conservative. It is therefore unlikely that naval sonar will significantly impact the herring population.

  13. 78 FR 70567 - Nationwide Use of High Frequency and Ultra High Frequency Active SONAR Technology; Final...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-26

    ... Frequency (UHF) Sound Navigation and Ranging (SONAR) Technology and Finding of No Significant Impact (FONSI..., day or night regardless of visibility and in air and water temperatures and thermoclines normal...

  14. Obstacle avoidance sonar for submarines

    NASA Astrophysics Data System (ADS)

    Dugas, Albert C.; Webman, Kenneth M.

    2002-05-01

    The Advanced Mine Detection Sonar (AMDS) system was designed to operate in poor environments with high biological and/or shallow-water boundary conditions. It provides increased capability for active detection of volume, close-tethered, and bottom mines, as well as submarine and surface target active/passive detection for ASW and collision avoidance. It also provides bottom topography mapping capability for precise submarine navigation in uncharted littoral waters. It accomplishes this by using advanced processing techniques with extremely narrow beamwidths. The receive array consists of 36 modules arranged in a 15-ft-diameter semicircle at the bottom of the submarine sonar dome to form a chin-mounted array. Each module consists of 40 piezoelectric rubber elements. The modules provide the necessary signal conditioning to the element data prior to signal transmission (uplink) through the hull. The elements are amplified, filtered, converted to digital signals by an A/D converter, and multiplexed prior to uplink to the inboard receiver. Each module also has a downlink over which it receives synchronization and mode/gain control. Uplink and downlink transmission is done using fiberoptic telemetry. AMDS was installed on the USS Asheville. The high-frequency chin array for Virginia class submarines is based on the Asheville design.

  15. The effect of active sonar for the protection of moored and anchored warships on the human hearing.

    PubMed

    Salami, Angelo; Dellepiane, Massimo; Barbierato, Mauro; Freda, Pierluigi; Crippa, Barbara; Guastini, Luca; Mora, Renzo

    2010-02-01

    This study wants to show the effects of active middle frequency sonar on a selected group of Italian Navy divers. Ten male divers with normal hearing were exposed to active sonar of the Italian Navy for more than 100 exposures, each of at least 1-h duration, in the course of 6 months. Before, at the end, and six months after the end of noise exposure, we performed pure-tone audiometry, Carhart test, Peyser test, thresholds of discomfort test (TDT), tympanometry, transient evoked otoacoustic emissions (TEOAE), distortion product otoacoustic emissions (DPOAE), and auditory brainstem response (ABR). At the end of the noise exposure, the audiological tests showed a worsening of the mean air and bone audiometric thresholds at the 2,000 (1/10), 4,000 (7/10), and 8,000 Hz (6/10); a fail status of the TEOAE and DPOAE, which were previously present, in all the divers; temporary threshold shift, at the Peyser test, in 9/10 divers; discomfort for pulse tone presented at the TDT test, in all the divers; no post exposure significant differences at the Carhart and ABR tests, in any of the divers. Six months after the end of noise exposure, all the divers presented a complete recovery of their audio-vestibular functions. Our results show the temporary negative effects of repeated and lasting exposure to active sonar (Hull MF) on the divers; the last control demonstrate the absence of permanent noise-induced hearing loss in divers exposed to active sonar.

  16. Assessing Beaked Whale Reproduction and Stress Response Relative to Sonar Activity at the Atlantic Undersea Test and Evaluation Center (AUTEC)

    DTIC Science & Technology

    2011-09-30

    England. (2001) Joint interim report Bahamas marine mammal stranding event of 15 – 16 March 2000. National Oceanographic and Atmospheric Administration...Relative to Sonar Activity at the Atlantic Undersea Test and Evaluation Center (AUTEC) Diane Elaine Claridge Bahamas Marine Mammal Research...ADDRESS(ES) Bahamas Marine Mammal Research Organisation,P.O. Box AB-20714,Marsh Harbour,Abaco, Bahamas, 8. PERFORMING ORGANIZATION REPORT NUMBER 9

  17. Target-depth estimation in active sonar: Cramer-Rao bounds for a bilinear sound-speed profile.

    PubMed

    Mours, Alexis; Ioana, Cornel; Mars, Jérôme I; Josso, Nicolas F; Doisy, Yves

    2016-09-01

    This paper develops a localization method to estimate the depth of a target in the context of active sonar, at long ranges. The target depth is tactical information for both strategy and classification purposes. The Cramer-Rao lower bounds for the target position as range and depth are derived for a bilinear profile. The influence of sonar parameters on the standard deviations of the target range and depth are studied. A localization method based on ray back-propagation with a probabilistic approach is then investigated. Monte-Carlo simulations applied to a summer Mediterranean sound-speed profile are performed to evaluate the efficiency of the estimator. This method is finally validated on data in an experimental tank.

  18. Effects of surveillance towed array sensor system (SURTASS) low frequency active sonar on fish

    NASA Astrophysics Data System (ADS)

    Popper, Arthur N.; Halvorsen, Michele B.; Miller, Diane; Smith, Michael E.; Song, Jiakun; Wysocki, Lidia E.; Hastings, Mardi C.; Kane, Andrew S.; Stein, Peter

    2005-04-01

    We investigated the effects of exposure to Low Frequency Active (LFA) sonar on rainbow trout (a hearing non-specialist related to several endangered salmonids) and channel catfish (a hearing specialist), using an element of the standard SURTASS LFA source array. We measured hearing sensitivity using auditory brainstem response, effects on inner ear structure using scanning electron microscopy, effects on non-auditory tissues using general pathology and histopathology, and behavioral effects with video monitoring. Exposure to 193 dB re 1 microPa (rms received level) in the LFA frequency band for 324 seconds resulted in a TTS of 20 dB at 400 Hz in rainbow trout, with less TTS at 100 and 200 Hz. TTS in catfish ranged from 6 to 12 dB at frequencies from 200 to 1000 Hz. Both species recovered from hearing loss in several days. Inner ears sensory tissues appeared unaffected by acoustic exposure. Gross pathology indicated no damage to non-auditory tissues, including the swim bladder. Both species showed consistent startle responses at sound onsets and changed their position relative to the sound source during exposures. There was no fish death attributable to sound exposure even up to four days post-exposure. [Work supported by Chief of Naval Operations.

  19. Cetacean Social Behavioral Response to Sonar Exposure

    DTIC Science & Technology

    2015-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Cetacean social behavioral response to sonar exposure Dr...TERM GOALS The goal of this effort is to investigate cetacean social behavioral response to sonar signals. OBJECTIVES The scientific objectives...of this effort are to determine: 1) social behavioral responses of cetaceans to sonar and to tagging, to investigate the biological relevance and

  20. Signal analysis by means of time-frequency (Wigner-type) distributions -- Applications to sonar and radar echoes

    SciTech Connect

    Gaunaurd, G.; Strifors, H.C.

    1996-09-01

    Time series data have been traditionally analyzed in either the time or the frequency domains. For signals with a time-varying frequency content, the combined time-frequency (TF) representations, based on the Cohen class of (generalized) Wigner distributions (WD`s) offer a powerful analysis tool. Using them, it is possible to: (1) trace the time-evolution of the resonance features usually present in a standard sonar cross section (SCS), or in a radar cross section (RCS) and (2) extract target information that may be difficult to even notice in an ordinary SCS or RCS. After a brief review of the fundamental properties of the WD, the authors discuss ways to reduce or suppress the cross term interference that appears in the WD of multicomponent systems. These points are illustrated with a variety of three-dimensional (3-D) plots of Wigner and pseudo-Wigner distributions (PWD), in which the strength of the distribution is depicted as the height of a Wigner surface with height scales measured by various color shades or pseudocolors. The authors also review studies they have made of the echoes returned by conducting or dielectric targets in the atmosphere, when they are illuminated by broadband radar pings. A TF domain analysis of these impulse radar returns demonstrates their superior informative content. These plots allow the identification of targets in an easier and clearer fashion than by the conventional RCS of narrowband systems. The authors show computed and measured plots of WD and PWD of various types of aircraft to illustrate the classification advantages of the approach at any aspect angle. They also show analogous results for metallic objects buried underground, in dielectric media, at various depths.

  1. Classification of elastic objects by active sonar in the vicinity of shallow sea boundaries

    NASA Astrophysics Data System (ADS)

    Gaunaurd, Guillermo C.; Werby, Michael F.

    1992-09-01

    Active sonar classification of submerged elastic structures becomes increasingly difficult when the structure is close to the bottom or surface of the sea. The backscattering cross-section (BSCS) of any target, which is relatively simpler to determine in deep waters, away from boundaries, becomes substantially distorted as the structure approaches either one of these environmental boundaries. Near these interfaces the classification methodology based on echo resonances that we have used in the past (viz., Appl. Mechanics Reviews 43, 171-208, (1990)) can no longer be used. By means of the examples of a spherical shell and an elastic solid sphere insonified by plane waves, we study the above mentioned degradation in BSCS in order to assess how distant the structure should be from these boundaries before the resonance features become discernible again in the echoes, and object recognition is again possible. Our approach is based on the method of images for the construction of the appropriate Green's functions, combined with a very involved two-body scattering formulation that determines the combined T-Matrix of two insonified objects, when the T-Matrix of each individual object is known. The method is extended to the time domain. We present form-functions in the frequency domain, as well as late-time responses in the time domain for both sphere and shell as they approach the mentioned boundaries. Boundary effects seem to be confined to a 'skin layer' bounded by R

  2. Behavioral Response of Dolphins to Signals Simulating Mid-Frequency Sonar

    DTIC Science & Technology

    2010-09-30

    dose - response function (DRF) for delphinid and otariid species exposed to mid-frequency signals. 2) Record heart rate on a subset of the dolphins and sea lions involved in the behavioral response study to determine whether an acute stress response occurs in response to the mid-frequency sound exposure. The response will be related to the exposure characteristics of the sound received by the animal to determine if there is a relationship between the sound exposure and the magnitude and duration of the response. 3) Collect blood samples from a subset of the dolphins prior

  3. Automated Change Detection Using Synthetic Aperture Sonar Imagery

    DTIC Science & Technology

    2010-06-01

    using shadow outlining, scene matching using control-point matching, and visualization capabilities. This system was developed for sidescan sonar ...surveys using instrumentation such as the high-frequency Marine Sonic Technology sidescan sonar . In this paper, the authors describe modifications to...the sidescan -based system required to perform change detection using Synthetic Aperture Sonar (SAS) bottom imagery. Index Terms—Acoustic signal

  4. 3S(expn 2): Behavioral Response Studies of Cetaceans to Navy Sonar Signals in Norwegian Waters

    DTIC Science & Technology

    2013-09-30

    killer whale sounds; 2.) Conduct a directed study on the effectiveness of ramp-up as a mitigation method with abundant and relatively easy-to-study...The earlier 3S research effort (see related programs) with killer , sperm, and long-finned pilot whales provides a dataset that enables comparative...in order to identify response thresholds. Playback of killer whale sounds is conducted to assess how responses to sonar might be shaped by

  5. 3S(expn 2): Behavioral Response Studies of Cetaceans to Navy Sonar Signals in Norwegian Waters

    DTIC Science & Technology

    2011-09-30

    behavioral reactions and the sound exposures required to elicit them of three species of whales : bottlenose whales , minke whales , and humpback whales to Low... humpback whales . OBJECTIVES In this research project, our objectives are to: 1.) Expand our comparative experimental dataset to include species...and relatively easy-to-study humpback whales , Megaptera novaeangliae; 3.) Record sufficient no-sonar baseline data of all target species to adequately

  6. Aerial ultrasonic micro Doppler sonar detection range in outdoor environments.

    PubMed

    Bradley, Marshall; Sabatier, James M

    2012-03-01

    Current research demonstrates that micro Doppler sonar has the capability to uniquely identify the presence of a moving human, making it an attractive component in surveillance systems for border security applications. Primary environmental factors that limit sonar performance are two-way spreading losses, ultrasonic absorption, and backscattered energy from the ground that appears at zero Doppler shift in the sonar signal processor. Spectral leakage from the backscatter component has a significant effect on sonar performance for slow moving targets. Sonar performance is shown to rapidly decay as the sensor is moved closer to the ground due to increasing surface backscatter levels.

  7. Digitally controlled sonars

    NASA Technical Reports Server (NTRS)

    Hansen, G. R.

    1983-01-01

    Sonars are usually designed and constructed as stand alone instruments. That is, all elements or subsystems of the sonar are provided: power conditioning, displays, intercommunications, control, receiver, transmitter, and transducer. The sonars which are a part of the Advanced Ocean Test Development Platform (AOTDP) represent a departure from this manner of implementation and are configured more like an instrumentation system. Only the transducer, transmitter, and receiver which are unique to a particular sonar function; Up, Down, Side Scan, exist as separable subsystems. The remaining functions are reserved to the AOTDP and serve all sonars and other instrumentation in a shared manner. The organization and functions of the common AOTDP elements were described and then the interface with the sonars discussed. The techniques for software control of the sonar parameters were explained followed by the details of the realization of the sonar functions and some discussion of the performance of the side scan sonars.

  8. An Improved Azimuth Angle Estimation Method with a Single Acoustic Vector Sensor Based on an Active Sonar Detection System.

    PubMed

    Zhao, Anbang; Ma, Lin; Ma, Xuefei; Hui, Juan

    2017-02-20

    In this paper, an improved azimuth angle estimation method with a single acoustic vector sensor (AVS) is proposed based on matched filtering theory. The proposed method is mainly applied in an active sonar detection system. According to the conventional passive method based on complex acoustic intensity measurement, the mathematical and physical model of this proposed method is described in detail. The computer simulation and lake experiments results indicate that this method can realize the azimuth angle estimation with high precision by using only a single AVS. Compared with the conventional method, the proposed method achieves better estimation performance. Moreover, the proposed method does not require complex operations in frequencydomain and achieves computational complexity reduction.

  9. An Improved Azimuth Angle Estimation Method with a Single Acoustic Vector Sensor Based on an Active Sonar Detection System

    PubMed Central

    Zhao, Anbang; Ma, Lin; Ma, Xuefei; Hui, Juan

    2017-01-01

    In this paper, an improved azimuth angle estimation method with a single acoustic vector sensor (AVS) is proposed based on matched filtering theory. The proposed method is mainly applied in an active sonar detection system. According to the conventional passive method based on complex acoustic intensity measurement, the mathematical and physical model of this proposed method is described in detail. The computer simulation and lake experiments results indicate that this method can realize the azimuth angle estimation with high precision by using only a single AVS. Compared with the conventional method, the proposed method achieves better estimation performance. Moreover, the proposed method does not require complex operations in frequency-domain and achieves computational complexity reduction. PMID:28230763

  10. Effect of level, duration, and inter-pulse interval of 1-2 kHz sonar signal exposures on harbor porpoise hearing.

    PubMed

    Kastelein, Ronald A; Hoek, Lean; Gransier, Robin; Rambags, Martijn; Claeys, Naomi

    2014-07-01

    Safety criteria for underwater low-frequency active sonar sounds produced during naval exercises are needed to protect harbor porpoise hearing. As a first step toward defining criteria, a porpoise was exposed to sequences consisting of series of 1-s, 1-2 kHz sonar down-sweeps without harmonics (as fatiguing noise) at various combinations of average received sound pressure levels (SPLs; 144-179 dB re 1 μPa), exposure durations (1.9-240 min), and duty cycles (5%-100%). Hearing thresholds were determined for a narrow-band frequency-swept sine wave centered at 1.5 kHz before exposure to the fatiguing noise, and at 1-4, 4-8, 8-12, 48, 96, 144, and 1400 min after exposure, to quantify temporary threshold shifts (TTSs) and recovery of hearing. Results show that the inter-pulse interval of the fatiguing noise is an important parameter in determining the magnitude of noise-induced TTS. For the reported range of exposure combinations (duration and SPL), the energy of the exposure (i.e., cumulative sound exposure level; SELcum) can be used to predict the induced TTS, if the inter-pulse interval is known. Exposures with equal SELcum but with different inter-pulse intervals do not result in the same induced TTS.

  11. Source ranging with an underwater geographic point in non-cooperative bistatic sonar

    NASA Astrophysics Data System (ADS)

    Lee, Donghwa; Jung, Tae Jin; Lee, Kyun Kyung; Myung, Hyun

    2014-01-01

    Active sonar is divided into monostatic and bistatic sonar according to the relative positions of the source and the receiver. Bistatic sonar on modern submarines is classified into cooperative and non-cooperative operations. Cooperative operation uses an active signal of a friendly ship; therefore, source information is known a priori, whereas non-cooperative operation utilizes an active signal of the enemy, and hence, it is difficult to acquire source information, such as a source range, which is important for bistatic sonar operation. In order to overcome this difficulty, this paper proposes an estimation method for the source range that employs geographic information, and the utility of the source range estimation is evaluated. For the evaluation, we consider three error components. Then, the validity of the scheme is confirmed through theoretical error analysis and simulation study. The results show that geographic points that satisfy certain specific conditions can be used to estimate the source range within a range of tens of km in the simulation. Finally, we confirm that the receiver could estimate the source range from far away using non-cooperative bistatic sonar.

  12. Sonar array processing borrows from geophysics

    SciTech Connect

    Chen, K.

    1989-09-01

    The author reports a recent advance in sonar signal processing that has potential military application. It improves signal extraction by modifying a technique devised by a geophysicist. Sonar signal processing is used to track submarine and surface targets, such as aircraft carriers, oil tankers, and, in commercial applications, schools of fish or sunken treasure. Similar signal-processing techniques help radio astronomers track galaxies, physicians see images of the body interior, and geophysicists map the ocean floor or find oil. This hydrid technique, applied in an experimental system, can help resolve strong signals as well as weak ones in the same step.

  13. Imaging Active and Relict Seafloor Methane Seep Sites: a Comparison of Seafloor 3D Seismic Reflectivity and Multibeam Sonar Backscatter Intensity at Omakere Ridge, Hikurangi Margin, New Zealand

    NASA Astrophysics Data System (ADS)

    Golding, T. V.; Pecher, I. A.; Crutchley, G. J.; Klaeschen, D.; Papenberg, C. A.; Bialas, J.; Greinert, J.; Townend, J.; SO214 Shipboard Scientific Party

    2011-12-01

    Omakere Ridge is an anticlinal thrust ridge in water depths of 1100-1700 m on the Hikurangi Margin, east of the North Island of New Zealand, and an area of active seafloor methane seepage associated with an extensive gas hydrate province. Methane seep sites on the Hikurangi Margin are characterised by localised build-ups of hard authigenic carbonate and chemosynthetic seep fauna that exist on a seafloor otherwise characterised by soft, muddy sediments. Previous studies have shown that these seep sites appear as areas of high backscatter in sonar images, but backscatter data alone do not provide detailed information on the present level of activity of a seep site, or the thickness of the carbonate build-up. Here we present a comparison of seafloor seismic reflectivity and multibeam sonar backscatter intensity data collected from active and relict methane seep sites on Omakere Ridge. High-resolution P-Cable 3D seismic reflection data and 12 kHz EM120 multibeam sonar data were collected in March 2011 during the RV Sonne cruise SO214. Seafloor seismic amplitude maps have been derived from the shipboard post-stack migrated data cube. A pronounced acquisition artifact is manifest in the seafloor horizon slice as high and low amplitude stripes that alternate periodically in the crossline direction. We have removed this artifact from the seafloor horizon slice using Kx-Ky filtering, followed by direct sampling and deterministic removal of the very-low-frequency components in the spatial domain. The seismic amplitude map has then been transformed into a calibrated seafloor reflection coefficient map. Sonar backscatter mosaics have been created after correcting for instrument response, angular variation in backscatter and bathymetry. Several backscatter mosaics were incorporated into a stacked mosaic over the study area to attenuate random noise. The high sonar backscatter response at the seep sites is generally accompanied by high seismic reflectivity. However, the

  14. Active part of Charlie--Gibbs fracture zone: A study using sonar and other geophysical techniques

    SciTech Connect

    Searle, R.

    1981-01-10

    A short survey with Gloria side-scan sonar and other geophysical instruments has revealed new information about Charlie--Gibbs fracture zone between 29/sup 0/ and 36 /sup 0/W. The traces of two transform faults have been clearly delineated. They fit small circles about the pole of rotation with an rms error of only about 1 km, but they do not always follow the deepest parts of the transform valleys. The transforms are joined by a short spreading center at 31 /sup 0/45 'W. The median transverse ridge appears to have been produced by normal seafloor spreading at this center and bears identifiable Vine-Matthews magnetic anomalies. A transverse ridge along the eastern inactive part of the northern transform may be an intrusive feature. Considerable thickness of sediment appear to have been deposited in the northern transform valley from Norwegian Sea overflow water passing through the fracture zone, but transverse ridges have prevented the sediment reaching the southern valley.

  15. Bearing Estimation Uncertainties for the Volume Search Sonar

    DTIC Science & Technology

    2009-08-31

    II bathymetric sidescan sonar system”, IEEE Journal of Oceanic Engineering, 17(3), 239-251, 1992. R. O. Nielsen, “Accuracy of angle estimation with...shows potential for detecting variations in sediment type in much the same manner that a sidescan sonar detects these variations. However, this data...code) 31/08/2009 Final / Technical 2003 - Aug. 2008 Acoustic Signal Processing for Ocean Mapping Applications With The Volume Search Sonar (VSS

  16. Performance and Preference on a Sonar Detection Task under Various Colors of Ambient Illumination

    DTIC Science & Technology

    1984-05-17

    fine acuity , color vision, and dark adaptation. Due to the additional advantages of subdued white illumination, it is recommended for use in sonar...sonar systems of the increase in the number of provided primarily auditory signals visual displays. The change to for the cperator to use in the blue, in...which tried blue was so much more important than the sleeves over the light bulbs in the visual , lighting in the sonar shack sonar control room and

  17. Mitigation Modelling of the Leeuwin Class Hydrographic Sonars in Shoalwater Bay

    DTIC Science & Technology

    2009-12-01

    The welfare of dolphins and dugongs is the main concern in Shoalwater Bay in reference to hydrographic sonar frequencies. Modelling therefore...considered all sonars capable of radiating signals within the auditory frequency range of dolphins, 1 to 150 kHz, and dugongs , 1 to 8 kHz. Sonar operations...at frequencies above 200 kHz were not considered since the effects on dolphins and dugongs were assumed inconsequential. The sonar with the lowest

  18. Navigation Hazard Survey Sonar.

    DTIC Science & Technology

    1982-04-01

    NSTL Station, Miss., NORDA Technical Note 17. Flemming, B.W. (1976). Side Scan Sonar: A Practical Guide. Int. Hydrog . Rev., 53(1), p. 65-92. Harris...Corporation, Harris Division, Westwoo, Mass., 02090, manufacturer brochure. Leenhardt, 0. (1975). Side canning Sonar -- A Theoretical Study. Int. Hydrog . Rev

  19. A Robust and Fast Method for Sidescan Sonar Image Segmentation Using Nonlocal Despeckling and Active Contour Model.

    PubMed

    Huo, Guanying; Yang, Simon X; Li, Qingwu; Zhou, Yan

    2017-04-01

    Sidescan sonar image segmentation is a very important issue in underwater object detection and recognition. In this paper, a robust and fast method for sidescan sonar image segmentation is proposed, which deals with both speckle noise and intensity inhomogeneity that may cause considerable difficulties in image segmentation. The proposed method integrates the nonlocal means-based speckle filtering (NLMSF), coarse segmentation using k -means clustering, and fine segmentation using an improved region-scalable fitting (RSF) model. The NLMSF is used before the segmentation to effectively remove speckle noise while preserving meaningful details such as edges and fine features, which can make the segmentation easier and more accurate. After despeckling, a coarse segmentation is obtained by using k -means clustering, which can reduce the number of iterations. In the fine segmentation, to better deal with possible intensity inhomogeneity, an edge-driven constraint is combined with the RSF model, which can not only accelerate the convergence speed but also avoid trapping into local minima. The proposed method has been successfully applied to both noisy and inhomogeneous sonar images. Experimental and comparative results on real and synthetic sonar images demonstrate that the proposed method is robust against noise and intensity inhomogeneity, and is also fast and accurate.

  20. Application of the T-Matrix Method to the Numerical Modeling of a Linear Active Sonar Array

    DTIC Science & Technology

    2013-06-01

    5 2.1 COMSOL Finite Element Analysis . . . . . . . . . . . . . . . . . . . 5 2.2 Piezoelectric Spherical Thin-Shell Transducer...maximize the directionality and steer optimum acoustic beams . Figure 1.1 shows two examples of volumetric sonar array applications. (a) (b) Figure 1.1...single-transducer, from such as a finite -element model (FEM). This thesis focuses on building a three- dimensional (3D) FEM of a volumetric

  1. Measurement of fish movements at depths to 6000 m using a deep-ocean lander incorporating a short base-line sonar utilizing miniature code-activated transponder technology

    NASA Astrophysics Data System (ADS)

    Bagley, P. M.; Bradley, S.; Priede, I. G.; Gray, P.

    1999-12-01

    Most research on animal behaviour in the deep ocean (to depths of 6000 m) is restricted to the capture of dead specimens or viewing activity over small areas of the sea floor by means of cameras or submersibles. This paper describes the use of a miniature acoustic code-activated transponder (CAT) tag and short base-line sonar to track the movements of deep-sea fish in two dimensions over an area 1 km in diameter centred on a lander platform. The CAT tags and sonar are transported to the deep-sea floor by means of a subsea mooring which is ballasted so that it lands and remains on the sea floor for the duration of the tracking experiment (the lander). A description of the CAT, lander and short base-line sonar is given. Results are presented to illustrate the operation of the system.

  2. Offshore exploration and platform siting by imaging Sonar

    SciTech Connect

    Feder, A.M.

    1986-03-17

    Sonar, an acronym for sonic azimuth and ranging (some say ''sonic detection and ranging''), is the name of a type of remote sensor that was developed in World War II for antisubmarine warfare purposes. The principles of the sensor system are simple in that it broadcasts a focused (shaped) sonic pulse through the water (transmission medium), then receives the echo of that pulse and processes this signal for its information content. Hence, Sonar system principles are highly analagous to those of radar. Post-World War II saw development of Sonar probes that provided some success in determining sea floor materials composition and condition (e.g., subbottom profilers). The major advance, however, was with the advent of digital computation systems. These permitted the coupling of Sonar azimuth and range components to provide ''x'' and ''y'' coordinates for each echo location, or ''z'' value. This advance is seeing a proliferation of different types of imaging Sonar systems and performances.

  3. Acylcarnitines activate proinflammatory signaling pathways.

    PubMed

    Rutkowsky, Jennifer M; Knotts, Trina A; Ono-Moore, Kikumi D; McCoin, Colin S; Huang, Shurong; Schneider, Dina; Singh, Shamsher; Adams, Sean H; Hwang, Daniel H

    2014-06-15

    Incomplete β-oxidation of fatty acids in mitochondria is a feature of insulin resistance and type 2 diabetes mellitus (T2DM). Previous studies revealed that plasma concentrations of medium- and long-chain acylcarnitines (by-products of incomplete β-oxidation) are elevated in T2DM and insulin resistance. In a previous study, we reported that mixed D,L isomers of C12- or C14-carnitine induced an NF-κB-luciferase reporter gene in RAW 264.7 cells, suggesting potential activation of proinflammatory pathways. Here, we determined whether the physiologically relevant L-acylcarnitines activate classical proinflammatory signaling pathways and if these outcomes involve pattern recognition receptor (PRR)-associated pathways. Acylcarnitines induced the expression of cyclooxygenase-2 in a chain length-dependent manner in RAW 264.7 cells. L-C14 carnitine (5-25 μM), used as a representative acylcarnitine, stimulated the expression and secretion of proinflammatory cytokines in a dose-dependent manner. Furthermore, L-C14 carnitine induced phosphorylation of JNK and ERK, common downstream components of many proinflammatory signaling pathways including PRRs. Knockdown of MyD88, a key cofactor in PRR signaling and inflammation, blunted the proinflammatory effects of acylcarnitine. While these results point to potential involvement of PRRs, L-C14 carnitine promoted IL-8 secretion from human epithelial cells (HCT-116) lacking Toll-like receptors (TLR)2 and -4, and did not activate reporter constructs in TLR overexpression cell models. Thus, acylcarnitines have the potential to activate inflammation, but the specific molecular and tissue target(s) involved remain to be identified.

  4. Acylcarnitines activate proinflammatory signaling pathways

    PubMed Central

    Rutkowsky, Jennifer M.; Knotts, Trina A.; Ono-Moore, Kikumi D.; McCoin, Colin S.; Huang, Shurong; Schneider, Dina; Singh, Shamsher; Hwang, Daniel H.

    2014-01-01

    Incomplete β-oxidation of fatty acids in mitochondria is a feature of insulin resistance and type 2 diabetes mellitus (T2DM). Previous studies revealed that plasma concentrations of medium- and long-chain acylcarnitines (by-products of incomplete β-oxidation) are elevated in T2DM and insulin resistance. In a previous study, we reported that mixed d,l isomers of C12- or C14-carnitine induced an NF-κB-luciferase reporter gene in RAW 264.7 cells, suggesting potential activation of proinflammatory pathways. Here, we determined whether the physiologically relevant l-acylcarnitines activate classical proinflammatory signaling pathways and if these outcomes involve pattern recognition receptor (PRR)-associated pathways. Acylcarnitines induced the expression of cyclooxygenase-2 in a chain length-dependent manner in RAW 264.7 cells. l-C14 carnitine (5–25 μM), used as a representative acylcarnitine, stimulated the expression and secretion of proinflammatory cytokines in a dose-dependent manner. Furthermore, l-C14 carnitine induced phosphorylation of JNK and ERK, common downstream components of many proinflammatory signaling pathways including PRRs. Knockdown of MyD88, a key cofactor in PRR signaling and inflammation, blunted the proinflammatory effects of acylcarnitine. While these results point to potential involvement of PRRs, l-C14 carnitine promoted IL-8 secretion from human epithelial cells (HCT-116) lacking Toll-like receptors (TLR)2 and -4, and did not activate reporter constructs in TLR overexpression cell models. Thus, acylcarnitines have the potential to activate inflammation, but the specific molecular and tissue target(s) involved remain to be identified. PMID:24760988

  5. Cetaceans and Naval Sonar: Behavioral Response as a Function of Sonar Frequency

    DTIC Science & Technology

    2011-09-30

    Nowacek, D. P., Thorne , L. H., Johnston, D. W., Tyack, P. L. 2007. Responses of cetaceans to anthropogenic noise. Mammal Review 37, 81-115...Tyack PL, Bird A, Miller PJO. (submitted) Vocal matching of sonar signals by long-finned pilot whales (Globicephala melas). Naturwissenschaften

  6. Spatial perception and adaptive sonar behavior.

    PubMed

    Aytekin, Murat; Mao, Beatrice; Moss, Cynthia F

    2010-12-01

    Bat echolocation is a dynamic behavior that allows for real-time adaptations in the timing and spectro-temporal design of sonar signals in response to a particular task and environment. To enable detailed, quantitative analyses of adaptive sonar behavior, echolocation call design was investigated in big brown bats, trained to rest on a stationary platform and track a tethered mealworm that approached from a starting distance of about 170 cm in the presence of a stationary sonar distracter. The distracter was presented at different angular offsets and distances from the bat. The results of this study show that the distance and the angular offset of the distracter influence sonar vocalization parameters of the big brown bat, Eptesicus fuscus. Specifically, the bat adjusted its call duration to the closer of two objects, distracter or insect target, and the magnitude of the adjustment depended on the angular offset of the distracter. In contrast, the bat consistently adjusted its call rate to the distance of the insect, even when this target was positioned behind the distracter. The results hold implications for understanding spatial information processing and perception by echolocation.

  7. Multiple Frequency Parametric Sonar

    DTIC Science & Technology

    2015-09-28

    300003 1 MULTIPLE FREQUENCY PARAMETRIC SONAR STATEMENT OF GOVERNMENT INTEREST [0001] The invention described herein may be manufactured and...beams. However, the multiple nonlinear interactions are not taken advantage of in order to generate additional efficiencies, bandwidth, and SNR...array. [0050] It will be understood that many additional changes in details, materials , steps, and arrangements of parts which have been described

  8. Ceteacean Social Behavioral Response to Sonar

    DTIC Science & Technology

    2013-09-30

    responses to sonar signals and other stimuli (tagging effort, killer whale playbacks) as well as baseline behavior, are studied within the larger... killer whale vocalizations in 3S2 - Response to tagging and vessel noise exposure in Azores-Baseline - Species: Northern bottlenose whale , Risso’s...common dolphin, bottlenose dolphin, killer whale  Cross-study implementation of group sampling methodology - Protocols used in four BRS studies

  9. Parametric sonars for seafloor characterization

    NASA Astrophysics Data System (ADS)

    Caiti, Andrea; Bergem, Oddbjorn; Dybedal, Johnny

    1999-12-01

    Parametric sonars are instruments capable of transmitting acoustic signals in the water with a very narrow beam and almost no sidelobes. These features are exploited in this paper to define a methodology for quantitative estimation of the geo-acoustic and morphological properties of the uppermost seafloor sediment layer. The three major components of the approach are the parametric instrument itself; the modelling of the forward-propagation problem, with the use of the Kirchhoff approximation for surface scattering and of the small-perturbation theory for the volume scattering; and the definition of a criterion for comparison between data and model predictions, which is accomplished by a generalized time-frequency analysis. In this way the estimation becomes one of a model-based identification, or a model-based inverse problem. Results from a field trial in a shallow water area of the Mediterranean are shown, and compared with independently gathered ground truth.

  10. Principles of Sonar Installation

    DTIC Science & Technology

    1982-01-26

    4) sonar release mechanisms, (5) fish finders, (6) counter«; and trackers, and (7) telemetry systems that use acoustic beams in- stead of wire ...multiplexing (CDM). When multiplexing is not employed, a pair of twisted wires is used for each hydrophone but the method creates a very bulky cable ...the necessity of auxiliary beamforming electronics . A typical beam pattern is shown in figure 1.48; it was obtained Figure 1.47. Focusing using a

  11. Phase sensitivity in bat sonar revisited.

    PubMed

    Schörnich, Sven; Wiegrebe, Lutz

    2008-01-01

    An echolocating bat produces echoes consisting of the convolution of echolocation call and the impulse response (IR) of the ensonified object. A crucial question in animal sonar is whether bats are able to extract this IR from the echo. The bat inner ear generates a frequency representation of call and echo and IR extraction in the frequency domain requires accurate analysis of both magnitude and phase information. Previous studies investigating the phase sensitivity of bats using a jitter paradigm reported a temporal acuity down to 10 ns, suggesting perfect sonar phase representation. In a phantom-target playback experiment, we investigate the perceptual phase sensitivity of the bat Phyllostomus discolor using a novel approach: instead of manipulating IR phase by changing IR delay (jitter paradigm), we randomized IR phase and thus lengthened the IR over time, leaving the magnitude spectrum unchanged. Our results show that phase sensitivity, as reflected in the analysis of signal duration, appears to be much lower than phase sensitivity, as reflected in the analysis of signal onset. The current data indicate that different temporal aspects of sonar processing are encoded with very different temporal resolution and thus an overall claim of "phase sensitivity" as such cannot be maintained.

  12. Observing Ocean Ecosystems with Sonar

    SciTech Connect

    Matzner, Shari; Maxwell, Adam R.; Ham, Kenneth D.; Hytnen, Ross D.; Horne, John

    2016-12-01

    We present a real-time processing system for sonar to detect and track animals, and to extract water column biomass statistics in order to facilitate continuous monitoring of an underwater environment. The Nekton Interaction Monitoring System (NIMS) is built to connect to an instrumentation network, where it consumes a real-time stream of sonar data and archives tracking and biomass data.

  13. Signaling during platelet adhesion and activation

    PubMed Central

    Li, Zhenyu; Delaney, M. Keegan; O’Brien, Kelly A.; Du, Xiaoping

    2011-01-01

    Upon vascular injury, platelets are activated by adhesion to adhesive proteins like von Willebrand factor and collagen, or by soluble platelet agonists like ADP, thrombin, and thromboxane A2. These adhesive proteins and soluble agonists induce signal transduction via their respective receptors. The various receptor-specific platelet activation signaling pathways converge into common signaling events, which stimulate platelet shape change, granule secretion, and ultimately induce the “inside-out” signaling process leading to activation of the ligand binding function of integrin αIIbβ3. Ligand binding to integrin αIIbβ3 mediates platelet adhesion and aggregation and triggers “outside-in” signaling, resulting in platelet spreading, additional granule secretion, stabilization of platelet adhesion and aggregation, and clot retraction. It has become increasingly evident that agonist-induced platelet activation signals also crosstalk with integrin “outside-in” signals to regulate platelet responses. Platelet activation involves a series of rapid positive feedback loops that greatly amplify initial activation signals, and enable robust platelet recruitment and thrombus stabilization. Recent studies have provided novel insight into the molecular mechanisms of these processes. PMID:21071698

  14. CDPK Activation in PRR Signaling.

    PubMed

    Seybold, Heike; Boudsocq, Marie; Romeis, Tina

    2017-01-01

    Calcium-dependent protein kinases undergo a rapid biochemical activation in response to an intracellular Ca increase induced by the PRR-dependent perception of a pathogen-related stimulus. Based on SDS gel resolution, the in-gel kinase assay allows the analysis of multiple in vivo protein samples in parallel, combining the advantage of protein separation according to molecular mass with the activity read-out of a protein kinase assay. It thus enables to follow the transient CDPK activation and inactivation in response to in vivo elicitation with a time-wise resolution. In addition, changes of CDPK phosphorylation activity often correlate with slight shifts in the enzyme's apparent molecular mass, indicating posttranslational modifications and a conformational change of the active enzyme compared to its inactive resting form. These band shifts can be detected by a simple immunoblotting to monitor CDPK activation.

  15. Phase calibration of sonar systems using standard targets and dual-frequency transmission pulses.

    PubMed

    Islas-Cital, Alan; Atkins, Philip R; Foo, Kae Y; Picó, Ruben

    2011-10-01

    The phase angle component of the complex frequency response of a sonar system operating near transducer resonance is usually distorted. Interpretation and classification of the received sonar signal benefits from the preservation of waveform fidelity over the full bandwidth. A calibration process that measures the phase response in addition to the amplitude response is thus required. This paper describes an extension to the standard-target calibration method to include phase angle, without affecting the experimental apparatus, by using dual-frequency transmission pulses and frequency-domain data processing. This approach reduces the impact of unknown range and sound speed parameters upon phase calibration accuracy, as target phase is determined from the relationship of the two frequency components instead of relying on a local phase reference. Tungsten carbide spheres of various sizes were used to simultaneously calibrate the amplitude and phase response of an active sonar system in a laboratory tank. Experimental measurements of target phase spectra are in good agreement with values predicted from a theoretical model based upon full-wave analysis, over an operating frequency of 50-125 kHz.

  16. Sonar Locator Systems

    NASA Technical Reports Server (NTRS)

    1985-01-01

    An underwater locator device called a Pinger is attached to an airplane's flight recorder for recovery in case of a crash. Burnett Electronics Pinger Model 512 resulted from a Burnett Electronics Laboratory, Inc./Langley Research Center contract for development of a search system for underwater mines. The Pinger's battery-powered transmitter is activated when immersed in water, and sends multidirectional signals for up to 500 hours. When a surface receiver picks up the signal, a diver can retrieve the pinger and the attached airplane flight recorder. Other pingers are used to track whales, mark underwater discoveries and assist oil drilling vessels.

  17. A micro-Doppler sonar for acoustic surveillance in sensor networks

    NASA Astrophysics Data System (ADS)

    Zhang, Zhaonian

    Wireless sensor networks have been employed in a wide variety of applications, despite the limited energy and communication resources at each sensor node. Low power custom VLSI chips implementing passive acoustic sensing algorithms have been successfully integrated into an acoustic surveillance unit and demonstrated for detection and location of sound sources. In this dissertation, I explore active and passive acoustic sensing techniques, signal processing and classification algorithms for detection and classification in a multinodal sensor network environment. I will present the design and characterization of a continuous-wave micro-Doppler sonar to image objects with articulated moving components. As an example application for this system, we use it to image gaits of humans and four-legged animals. I will present the micro-Doppler gait signatures of a walking person, a dog and a horse. I will discuss the resolution and range of this micro-Doppler sonar and use experimental results to support the theoretical analyses. In order to reduce the data rate and make the system amenable to wireless sensor networks, I will present a second micro-Doppler sonar that uses bandpass sampling for data acquisition. Speech recognition algorithms are explored for biometric identifications from one's gait, and I will present and compare the classification performance of the two systems. The acoustic micro-Doppler sonar design and biometric identification results are the first in the field as the previous work used either video camera or microwave technology. I will also review bearing estimation algorithms and present results of applying these algorithms for bearing estimation and tracking of moving vehicles. Another major source of the power consumption at each sensor node is the wireless interface. To address the need of low power communications in a wireless sensor network, I will also discuss the design and implementation of ultra wideband transmitters in a three dimensional

  18. Security sonar for water intakes

    SciTech Connect

    Rothenbuhler, D.E.

    1987-07-01

    The security of the water approaches to nuclear facilities has been largely neglected because of the lack of solutions to the intrusion problem. This paper reviews underwater scanning sonar in general, highlights a number of problems encountered in a threat detection system using sonar and suggests some procedures that can help make such a system workable. Information is drawn from recent experience with several security projects in the governmental and private sectors, one of which was a nuclear facility.

  19. Bats coordinate sonar and flight behavior as they forage in open and cluttered environments.

    PubMed

    Falk, Benjamin; Jakobsen, Lasse; Surlykke, Annemarie; Moss, Cynthia F

    2014-12-15

    Echolocating bats use active sensing as they emit sounds and listen to the returning echoes to probe their environment for navigation, obstacle avoidance and pursuit of prey. The sensing behavior of bats includes the planning of 3D spatial trajectory paths, which are guided by echo information. In this study, we examined the relationship between active sonar sampling and flight motor output as bats changed environments from open space to an artificial forest in a laboratory flight room. Using high-speed video and audio recordings, we reconstructed and analyzed 3D flight trajectories, sonar beam aim and acoustic sonar emission patterns as the bats captured prey. We found that big brown bats adjusted their sonar call structure, temporal patterning and flight speed in response to environmental change. The sonar beam aim of the bats predicted the flight turn rate in both the open room and the forest. However, the relationship between sonar beam aim and turn rate changed in the forest during the final stage of prey pursuit, during which the bat made shallower turns. We found flight stereotypy developed over multiple days in the forest, but did not find evidence for a reduction in active sonar sampling with experience. The temporal patterning of sonar sound groups was related to path planning around obstacles in the forest. Together, these results contribute to our understanding of how bats coordinate echolocation and flight behavior to represent and navigate their environment.

  20. Bats coordinate sonar and flight behavior as they forage in open and cluttered environments

    PubMed Central

    Falk, Benjamin; Jakobsen, Lasse; Surlykke, Annemarie; Moss, Cynthia F.

    2014-01-01

    Echolocating bats use active sensing as they emit sounds and listen to the returning echoes to probe their environment for navigation, obstacle avoidance and pursuit of prey. The sensing behavior of bats includes the planning of 3D spatial trajectory paths, which are guided by echo information. In this study, we examined the relationship between active sonar sampling and flight motor output as bats changed environments from open space to an artificial forest in a laboratory flight room. Using high-speed video and audio recordings, we reconstructed and analyzed 3D flight trajectories, sonar beam aim and acoustic sonar emission patterns as the bats captured prey. We found that big brown bats adjusted their sonar call structure, temporal patterning and flight speed in response to environmental change. The sonar beam aim of the bats predicted the flight turn rate in both the open room and the forest. However, the relationship between sonar beam aim and turn rate changed in the forest during the final stage of prey pursuit, during which the bat made shallower turns. We found flight stereotypy developed over multiple days in the forest, but did not find evidence for a reduction in active sonar sampling with experience. The temporal patterning of sonar sound groups was related to path planning around obstacles in the forest. Together, these results contribute to our understanding of how bats coordinate echolocation and flight behavior to represent and navigate their environment. PMID:25394632

  1. Quantifying methane flux from lake sediments using multibeam sonar

    NASA Astrophysics Data System (ADS)

    Scandella, B.; Urban, P.; Delwiche, K.; Greinert, J.; Hemond, H.; Ruppel, C. D.; Juanes, R.

    2013-12-01

    Methane is a potent greenhouse gas, and the production and emission of methane from sediments in wetlands, lakes and rivers both contributes to and may be exacerbated by climate change. In some of these shallow-water settings, methane fluxes may be largely controlled by episodic venting that can be triggered by drops in hydrostatic pressure. Even with better constraints on the mechanisms for gas release, quantifying these fluxes has remained a challenge due to rapid spatiotemporal changes in the patterns of bubble emissions from the sediments. The research presented here uses a fixed-location Imagenex DeltaT 837B multibeam sonar to estimate methane-venting fluxes from organic-rich lake sediments over a large area (~400 m2) and over a multi-season deployment period with unprecedented spatial and temporal resolution. Simpler, single-beam sonar systems have been used in the past to estimate bubble fluxes in a variety of settings. Here we extend this methodology to a multibeam system by means of: (1) detailed calibration of the sonar signal against imposed bubble streams, and (2) validation against an in situ independent record of gas flux captured by overlying bubble traps. The calibrated sonar signals then yield estimates of the methane flux with high spatial resolution (~1 m) and temporal frequency (6 Hz) from a portion of the deepwater basin of Upper Mystic Lake, MA, USA, a temperate eutrophic kettle lake. These results in turn inform mathematical models of methane transport and release from the sediments, which reproduce with high fidelity the ebullitive response to hydrostatic pressure variations. In addition, the detailed information about spatial variability of methane flux derived from sonar records is used to estimate the uncertainty associated with upscaling flux measurements from bubble traps to the scale of the sonar observation area. Taken together, these multibeam sonar measurements and analysis provide a novel quantitative approach for the assessment of

  2. Scaffolds are 'active' regulators of signaling modules.

    PubMed

    Alexa, Anita; Varga, János; Reményi, Attila

    2010-11-01

    Signaling cascades, in addition to proteins with obvious signaling-relevant activities (e.g. protein kinases or receptors), also employ dedicated 'inactive' proteins whose functions appear to be the organization of the former components into higher order complexes through protein-protein interactions. The core function of signaling adaptors, anchors and scaffolds is the recruitment of proteins into one macromolecular complex. Several recent studies have demonstrated that the recruiter and the recruited molecules mutually influence each other in a scaffolded complex. This yields fundamentally novel properties for the signaling complex as a whole. Because these are not merely additive to the properties of the individual components, scaffolded signaling complexes may behave as functionally distinct modules.

  3. Sperm whales reduce foraging effort during exposure to 1-2 kHz sonar and killer whale sounds.

    PubMed

    Isojunno, Saana; Cure, Charlotte; Kvadsheim, Petter Helgevold; Lam, Frans-Peter Alexander; Tyack, Peter Lloyd; Wensveen, Paul Jacobus; Miller, Patrick James O'Malley

    2016-01-01

    The time and energetic costs of behavioral responses to incidental and experimental sonar exposures, as well as control stimuli, were quantified using hidden state analysis of time series of acoustic and movement data recorded by tags (DTAG) attached to 12 sperm whales (Physeter macrocephalus) using suction cups. Behavioral state transition modeling showed that tagged whales switched to a non-foraging, non-resting state during both experimental transmissions of low-frequency active sonar from an approaching vessel (LFAS; 1-2 kHz, source level 214 dB re 1 µPa m, four tag records) and playbacks of potential predator (killer whale, Orcinus orca) sounds broadcast at naturally occurring sound levels as a positive control from a drifting boat (five tag records). Time spent in foraging states and the probability of prey capture attempts were reduced during these two types of exposures with little change in overall locomotion activity, suggesting an effect on energy intake with no immediate compensation. Whales switched to the active non-foraging state over received sound pressure levels of 131-165 dB re 1 µPa during LFAS exposure. In contrast, no changes in foraging behavior were detected in response to experimental negative controls (no-sonar ship approach or noise control playback) or to experimental medium-frequency active sonar exposures (MFAS; 6-7 kHz, source level 199 re 1 µPa m, received sound pressure level [SPL] = 73-158 dB re 1 µPa). Similarly, there was no reduction in foraging effort for three whales exposed to incidental, unidentified 4.7-5.1 kHz sonar signals received at lower levels (SPL = 89-133 dB re 1 µPa). These results demonstrate that similar to predation risk, exposure to sonar can affect functional behaviors, and indicate that increased perception of risk with higher source level or lower frequency may modulate how sperm whales respond to anthropogenic sound.

  4. High-resolution seismic and side scan sonar imaging of active structures and Quaternary channels on the shallow shelf of Otago, southeastern New Zealand

    NASA Astrophysics Data System (ADS)

    Gorman, A. R.; Bruce, C.; Preskett, S. A.; Norris, R.; Choveaux, R.; Flemish, H.; Green, C.

    2011-12-01

    The shallow and narrow continental shelf off the coast of Otago has unique geological characteristics due to the juxtaposition of active coast-parallel contractional faults related to the nearby Pacific-Australian plate boundary and late-Miocene shield volcanism that affects the structural and sedimentological regimes of the region. For example, the offshore extent of the active Akatore Fault, a NE-SW trending reverse fault that runs along the coast SW of Dunedin, is poorly constrained to the northeast where is intersects the Dunedin Volcanic Complex. This fault is possibly associated with several other offshore coast-parallel faults based on shallow controlled-source seismic data. Historical earthquakes, including those of 1974 and 1989, are attributed these faults. The Dunedin Volcanic Complex also has impacted Quaternary erosional and sedimentation patterns on the shelf as a result of topographical features that affect drainage and sediment transport patterns. Single-channel electro-acoustic boomer seismic reflection data and side scan sonar profiles have been collected along a ~35-km-long section of the shallow shelf SW of Dunedin over the last three years. The majority of lines were collected along NW-SE azimuths (perpendicular to the coast), running from just outside the surf zone (<10 m water depth) to a maximum of 28 km offshore (~75 m water depth). Survey lines were ~250 m apart near shore and up to 5 km apart offshore. Boomer subsurface penetration is limited, primarily by the presence of multiple reflections. However, primary reflections were recorded from sub-seafloor depths of up to 100 m. Several significant structures have been imaged within the survey area, principally the Akatore and Green Island Faults. The Akatore Fault is imaged very near shore in the southern portion of the survey, and a minimum post-Miocene displacement of 55 m was calculated. Offset on the Green Island Fault, a high-angle reverse fault, was relatively well constrained to ~200

  5. Sonar equations for planetary exploration.

    PubMed

    Ainslie, Michael A; Leighton, Timothy G

    2016-08-01

    The set of formulations commonly known as "the sonar equations" have for many decades been used to quantify the performance of sonar systems in terms of their ability to detect and localize objects submerged in seawater. The efficacy of the sonar equations, with individual terms evaluated in decibels, is well established in Earth's oceans. The sonar equations have been used in the past for missions to other planets and moons in the solar system, for which they are shown to be less suitable. While it would be preferable to undertake high-fidelity acoustical calculations to support planning, execution, and interpretation of acoustic data from planetary probes, to avoid possible errors for planned missions to such extraterrestrial bodies in future, doing so requires awareness of the pitfalls pointed out in this paper. There is a need to reexamine the assumptions, practices, and calibrations that work well for Earth to ensure that the sonar equations can be accurately applied in combination with the decibel to extraterrestrial scenarios. Examples are given for icy oceans such as exist on Europa and Ganymede, Titan's hydrocarbon lakes, and for the gaseous atmospheres of (for example) Jupiter and Venus.

  6. Beaked Whales Respond to Simulated and Actual Navy Sonar

    DTIC Science & Technology

    2011-03-14

    fundamental frequency of MFA sonars, and it is possible that these harmonics may be involved in the response. Another hypothesis for why these tonal ... tonal components in the 3– 4 kHz band, a pseudorandom noise signal (PRN) with overall bandwidth and timing similar to MFA, and killer whale (ORCA...sufficient signal to noise ratio to use as stimuli. Harbor seals react to the calls of strange killer whales as a predator [33], and this is typical

  7. Stability augmentation and mosaic method of forward-scan sonar images

    NASA Astrophysics Data System (ADS)

    Xie, Shaorong; Luo, Jun; Chen, Jinbo; Xu, Yuanyu

    2012-06-01

    In recent years, forward-scan sonar is widely applied to the underwater inspection, which is not subject to the influence of light and turbidity. For expanding the monitoring scope, the image sonar is generally mounted on the pan-tilt platform of a ROV (Remotely Operated Vehicle) or survey boat. However, there are still some problems such as: 1) The field-of-view is narrow, i.e. the horizontal view angle of DIDSON (Dual-frequency identification sonar) is 29° 2) The dynamic change of a ROV or survey boat by the water disturbances will cause the target to escape from the sonar image easily; 3) The image sonar is fixed on the pan-tilt platform, and its position and posture are unceasingly changed. As a result of these problems, the obtained images may be distorted and not on the same plane. To solve the above problems, stability augmentation of pan-tilt platform based on the principle of bionic eye movements and a mosaic method of sonar images are presented. According to the principle of the vestibule-ocular reflex, an active compensation control system of the mechanical pan-tilt platform is developed. It can compensate the sonar image instability resulting from attitude variation of a ROV or survey boat during operation. Applying multi-sensor fusion technology can rectify the sonar images with different position and posture to be on a single geodetic coordinate frame for image matching. Finally, sonar images can be mosaic. A stable large-scale sonar image can be obtained. The experimental results validate that the presented method is valid.

  8. Wreck finding and classifying with a sonar filter

    NASA Astrophysics Data System (ADS)

    Agehed, Kenneth I.; Padgett, Mary Lou; Becanovic, Vlatko; Bornich, C.; Eide, Age J.; Engman, Per; Globoden, O.; Lindblad, Thomas; Lodgberg, K.; Waldemark, Karina E.

    1999-03-01

    Sonar detection and classification of sunken wrecks and other objects is of keen interest to many. This paper describes the use of neural networks (NN) for locating, classifying and determining the alignment of objects on a lakebed in Sweden. A complex program for data preprocessing and visualization was developed. Part of this program, The Sonar Viewer, facilitates training and testing of the NN using (1) the MATLAB Neural Networks Toolbox for multilayer perceptrons with backpropagation (BP) and (2) the neural network O-Algorithm (OA) developed by Age Eide and Thomas Lindblad. Comparison of the performance of the two neural networks approaches indicates that, for this data BP generalizes better than OA, but use of OA eliminates the need for training on non-target (lake bed) images. The OA algorithm does not work well with the smaller ships. Increasing the resolution to counteract this problem would slow down processing and require interpolation to suggest data values between the actual sonar measurements. In general, good results were obtained for recognizing large wrecks and determining their alignment. The programs developed a useful tool for further study of sonar signals in many environments. Recent developments in pulse coupled neural networks techniques provide an opportunity to extend the use in real-world applications where experimental data is difficult, expensive or time consuming to obtain.

  9. Hulu Sungai Perak Bed Sediment Mapping Using Underwater Acoustic Sonar

    NASA Astrophysics Data System (ADS)

    Arriafdi, N.; Zainon, O.; Din, U.; Rasid, A. W.; Mat Amin, Z.; Othman, R.; Mardi, A. S.; Mahmud, R.; Sulaiman, N.

    2016-09-01

    Development in acoustic survey techniques in particular side scan sonar have revolutionized the way we are able to image, map and understand the riverbed environment. It is now cost effective to image large areas of the riverbed using these techniques and the backscatter image created from surveys provides base line data from which thematic maps of the riverbed environment including maps of morphological geology, can be derived when interpreted in conjunction with in situ sampling data. This article focuses on investigation characteristics of sediments and correlation of side scan backscatter image with signal strength. The interpretation of acoustic backscatter rely on experienced interpretation by eye of grey scale images produced from the data. A 990F Starfish Side Scan Sonar was used to collect and develop a series of sonar images along 6 km of Hulu Sungai Perak. Background sediments could be delineated accurately and the image textures could be linked to the actual river floor appearance through grab sampling. A major difference was found in the acoustic returns from the two research area studies: the upstream area shows much rougher textures. This is due to an actual differences in riverbed roughness, caused by a difference in bottom currents and sediment dynamics in the two areas. The highest backscatter correlates with coarsest and roughness sediment. Result suggest that image based backscatter classification shows considerable promise for interpretation of side scan sonar data for the production of geological maps.

  10. Marine Mammals and Active Sonar

    DTIC Science & Technology

    2005-10-01

    small effort to look at noise impacts on Beluga whales also serves to build expertise and an understanding of the general complexities. A new...Thomas, and R. A. Kastelein. 1988. Low-frequency underwater hearing sensitivity in belugas , Delphinapterus leucas. Journal of the Acoustical Society of...C. and Farmer, D. M. 2000. Zones of impact around icebreakers affecting beluga whales in the Beaufort Sea. Journal of the Acoustical Society of

  11. Biomarkers to Assess Possible Biological Effects on Reproductive Potential, Immune Function, and Energetic Fitness of Bottlenose Dolphins Exposed to Sounds Consistent with Naval Sonars

    DTIC Science & Technology

    2012-09-30

    Reproductive Potential, Immune Function, and Energetic Fitness of Bottlenose Dolphins Exposed to Sounds Consistent with Naval Sonars Dana L. Wetzel...biomarkers to examine whether significant sublethal responses to sonar-type sounds occur in bottlenose dolphins exposed to such sounds. The...investigate samples collected from trained dolphins before exposure to simulated mid-frequency sonar signals, immediately after exposure, and one week post

  12. A Study to Interpret the Biological Significance of Behavior Associated with 3S Experimental Sonar Exposures

    DTIC Science & Technology

    2015-09-30

    playback of killer whale sounds across the 3S species; and 3.) quantification of the possible impacts of sonar exposure on energy expenditure by linking respiration behavior and underwater activity recorded by Dtags.

  13. Sonar sound groups and increased terminal buzz duration reflect task complexity in hunting bats.

    PubMed

    Hulgard, Katrine; Ratcliffe, John M

    2016-02-09

    More difficult tasks are generally regarded as such because they demand greater attention. Echolocators provide rare insight into this relationship because biosonar signals can be monitored. Here we show that bats produce longer terminal buzzes and more sonar sound groups during their approach to prey under presumably more difficult conditions. Specifically, we found Daubenton's bats, Myotis daubentonii, produced longer buzzes when aerial-hawking versus water-trawling prey, but that bats taking revolving air- and water-borne prey produced more sonar sound groups than did the bats when taking stationary prey. Buzz duration and sonar sound groups have been suggested to be independent means by which bats attend to would-be targets and other objects of interest. We suggest that for attacking bats both should be considered as indicators of task difficulty and that the buzz is, essentially, an extended sonar sound group.

  14. Sonar sound groups and increased terminal buzz duration reflect task complexity in hunting bats

    PubMed Central

    Hulgard, Katrine; Ratcliffe, John M.

    2016-01-01

    More difficult tasks are generally regarded as such because they demand greater attention. Echolocators provide rare insight into this relationship because biosonar signals can be monitored. Here we show that bats produce longer terminal buzzes and more sonar sound groups during their approach to prey under presumably more difficult conditions. Specifically, we found Daubenton’s bats, Myotis daubentonii, produced longer buzzes when aerial-hawking versus water-trawling prey, but that bats taking revolving air- and water-borne prey produced more sonar sound groups than did the bats when taking stationary prey. Buzz duration and sonar sound groups have been suggested to be independent means by which bats attend to would-be targets and other objects of interest. We suggest that for attacking bats both should be considered as indicators of task difficulty and that the buzz is, essentially, an extended sonar sound group. PMID:26857019

  15. Heparin activates Wnt signaling for neuronal morphogenesis.

    PubMed

    Colombres, Marcela; Henríquez, Juan Pablo; Reig, Germán F; Scheu, Jessica; Calderón, Rosario; Alvarez, Alejandra; Brandan, Enrique; Inestrosa, Nibaldo C

    2008-09-01

    Wnt factors are secreted ligands that affect different aspects of the nervous system behavior like neurodevelopment, synaptogenesis and neurodegeneration. In different model systems, Wnt signaling has been demonstrated to be regulated by heparan sulfate proteoglycans (HSPGs). Whether HSPGs modulate Wnt signaling in the context of neuronal behavior is currently unknown. Here we demonstrate that activation of Wnt signaling with the endogenous ligand Wnt-7a results in an increased of neurite outgrowth in the neuroblastoma N2a cell line. Interestingly, heparin induces glycogen synthase kinase-3beta (GSK-3beta) inhibition, beta-catenin stabilization and morphological differentiation in both N2a cells and in rat primary hippocampal neuronal cultures. We also show that heparin modulates Wnt-3a-induced stabilization of beta-catenin. Several extracellular matrix and membrane-attached HSPGs were found to be expressed in both in vitro neuronal models. Changes in the expression of specific HSPGs were observed upon differentiation of N2a cells. Taken together, our findings suggest that HSPGs may modulate canonical Wnt signaling for neuronal morphogenesis.

  16. Array signal processing

    SciTech Connect

    Haykin, S.; Justice, J.H.; Owsley, N.L.; Yen, J.L.; Kak, A.C.

    1985-01-01

    This is the first book to be devoted completely to array signal processing, a subject that has become increasingly important in recent years. The book consists of six chapters. Chapter 1, which is introductory, reviews some basic concepts in wave propagation. The remaining five chapters deal with the theory and applications of array signal processing in (a) exploration seismology, (b) passive sonar, (c) radar, (d) radio astronomy, and (e) tomographic imaging. The various chapters of the book are self-contained. The book is written by a team of five active researchers, who are specialists in the individual fields covered by the pertinent chapters.

  17. Neural networks for improved target differentiation and localization with sonar.

    PubMed

    Ayrulu, B; Barshan, B

    2001-04-01

    This study investigates the processing of sonar signals using neural networks for robust differentiation of commonly encountered features in indoor robot environments. Differentiation of such features is of interest for intelligent systems in a variety of applications. Different representations of amplitude and time-of-flight measurement patterns acquired from a real sonar system are processed. In most cases, best results are obtained with the low-frequency component of the discrete wavelet transform of these patterns. Modular and non-modular neural network structures trained with the back-propagation and generating-shrinking algorithms are used to incorporate learning in the identification of parameter relations for target primitives. Networks trained with the generating-shrinking algorithm demonstrate better generalization and interpolation capability and faster convergence rate. Neural networks can differentiate more targets employing only a single sensor node, with a higher correct differentiation percentage (99%) than achieved with previously reported methods (61-90%) employing multiple sensor nodes. A sensor node is a pair of transducers with fixed separation, that can rotate and scan the target to collect data. Had the number of sensing nodes been reduced in the other methods, their performance would have been even worse. The success of the neural network approach shows that the sonar signals do contain sufficient information to differentiate all target types, but the previously reported methods are unable to resolve this identifying information. This work can find application in areas where recognition of patterns hidden in sonar signals is required. Some examples are system control based on acoustic signal detection and identification, map building, navigation, obstacle avoidance, and target-tracking applications for mobile robots and other intelligent systems.

  18. Sonar Test and Test Instrumentation Support.

    DTIC Science & Technology

    1976-11-10

    6487 < rM SEL ECTE CO, BU 9 1 Approved for public release;distribution unlimited. 611 095 A DNAR IA ST WI EST INSTRUMENTATIONJUPPORT.J ) Quaterly ...INSTRUMENTATION TEST AND EVALUATION 17 A. Introduction 17 B. Operational Testing of the AN/WQM-7 Sonar Test Set 17 C. AN/SQM-( ) Feasibility Study 19 VII. STUDY ...AN/WQM-5 Sonar Test Set Field Support IV. Special Purpose Passive Sonar Systems Support V. Sonar Instrumentation Test and Evaluation VI. Study of

  19. Place recognition using batlike sonar.

    PubMed

    Vanderelst, Dieter; Steckel, Jan; Boen, Andre; Peremans, Herbert; Holderied, Marc W

    2016-08-02

    Echolocating bats have excellent spatial memory and are able to navigate to salient locations using bio-sonar. Navigating and route-following require animals to recognize places. Currently, it is mostly unknown how bats recognize places using echolocation. In this paper, we propose template based place recognition might underlie sonar-based navigation in bats. Under this hypothesis, bats recognize places by remembering their echo signature - rather than their 3D layout. Using a large body of ensonification data collected in three different habitats, we test the viability of this hypothesis assessing two critical properties of the proposed echo signatures: (1) they can be uniquely classified and (2) they vary continuously across space. Based on the results presented, we conclude that the proposed echo signatures satisfy both criteria. We discuss how these two properties of the echo signatures can support navigation and building a cognitive map.

  20. Echo Statistics of Aggregations of Scatterers in a Random Waveguide: Application to Biologic Sonar Clutter

    DTIC Science & Technology

    2012-09-01

    matched-filtered data, while lower panels show matched-filtered, split - window-normalized results. An echo that is likely from a fish school is...and non-target scatterers within the water column, often limits active sonar system performance. Fish can constitute a significant portion of sonar...by fish with resonant gas-filled swimbladders can dominate over bottom or surface reverberation. This study examines the contributions of various

  1. Improving the Information Content of Sonar Signals

    DTIC Science & Technology

    1997-09-30

    and down-Doppler shifts from the same dissipating wake ! IMPACT/APPLICATION . Synthetic aperture imaging was reformulated as a problem in parametric ... estimation . That this technique is superior to other techniques is manifest, because the class of parameter models considered contains the models

  2. Sleep Loss Activates Cellular Inflammatory Signaling

    PubMed Central

    Irwin, Michael R.; Wang, Minge; Ribeiro, Denise; Cho, Hyong Jin; Olmstead, Richard; Breen, Elizabeth Crabb; Martinez-Maza, Otoniel; Cole, Steve

    2008-01-01

    Background Accumulating evidence suggests that sleep disturbance is associated with inflammation and related disorders including cardiovascular disease, arthritis, and diabetes mellitus. This study was undertaken to test the effects of sleep loss on activation of nuclear factor (NF) -κB, a transcription factor that serves a critical role in the inflammatory signaling cascade. Methods In 14 healthy adults (7 females; 7 males), peripheral blood mononuclear cell NF-κB was repeatedly assessed, along with enumeration of lymphocyte subpopulations, in the morning after baseline sleep, partial sleep deprivation (awake from 23:00 h to 03:00 h), and recovery sleep. Results In the morning after a night of sleep loss, mononuclear cell NF-κB activation was significantly greater compared with morning levels following uninterrupted baseline or recovery sleep, in which the response was found in females but not in males. Conclusions These results identify NF-κB activation as a molecular pathway by which sleep disturbance may influence leukocyte inflammatory gene expression and the risk of inflammation-related disease. PMID:18561896

  3. Heat dissipation guides activation in signaling proteins

    PubMed Central

    Weber, Jeffrey K.; Shukla, Diwakar; Pande, Vijay S.

    2015-01-01

    Life is fundamentally a nonequilibrium phenomenon. At the expense of dissipated energy, living things perform irreversible processes that allow them to propagate and reproduce. Within cells, evolution has designed nanoscale machines to do meaningful work with energy harnessed from a continuous flux of heat and particles. As dictated by the Second Law of Thermodynamics and its fluctuation theorem corollaries, irreversibility in nonequilibrium processes can be quantified in terms of how much entropy such dynamics produce. In this work, we seek to address a fundamental question linking biology and nonequilibrium physics: can the evolved dissipative pathways that facilitate biomolecular function be identified by their extent of entropy production in general relaxation processes? We here synthesize massive molecular dynamics simulations, Markov state models (MSMs), and nonequilibrium statistical mechanical theory to probe dissipation in two key classes of signaling proteins: kinases and G-protein–coupled receptors (GPCRs). Applying machinery from large deviation theory, we use MSMs constructed from protein simulations to generate dynamics conforming to positive levels of entropy production. We note the emergence of an array of peaks in the dynamical response (transient analogs of phase transitions) that draw the proteins between distinct levels of dissipation, and we see that the binding of ATP and agonist molecules modifies the observed dissipative landscapes. Overall, we find that dissipation is tightly coupled to activation in these signaling systems: dominant entropy-producing trajectories become localized near important barriers along known biological activation pathways. We go on to classify an array of equilibrium and nonequilibrium molecular switches that harmonize to promote functional dynamics. PMID:26240354

  4. Active voltammetric microsensors with neural signal processing.

    SciTech Connect

    Vogt, M. C.

    1998-12-11

    Many industrial and environmental processes, including bioremediation, would benefit from the feedback and control information provided by a local multi-analyte chemical sensor. For most processes, such a sensor would need to be rugged enough to be placed in situ for long-term remote monitoring, and inexpensive enough to be fielded in useful numbers. The multi-analyte capability is difficult to obtain from common passive sensors, but can be provided by an active device that produces a spectrum-type response. Such new active gas microsensor technology has been developed at Argonne National Laboratory. The technology couples an electrocatalytic ceramic-metallic (cermet) microsensor with a voltammetric measurement technique and advanced neural signal processing. It has been demonstrated to be flexible, rugged, and very economical to produce and deploy. Both narrow interest detectors and wide spectrum instruments have been developed around this technology. Much of this technology's strength lies in the active measurement technique employed. The technique involves applying voltammetry to a miniature electrocatalytic cell to produce unique chemical ''signatures'' from the analytes. These signatures are processed with neural pattern recognition algorithms to identify and quantify the components in the analyte. The neural signal processing allows for innovative sampling and analysis strategies to be employed with the microsensor. In most situations, the whole response signature from the voltammogram can be used to identify, classify, and quantify an analyte, without dissecting it into component parts. This allows an instrument to be calibrated once for a specific gas or mixture of gases by simple exposure to a multi-component standard rather than by a series of individual gases. The sampled unknown analytes can vary in composition or in concentration, the calibration, sensing, and processing methods of these active voltammetric microsensors can detect, recognize, and

  5. 50 CFR 218.100 - Specified activity and specified geographical area.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... active sonar (MFAS) and high frequency active sonar (HFAS) sources, or similar sources, for Navy training...-53 (hull-mounted active sonar)—up to 10865 hours over the course of 5 years (an average of 2173 hours per year); (ii) AN/SQS-56 (hull-mounted active sonar)-up to 705 hours over the course of 5 years...

  6. 50 CFR 218.100 - Specified activity and specified geographical area.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... active sonar (MFAS) and high frequency active sonar (HFAS) sources, or similar sources, for Navy training...-53 (hull-mounted active sonar)—up to 10865 hours over the course of 5 years (an average of 2173 hours per year); (ii) AN/SQS-56 (hull-mounted active sonar)-up to 705 hours over the course of 5 years...

  7. 50 CFR 216.270 - Specified activity and specified geographical region.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... the following mid-frequency active sonar (MFAS) and high frequency active sonar (HFAS) sources, or...) (estimated amounts below): (i) AN/SQS-53 (hull-mounted active sonar)—up to 9885 hours over the course of 5 years (an average of 1977 hours per year) (ii) AN/SQS-56 (hull-mounted active sonar)—up to 2470...

  8. Computers improves sonar seabed maps

    SciTech Connect

    Not Available

    1984-05-01

    A software package for computer aided mapping of sonar (CAMOS) has been developed in Norway. It has automatic mosaic presentation, which produces fully scale-rectified side scan sonograms automatically plotted on geographical and UTM map grids. The program is the first of its kind in the world. The maps produced by this method are more accurate and detailed than those produced by conventional methods. The main applications of CAMOS are: seafloor mapping; pipeline route surveys; pipeline inspection surveys; platform site surveys; geological mapping and geotechnical investigations. With the aerial-photograph quality of the CAMOS maps, a more accurate and visual representation of the seabed is achieved.

  9. Qualitative and quantitative processing of side-scan sonar data

    SciTech Connect

    Dwan, F.S.; Anderson, A.L.; Hilde, T.W.C. )

    1990-06-01

    Modern side-scan sonar systems allow vast areas of seafloor to be rapidly imaged and quantitatively mapped in detail. The application of remote sensing image processing techniques can be used to correct for various distortions inherent in raw sonography. Corrections are possible for water column, slant-range, aspect ratio, speckle and striping noise, multiple returns, power drop-off, and for georeferencing. The final products reveal seafloor features and patterns that are geometrically correct, georeferenced, and have improved signal/noise ratio. These products can be merged with other georeferenced data bases for further database management and information extraction. In order to compare data collected by different systems from a common area and to ground truth measurements and geoacoustic models, quantitative correction must be made for calibrated sonar system and bathymetry effects. Such data inversion must account for system source level, beam pattern, time-varying gain, processing gain, transmission loss, absorption, insonified area, and grazing angle effects. Seafloor classification can then be performed on the calculated back-scattering strength using Lambert's Law and regression analysis. Examples are given using both approaches: image analysis and inversion of data based on the sonar equation.

  10. Estimation and simulation of multi-beam sonar noise.

    PubMed

    Holmin, Arne Johannes; Korneliussen, Rolf J; Tjøstheim, Dag

    2016-02-01

    Methods for the estimation and modeling of noise present in multi-beam sonar data, including the magnitude, probability distribution, and spatial correlation of the noise, are developed. The methods consider individual acoustic samples and facilitate compensation of highly localized noise as well as subtraction of noise estimates averaged over time. The modeled noise is included in an existing multi-beam sonar simulation model [Holmin, Handegard, Korneliussen, and Tjøstheim, J. Acoust. Soc. Am. 132, 3720-3734 (2012)], resulting in an improved model that can be used to strengthen interpretation of data collected in situ at any signal to noise ratio. Two experiments, from the former study in which multi-beam sonar data of herring schools were simulated, are repeated with inclusion of noise. These experiments demonstrate (1) the potentially large effect of changes in fish orientation on the backscatter from a school, and (2) the estimation of behavioral characteristics such as the polarization and packing density of fish schools. The latter is achieved by comparing real data with simulated data for different polarizations and packing densities.

  11. Application of acoustic reflection tomography to sonar imaging.

    PubMed

    Ferguson, Brian G; Wyber, Ron J

    2005-05-01

    Computer-aided tomography is a technique for providing a two-dimensional cross-sectional view of a three-dimensional object through the digital processing of many one-dimensional views (or projections) taken at different look directions. In acoustic reflection tomography, insonifying the object and then recording the backscattered signal provides the projection information for a given look direction (or aspect angle). Processing the projection information for all possible aspect angles enables an image to be reconstructed that represents the two-dimensional spatial distribution of the object's acoustic reflectivity function when projected on the imaging plane. The shape of an idealized object, which is an elliptical cylinder, is reconstructed by applying standard backprojection, Radon transform inversion (using both convolution and filtered backprojections), and direct Fourier inversion to simulated projection data. The relative merits of the various reconstruction algorithms are assessed and the resulting shape estimates compared. For bandpass sonar data, however, the wave number components of the acoustic reflectivity function that are outside the passband are absent. This leads to the consideration of image reconstruction for bandpass data. Tomographic image reconstruction is applied to real data collected with an ultra-wideband sonar transducer to form high-resolution acoustic images of various underwater objects when the sonar and object are widely separated.

  12. 50 CFR 218.110 - Specified activity and specified geographical area.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... sonar (MFAS) and high frequency active sonar (HFAS) sources, or similar sources, for Navy training...-53 (hull-mounted active sonar)—up to 215 hours over the course of 5 years (an average of 43 hours per year); (ii) AN/SQS-56 (hull-mounted active sonar)—up to 325 hours over the course of 5 years...

  13. 50 CFR 218.110 - Specified activity and specified geographical area.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... sonar (MFAS) and high frequency active sonar (HFAS) sources, or similar sources, for Navy training...-53 (hull-mounted active sonar)—up to 215 hours over the course of 5 years (an average of 43 hours per year); (ii) AN/SQS-56 (hull-mounted active sonar)—up to 325 hours over the course of 5 years...

  14. Place recognition using batlike sonar

    PubMed Central

    Vanderelst, Dieter; Steckel, Jan; Boen, Andre; Peremans, Herbert; Holderied, Marc W

    2016-01-01

    Echolocating bats have excellent spatial memory and are able to navigate to salient locations using bio-sonar. Navigating and route-following require animals to recognize places. Currently, it is mostly unknown how bats recognize places using echolocation. In this paper, we propose template based place recognition might underlie sonar-based navigation in bats. Under this hypothesis, bats recognize places by remembering their echo signature - rather than their 3D layout. Using a large body of ensonification data collected in three different habitats, we test the viability of this hypothesis assessing two critical properties of the proposed echo signatures: (1) they can be uniquely classified and (2) they vary continuously across space. Based on the results presented, we conclude that the proposed echo signatures satisfy both criteria. We discuss how these two properties of the echo signatures can support navigation and building a cognitive map. DOI: http://dx.doi.org/10.7554/eLife.14188.001 PMID:27481189

  15. Using vertical Sidescan Sonar as a tool for seagrass cartography

    NASA Astrophysics Data System (ADS)

    Sánchez-Carnero, N.; Rodríguez-Pérez, D.; Couñago, E.; Aceña, S.; Freire, J.

    2012-12-01

    An acoustic method, a vertically oriented Sidescan Sonar (SSSv), is used to detect and map Posidonia oceanica meadows in the bay of Agua Amarga (SE of the Mediterranean coast of Spain). Sidescan sonar, among other active hydroacoustic techniques, has shown its ability to detect, map and monitor seagrass based on its acoustic backscatter; however, some limitations linked to its power based approach have been reported in the literature. Our method is based on the SSSv measurement of canopy height distribution, making the most use of the SSSv acoustic data and using existing algorithms as statistical mapping methods. The results show a spatially coherent and statistically consistent classification. The comparison with groundtruthing is difficult due to the steep variations in the seafloor cover found in the area of interest, nevertheless the validation is successful (proving low-order discrimination) in a zone with a large range of depth variations (0-25 m).

  16. Signal Destruction Tunes the Zone of Activation in Spatially Distributed Signaling Networks.

    PubMed

    Silva, Kalinga Pavan; Chellamuthu, Prithiviraj; Boedicker, James Q

    2017-03-14

    Diverse microbial communities coordinate group behaviors through signal exchange, such as the exchange of acyl-homoserine lactones (AHLs) by Gram-negative bacteria. Cellular communication is prone to interference by neighboring microbes. One mechanism of interference is signal destruction through the production of an enzyme that cleaves the signaling molecule. Here we examine the ability of one such interference enzyme, AiiA, to modulate signal propagation in a spatially distributed system of bacteria. We have developed an experimental assay to measure signal transduction and implement a theoretical model of signaling dynamics to predict how the system responds to interference. We show that titration of an interfering strain into a signaling network tunes the spatial range of activation over the centimeter length scale, quantifying the robustness of the signaling network to signal destruction and demonstrating the ability to program systems-level responses of spatially heterogeneous cellular networks.

  17. Detecting the presence-absence of bluefin tuna by automated analysis of medium-range sonars on fishing vessels

    PubMed Central

    Uranga, Jon; Arrizabalaga, Haritz; Boyra, Guillermo; Hernandez, Maria Carmen; Goñi, Nicolas; Arregui, Igor; Fernandes, Jose A.; Yurramendi, Yosu; Santiago, Josu

    2017-01-01

    This study presents a methodology for the automated analysis of commercial medium-range sonar signals for detecting presence/absence of bluefin tuna (Tunnus thynnus) in the Bay of Biscay. The approach uses image processing techniques to analyze sonar screenshots. For each sonar image we extracted measurable regions and analyzed their characteristics. Scientific data was used to classify each region into a class (“tuna” or “no-tuna”) and build a dataset to train and evaluate classification models by using supervised learning. The methodology performed well when validated with commercial sonar screenshots, and has the potential to automatically analyze high volumes of data at a low cost. This represents a first milestone towards the development of acoustic, fishery-independent indices of abundance for bluefin tuna in the Bay of Biscay. Future research lines and additional alternatives to inform stock assessments are also discussed. PMID:28152032

  18. Detecting the presence-absence of bluefin tuna by automated analysis of medium-range sonars on fishing vessels.

    PubMed

    Uranga, Jon; Arrizabalaga, Haritz; Boyra, Guillermo; Hernandez, Maria Carmen; Goñi, Nicolas; Arregui, Igor; Fernandes, Jose A; Yurramendi, Yosu; Santiago, Josu

    2017-01-01

    This study presents a methodology for the automated analysis of commercial medium-range sonar signals for detecting presence/absence of bluefin tuna (Tunnus thynnus) in the Bay of Biscay. The approach uses image processing techniques to analyze sonar screenshots. For each sonar image we extracted measurable regions and analyzed their characteristics. Scientific data was used to classify each region into a class ("tuna" or "no-tuna") and build a dataset to train and evaluate classification models by using supervised learning. The methodology performed well when validated with commercial sonar screenshots, and has the potential to automatically analyze high volumes of data at a low cost. This represents a first milestone towards the development of acoustic, fishery-independent indices of abundance for bluefin tuna in the Bay of Biscay. Future research lines and additional alternatives to inform stock assessments are also discussed.

  19. Kinase active Misshapen regulates Notch signaling in Drosophila melanogaster.

    PubMed

    Mishra, Abhinava K; Sachan, Nalani; Mutsuddi, Mousumi; Mukherjee, Ashim

    2015-11-15

    Notch signaling pathway represents a principal cellular communication system that plays a pivotal role during development of metazoans. Drosophila misshapen (msn) encodes a protein kinase, which is related to the budding yeast Ste20p (sterile 20 protein) kinase. In a genetic screen, using candidate gene approach to identify novel kinases involved in Notch signaling, we identified msn as a novel regulator of Notch signaling. Data presented here suggest that overexpression of kinase active form of Msn exhibits phenotypes similar to Notch loss-of-function condition and msn genetically interacts with components of Notch signaling pathway. Kinase active form of Msn associates with Notch receptor and regulate its signaling activity. We further show that kinase active Misshapen leads to accumulation of membrane-tethered form of Notch. Moreover, activated Msn also depletes Armadillo and DE-Cadherin from adherens junctions. Thus, this study provides a yet unknown mode of regulation of Notch signaling by Misshapen.

  20. Evolution: Fossil Ears and Underwater Sonar.

    PubMed

    Lambert, Olivier

    2016-08-22

    A key innovation in the history of whales was the evolution of a sonar system together with high-frequency hearing. Fossils of an archaic toothed whale's inner ear bones provide clues for a stepwise emergence of underwater echolocation ability.

  1. Extraction of small boat harmonic signatures from passive sonar.

    PubMed

    Ogden, George L; Zurk, Lisa M; Jones, Mark E; Peterson, Mary E

    2011-06-01

    This paper investigates the extraction of acoustic signatures from small boats using a passive sonar system. Noise radiated from a small boats consists of broadband noise and harmonically related tones that correspond to engine and propeller specifications. A signal processing method to automatically extract the harmonic structure of noise radiated from small boats is developed. The Harmonic Extraction and Analysis Tool (HEAT) estimates the instantaneous fundamental frequency of the harmonic tones, refines the fundamental frequency estimate using a Kalman filter, and automatically extracts the amplitudes of the harmonic tonals to generate a harmonic signature for the boat. Results are presented that show the HEAT algorithms ability to extract these signatures.

  2. Remote characterizing diffuse hydrothermal flows using multi-beam sonar

    NASA Astrophysics Data System (ADS)

    Ivakin, A. N.; Jackson, D. R.; Bemis, K. G.; Xu, G.

    2015-12-01

    Multi-beam sonars are normally used for bottom bathymetry and backscatter intensity measurements, which provide a base for remotely characterizing the seabed. If not only sonar echo intensity (squared magnitude of acoustic pressure) but also the cross-correlation between successive echoes is measured, then temporal changes in sound speed in the near-bottom environment can be determined. This, in turn, allows estimation of the change of environmental parameters, e.g. temperature variations, as there is a simple linear relationship between sound speed and temperature changes. Stochastic modeling shows that the dependence of the echo decorrelation on the lag time has a relationship with the statistics of temperature variations above the seabed that determine their spatial and temporal scales, power spectra, and structure functions. This approach has been applied to quantify the bottom diffuse hydrothermal flow activity at the Main Endeavour Field on the Juan de Fuca Ridge using the Cabled Observatory Vent Imaging Sonar (COVIS) connected to the Ocean Network Canada's NEPTUNE observatory. In contrast to our previous work, which was focused on spatial imaging of acoustic decorrelation at fixed lag, here the lag dependence of the acoustic structure function is measured and analyzed. This allows extraction of additional parameters of temperature fluctuation statistics. A potential to map diffuse flow using a ROV/HOV is discussed.

  3. Ceteacean Social Behavioral Response to Sonar

    DTIC Science & Technology

    2014-09-30

    experimental sonar exposure in SOCAL-BRS (Risso’s dolphin )  Data-collection: Baseline social behavior - SOCAL-BRS projects (Risso’s dolphin ...playbacks using visual observation techniques 3 - Species evaluated: long-beaked common dolphin , bottlenose dolphin , killer whale - 2014: Design...data processing and analysis for Risso’s dolphin sonar response (SOCAL-BRS, Azores-Baseline) - Cross-study cooperation in data processing and analysis

  4. Reported Modality Preferences of Sonar Operators

    DTIC Science & Technology

    1991-02-01

    indicated a preference for the visual modality, which was similar in proportion for both STS and STG groups. On questions pertinent to sonar operation...most operators indicated a visual preference. However, on two of these items, proportionally more STS than STG operators showed an auditory...preference. Interestingly, 99% of all the subjects reported that present sonar systems are biased toward visual information. Yet, this survey showed that only

  5. AUV-12 Sonar Integration and Evaluation

    DTIC Science & Technology

    2010-02-26

    extension has been granted. Expenditures Authorized Title Labor ODC Com- mitted Total Funding Balance Start End AUV Sonar - CLIN-1 $214,144...36,520 $0 $250,664 $357,473 $106,809 01/29/09 01/29/10 AUV Sonar - CLIN-2 $869 $0 $0 $869 $74,385 $73,516 11/23/09 07/22/10 Total $215,012 $36,520 $0

  6. Human ECG signal parameters estimation during controlled physical activity

    NASA Astrophysics Data System (ADS)

    Maciejewski, Marcin; Surtel, Wojciech; Dzida, Grzegorz

    2015-09-01

    ECG signal parameters are commonly used indicators of human health condition. In most cases the patient should remain stationary during the examination to decrease the influence of muscle artifacts. During physical activity, the noise level increases significantly. The ECG signals were acquired during controlled physical activity on a stationary bicycle and during rest. Afterwards, the signals were processed using a method based on Pan-Tompkins algorithms to estimate their parameters and to test the method.

  7. Shallow water imaging sonar system for environmental surveying. Final report

    SciTech Connect

    1998-05-01

    The scope of this research is to develop a shallow water sonar system designed to detect and map the location of objects such as hazardous wastes or discarded ordnance in coastal waters. The system will use high frequency wide-bandwidth imaging sonar, mounted on a moving platform towed behind a boat, to detect and identify objects on the sea bottom. Resolved images can be obtained even if the targets are buried in an overlayer of silt. The specific technical objective of this research was to develop and test a prototype system that is capable of (1) scan at high speeds (up to 10m/s), even in shallow water (depth to ten meters), without motion blurring or loss of resolution; (2) produce images of the bottom structure that are detailed enough for unambiguous detection of objects as small as 15cm, even if they are buried up to 30cm deep in silt or sand. The critical technology involved uses an linear FM (LFM) or similar complex waveform, which has a high bandwidth for good range resolution, with a long pulse length for similar Dopper resolution. The lone duration signal deposits more energy on target than a narrower pulse, which increases the signal-to-noise ratio and signal-to-clutter ratio. This in turn allows the use of cheap, lightweight, low power, piezoelectric transducers at the 30--500 kHz range.

  8. Activation of DNA damage response signaling by condensed chromatin.

    PubMed

    Burgess, Rebecca C; Burman, Bharat; Kruhlak, Michael J; Misteli, Tom

    2014-12-11

    The DNA damage response (DDR) occurs in the context of chromatin, and architectural features of chromatin have been implicated in DNA damage signaling and repair. Whereas a role of chromatin decondensation in the DDR is well established, we show here that chromatin condensation is integral to DDR signaling. We find that, in response to DNA damage chromatin regions transiently expand before undergoing extensive compaction. Using a protein-chromatin-tethering system to create defined chromatin domains, we show that interference with chromatin condensation results in failure to fully activate DDR. Conversely, forced induction of local chromatin condensation promotes ataxia telangiectasia mutated (ATM)- and ATR-dependent activation of upstream DDR signaling in a break-independent manner. Whereas persistent chromatin compaction enhanced upstream DDR signaling from irradiation-induced breaks, it reduced recovery and survival after damage. Our results demonstrate that chromatin condensation is sufficient for activation of DDR signaling and is an integral part of physiological DDR signaling.

  9. Activity Dependent Signal Transduction in Skeletal Muscle

    NASA Technical Reports Server (NTRS)

    Hamilton, Susan L.

    1999-01-01

    The overall goals of this project are: 1) to define the initial signal transduction events whereby the removal of gravitational load from antigravity muscles, such as the soleus, triggers muscle atrophy, and 2) to develop countermeasures to prevent this from happening. Our rationale for this approach is that, if countermeasures can be developed to regulate these early events, we could avoid having to deal with the multiple cascades of events that occur downstream from the initial event. One of our major findings is that hind limb suspension causes an early and sustained increase in intracellular Ca(2+) concentration ([Ca (2+)](sub i)). In most cells the consequences of changes in ([Ca (2+)](sub i))depend on the amplitude, frequency and duration of the Ca(2+) signal and on other factors in the intracellular environment. We propose that muscle remodeling in microgravity represents a change in the balance among several CA(2+) regulated signal transduction pathways, in particular those involving the transcription factors NFAT and NFkB and the pro-apoptotic protein BAD. Other Ca(2+) sensitive pathways involving PKC, ras, rac, and CaM kinase II may also contribute to muscle remodeling.

  10. Swath sonar mapping of Earth's submarine plate boundaries

    NASA Astrophysics Data System (ADS)

    Carbotte, S. M.; Ferrini, V. L.; Celnick, M.; Nitsche, F. O.; Ryan, W. B. F.

    2014-12-01

    The recent loss of Malaysia Airlines flight MH370 in an area of the Indian Ocean where less than 5% of the seafloor is mapped with depth sounding data (Smith and Marks, EOS 2014) highlights the striking lack of detailed knowledge of the topography of the seabed for much of the worlds' oceans. Advances in swath sonar mapping technology over the past 30 years have led to dramatic improvements in our capability to map the seabed. However, the oceans are vast and only an estimated 10% of the seafloor has been mapped with these systems. Furthermore, the available coverage is highly heterogeneous and focused within areas of national strategic priority and community scientific interest. The major plate boundaries that encircle the globe, most of which are located in the submarine environment, have been a significant focus of marine geoscience research since the advent of swath sonar mapping. While the location of these plate boundaries are well defined from satellite-derived bathymetry, significant regions remain unmapped at the high-resolutions provided by swath sonars and that are needed to study active volcanic and tectonic plate boundary processes. Within the plate interiors, some fossil plate boundary zones, major hotspot volcanoes, and other volcanic provinces have been the focus of dedicated research programs. Away from these major tectonic structures, swath mapping coverage is limited to sparse ocean transit lines which often reveal previously unknown deep-sea channels and other little studied sedimentary structures not resolvable in existing low-resolution global compilations, highlighting the value of these data even in the tectonically quiet plate interiors. Here, we give an overview of multibeam swath sonar mapping of the major plate boundaries of the globe as extracted from public archives. Significant quantities of swath sonar data acquired from deep-sea regions are in restricted-access international archives. Open access to more of these data sets would

  11. Experiments in Coherent Change Detection for Synthetic Aperture Sonar

    DTIC Science & Technology

    2010-06-01

    over time. ACD techniques, long used in airborne radar applications, are just beginning to be applied to sidescan sonar . In Coherent Change Detection...accurate geo- registration), the complexity of the propagation environment, and the radiometric inconsistencies of conventional sidescan sonars ...will follow suit. As conventional sidescan sonars exhibit resolution that degrades with range and are typically limited to creation of backscatter

  12. An autocorrelation model of bat sonar.

    PubMed

    Wiegrebe, Lutz

    2008-06-01

    Their sonar system allows echolocating bats to navigate with high skill through a complex, three- dimensional environment at high speed and low light. The auditory analysis of the echoes of their ultrasonic sounds requires a detailed comparison of the emission and echoes. Here an auditory model of bat sonar is introduced and evaluated against a set of psychophysical phantom-target, echo-acoustic experiments. The model consists of a relatively detailed simulation of auditory peripheral processing in the bat, Phyllostomus discolor, followed by a functional module consisting of a strobed, normalised, autocorrelation in each frequency channel. The model output is accumulated in a sonar image buffer. The model evaluation is based on the comparison of the image-buffer contents generated in individually simulated psychophysical trials. The model provides reasonably good predictions for both temporal and spectral behavioural sonar processing in terms of sonar delay-, roughness, and phase sensitivity and in terms of sensitivity to the temporal separations in two-front targets and the classification of spectrally divergent phantom targets.

  13. Cellular Cholesterol Directly Activates Smoothened in Hedgehog Signaling

    SciTech Connect

    Huang, Pengxiang; Nedelcu, Daniel; Watanabe, Miyako; Jao, Cindy; Kim, Youngchang; Liu, Jing; Salic, Adrian

    2016-08-01

    In vertebrates, sterols are necessary for Hedgehog signaling, a pathway critical in embryogenesis and cancer. Sterols activate the membrane protein Smoothened by binding its extracellular, cysteine-rich domain (CRD). Major unanswered questions concern the nature of the endogenous, activating sterol and the mechanism by which it regulates Smoothened. We report crystal structures of CRD complexed with sterols and alone, revealing that sterols induce a dramatic conformational change of the binding site, which is sufficient for Smoothened activation and is unique among CRD-containing receptors. We demonstrate that Hedgehog signaling requires sterol binding to Smoothened and define key residues for sterol recognition and activity. We also show that cholesterol itself binds and activates Smoothened. Furthermore, the effect of oxysterols is abolished in Smoothened mutants that retain activation by cholesterol and Hedgehog. We propose that the endogenous Smoothened activator is cholesterol, not oxysterols, and that vertebrate Hedgehog signaling controls Smoothened by regulating its access to cholesterol.

  14. Object representation for multi-beam sonar image using local higher-order statistics

    NASA Astrophysics Data System (ADS)

    Li, Haisen; Gao, Jue; Du, Weidong; Zhou, Tian; Xu, Chao; Chen, Baowei

    2017-01-01

    Multi-beam sonar imaging has been widely used in various underwater tasks such as object recognition and object tracking. Problems remain, however, when the sonar images are characterized by low signal-to-noise ratio, low resolution, and amplitude alterations due to viewpoint changes. This paper investigates the capacity of local higher-order statistics (HOS) to represent objects in multi-beam sonar images. The Weibull distribution has been used for modeling the background of the image. Local HOS involving skewness is estimated using a sliding computational window, thus generating the local skewness image of which a square structure is associated with a potential object. The ability of object representation with different signal-to-noise ratio (SNR) between object and background is analyzed, and the choice of the computational window size is discussed. In the case of the object with high SNR, a novel algorithm based on background estimation is proposed to reduce side lobe and retain object regions. The performance of object representation has been evaluated using real data that provided encouraging results in the case of the object with low amplitude, high side lobes, or large fluctuant amplitude. In conclusion, local HOS provides more reliable and stable information relating to the potential object and improves the object representation in multi-beam sonar image.

  15. Tight coordination of aerial flight maneuvers and sonar call production in insectivorous bats.

    PubMed

    Falk, Benjamin; Kasnadi, Joseph; Moss, Cynthia F

    2015-11-01

    Echolocating bats face the challenge of coordinating flight kinematics with the production of echolocation signals used to guide navigation. Previous studies of bat flight have focused on kinematics of fruit and nectar-feeding bats, often in wind tunnels with limited maneuvering, and without analysis of echolocation behavior. In this study, we engaged insectivorous big brown bats in a task requiring simultaneous turning and climbing flight, and used synchronized high-speed motion-tracking cameras and audio recordings to quantify the animals' coordination of wing kinematics and echolocation. Bats varied flight speed, turn rate, climb rate and wingbeat rate as they navigated around obstacles, and they adapted their sonar signals in patterning, duration and frequency in relation to the timing of flight maneuvers. We found that bats timed the emission of sonar calls with the upstroke phase of the wingbeat cycle in straight flight, and that this relationship changed when bats turned to navigate obstacles. We also characterized the unsteadiness of climbing and turning flight, as well as the relationship between speed and kinematic parameters. Adaptations in the bats' echolocation call frequency suggest changes in beam width and sonar field of view in relation to obstacles and flight behavior. By characterizing flight and sonar behaviors in an insectivorous bat species, we find evidence of exquisitely tight coordination of sensory and motor systems for obstacle navigation and insect capture.

  16. Tight coordination of aerial flight maneuvers and sonar call production in insectivorous bats

    PubMed Central

    Falk, Benjamin; Kasnadi, Joseph; Moss, Cynthia F.

    2015-01-01

    ABSTRACT Echolocating bats face the challenge of coordinating flight kinematics with the production of echolocation signals used to guide navigation. Previous studies of bat flight have focused on kinematics of fruit and nectar-feeding bats, often in wind tunnels with limited maneuvering, and without analysis of echolocation behavior. In this study, we engaged insectivorous big brown bats in a task requiring simultaneous turning and climbing flight, and used synchronized high-speed motion-tracking cameras and audio recordings to quantify the animals' coordination of wing kinematics and echolocation. Bats varied flight speed, turn rate, climb rate and wingbeat rate as they navigated around obstacles, and they adapted their sonar signals in patterning, duration and frequency in relation to the timing of flight maneuvers. We found that bats timed the emission of sonar calls with the upstroke phase of the wingbeat cycle in straight flight, and that this relationship changed when bats turned to navigate obstacles. We also characterized the unsteadiness of climbing and turning flight, as well as the relationship between speed and kinematic parameters. Adaptations in the bats' echolocation call frequency suggest changes in beam width and sonar field of view in relation to obstacles and flight behavior. By characterizing flight and sonar behaviors in an insectivorous bat species, we find evidence of exquisitely tight coordination of sensory and motor systems for obstacle navigation and insect capture. PMID:26582935

  17. Bounding the error on bottom estimation for multi-angle swath bathymetry sonar

    NASA Astrophysics Data System (ADS)

    Mullins, Geoff K.; Bird, John S.

    2005-04-01

    With the recent introduction of multi-angle swath bathymetry (MASB) sonar to the commercial marketplace (e.g., Benthos Inc., C3D sonar, 2004), additions must be made to the current sonar lexicon. The correct interpretation of measurements made with MASB sonar, which uses filled transducer arrays to compute angle-of-arrival information (AOA) from backscattered signal, is essential not only for mapping, but for applications such as statistical bottom classification. In this paper it is shown that aside from uncorrelated channel to channel noise, there exists a tradeoff between effects that govern the error bounds on bottom estimation for surfaces having shallow grazing angle and surfaces distributed along a radial arc centered at the transducer. In the first case, as the bottom aligns with the radial direction to the receiver, footprint shift and shallow grazing angle effects dominate the uncertainty in physical bottom position (surface aligns along a single AOA). Alternatively, if signal from a radial arc arrives, a single AOA is usually estimated (not necessarily at the average location of the surface). Through theoretical treatment, simulation, and field measurements, the aforementioned factors affecting MASB bottom mapping are examined. [Work supported by NSERC.

  18. Activation of endothelial β-catenin signaling induces heart failure

    PubMed Central

    Nakagawa, Akito; Naito, Atsuhiko T.; Sumida, Tomokazu; Nomura, Seitaro; Shibamoto, Masato; Higo, Tomoaki; Okada, Katsuki; Sakai, Taku; Hashimoto, Akihito; Kuramoto, Yuki; Oka, Toru; Lee, Jong-Kook; Harada, Mutsuo; Ueda, Kazutaka; Shiojima, Ichiro; Limbourg, Florian P.; Adams, Ralf H.; Noda, Tetsuo; Sakata, Yasushi; Akazawa, Hiroshi; Komuro, Issei

    2016-01-01

    Activation of β-catenin-dependent canonical Wnt signaling in endothelial cells plays a key role in angiogenesis during development and ischemic diseases, however, other roles of Wnt/β-catenin signaling in endothelial cells remain poorly understood. Here, we report that sustained activation of β-catenin signaling in endothelial cells causes cardiac dysfunction through suppressing neuregulin-ErbB pathway in the heart. Conditional gain-of-function mutation of β-catenin, which activates Wnt/β-catenin signaling in Bmx-positive arterial endothelial cells (Bmx/CA mice) led to progressive cardiac dysfunction and 100% mortality at 40 weeks after tamoxifen treatment. Electron microscopic analysis revealed dilatation of T-tubules and degeneration of mitochondria in cardiomyocytes of Bmx/CA mice, which are similar to the changes observed in mice with decreased neuregulin-ErbB signaling. Endothelial expression of Nrg1 and cardiac ErbB signaling were suppressed in Bmx/CA mice. The cardiac dysfunction of Bmx/CA mice was ameliorated by administration of recombinant neuregulin protein. These results collectively suggest that sustained activation of Wnt/β-catenin signaling in endothelial cells might be a cause of heart failure through suppressing neuregulin-ErbB signaling, and that the Wnt/β-catenin/NRG axis in cardiac endothelial cells might become a therapeutic target for heart failure. PMID:27146149

  19. Representational learning for sonar ATR

    NASA Astrophysics Data System (ADS)

    Isaacs, Jason C.

    2014-06-01

    Learned representations have been shown to give hopeful results for solving a multitude of novel learning tasks, even though these tasks may be unknown when the model is being trained. A few notable examples include the techniques of topic models, deep belief networks, deep Boltzmann machines, and local discriminative Gaussians, all inspired by human learning. This self-learning of new concepts via rich generative models has emerged as a promising area of research in machine learning. Although there has been recent progress, existing computational models are still far from being able to represent, identify and learn the wide variety of possible patterns and struc- ture in real-world data. An important issue for further consideration is the use of unsupervised representations for novel underwater target recognition applications. This work will discuss and demonstrate the use of latent Dirichlet allocation and autoencoders for learning unsupervised representations of objects in sonar imagery. The objective is to make these representations more abstract and invariant to noise in the training distribution and improve performance.

  20. Prospects for using sonar for underwater archeology on the Yenisei: surveying a 19th century shipwreck

    NASA Astrophysics Data System (ADS)

    Goncharov, A. E.; Mednikov, D. M.; Karelin, N. M.; Nasyrov, I. R.

    2016-11-01

    Current progress in underwater archeology is based on a rich arsenal of high-tech appliances, among which sonar technology plays a key role; it enables scientists not only to detect submerged archeological objects, but to examine them in high definition without having to conduct diving operations or use expensive underwater unmanned vehicles. While the majority of sensational scientific discoveries using sonar have been made in saltwater environments, freshwater ones, rivers in particular, have seen limited activity. The river Yenisei in central Siberia contains an unrecorded number of shipwrecks that await being discovered and studied. In this article we focus on the peculiarities of using sonar for detecting archeological sites on the Yenisei. This article is based on the results of the 2016 expedition, which has determined the location of Thames, a 19th century British steam schooner which was wrecked on the Yenisei.

  1. Changes in dive behavior during naval sonar exposure in killer whales, long-finned pilot whales, and sperm whales.

    PubMed

    Sivle, L D; Kvadsheim, P H; Fahlman, A; Lam, F P A; Tyack, P L; Miller, P J O

    2012-01-01

    Anthropogenic underwater sound in the environment might potentially affect the behavior of marine mammals enough to have an impact on their reproduction and survival. Diving behavior of four killer whales (Orcinus orca), seven long-finned pilot whales (Globicephala melas), and four sperm whales (Physeter macrocephalus) was studied during controlled exposures to naval sonar [low frequency active sonar (LFAS): 1-2 kHz and mid frequency active sonar (MFAS): 6-7 kHz] during three field seasons (2006-2009). Diving behavior was monitored before, during and after sonar exposure using an archival tag placed on the animal with suction cups. The tag recorded the animal's vertical movement, and additional data on horizontal movement and vocalizations were used to determine behavioral modes. Killer whales that were conducting deep dives at sonar onset changed abruptly to shallow diving (ShD) during LFAS, while killer whales conducting deep dives at the onset of MFAS did not alter dive mode. When in ShD mode at sonar onset, killer whales did not change their diving behavior. Pilot and sperm whales performed normal deep dives (NDD) during MFAS exposure. During LFAS exposures, long-finned pilot whales mostly performed fewer deep dives and some sperm whales performed shallower and shorter dives. Acoustic recording data presented previously indicates that deep diving (DD) is associated with feeding. Therefore, the observed changes in dive behavior of the three species could potentially reduce the foraging efficiency of the affected animals.

  2. Changes in dive behavior during naval sonar exposure in killer whales, long-finned pilot whales, and sperm whales

    PubMed Central

    Sivle, L. D.; Kvadsheim, P. H.; Fahlman, A.; Lam, F. P. A.; Tyack, P. L.; Miller, P. J. O.

    2012-01-01

    Anthropogenic underwater sound in the environment might potentially affect the behavior of marine mammals enough to have an impact on their reproduction and survival. Diving behavior of four killer whales (Orcinus orca), seven long-finned pilot whales (Globicephala melas), and four sperm whales (Physeter macrocephalus) was studied during controlled exposures to naval sonar [low frequency active sonar (LFAS): 1–2 kHz and mid frequency active sonar (MFAS): 6–7 kHz] during three field seasons (2006–2009). Diving behavior was monitored before, during and after sonar exposure using an archival tag placed on the animal with suction cups. The tag recorded the animal's vertical movement, and additional data on horizontal movement and vocalizations were used to determine behavioral modes. Killer whales that were conducting deep dives at sonar onset changed abruptly to shallow diving (ShD) during LFAS, while killer whales conducting deep dives at the onset of MFAS did not alter dive mode. When in ShD mode at sonar onset, killer whales did not change their diving behavior. Pilot and sperm whales performed normal deep dives (NDD) during MFAS exposure. During LFAS exposures, long-finned pilot whales mostly performed fewer deep dives and some sperm whales performed shallower and shorter dives. Acoustic recording data presented previously indicates that deep diving (DD) is associated with feeding. Therefore, the observed changes in dive behavior of the three species could potentially reduce the foraging efficiency of the affected animals. PMID:23087648

  3. Activating Cell Death Ligand Signaling Through Proteasome Inhibition

    DTIC Science & Technology

    2009-05-01

    Activating Cell Death Ligand Signaling Through Proteasome Inhibition PRINCIPAL INVESTIGATOR: Steven R Schwarze...SUBTITLE Activating Cell Death Ligand Signaling Through 5a. CONTRACT NUMBER Proteasome Inhibition 5b. GRANT NUMBER W81XWH-08-1-0392 5c...proteasome inhibition can act as an anti-neoplastic agent in vivo by sensitizing cancer cells to cell death ligands in the tumor microenvironment

  4. Directional Receiver for Biomimetic Sonar System

    NASA Astrophysics Data System (ADS)

    Guarato, Francesco; Andrews, Heather; Windmill, James F.; Jackson, Joseph; Gachagan, Anthony

    An ultrasonic localization method for a sonar system equipped with an emitter and two directional receivers and inspired by bat echolocation uses knowledge of the beam pattern of the receivers to estimate target orientation. Rousettus leschenaultii's left ear constitutes the model for the design of the optimal receiver for this sonar system and 3D printing was used to fabricate receiver structures comprising of two truncated cones with an elliptical external perimeter and a parabolic flare rate in the upper part. Measurements show one receiver has a predominant lobe in the same region and with similar attenuation values as the bat ear model. The final sonar system is to be mounted on vehicular and aerial robots which require remote control for motion and sensors for estimation of each robot's location.

  5. More than the Bottom: Multibeam Sonars and Water-column Imaging (Invited)

    NASA Astrophysics Data System (ADS)

    Mayer, L. A.; Weber, T.; Gardner, J. V.; Malik, M.; Doucet, M.; Beaudoin, J.

    2010-12-01

    The past ten years have seen remarkable advances in our ability to rapidly and accurately map the seafloor. Improvements in sonar design and signal processing have dramatically increased both the spatial and temporal resolution of seafloor mapping systems as well as provided the opportunity to extract information about seafloor character through the concomitant mapping of seafloor backscatter. The latest generation of multibeam sonars, however, can now provide acoustic returns from the water-column as well as from the seafloor. When combined with powerful new visualization tools, the ability to acoustically map large volumes of the water-column opens up vast new areas of application for multibeam sonar data. When applied to the most traditional use of multibeam sonar data (seafloor mapping in support of safe navigation), water-column data afford the opportunity to see small, high-standing targets (like ship’s masts) and offer a powerful tool for critically needed, least-depth detection. Water-column data collected from multibeam sonars also provide numerous opportunities for fisheries research ranging from qualitative descriptions of fish school behavior and vessel avoidance studies (the systems can make measurements well beyond the limited, normal-incidence view of traditional fisheries sonars), to the eventual quantitative measurements of volume backscatter (as systems become more calibrated). Increases in system bandwidth will also open opportunities for target identification studies. With increased bandwith will also come the potential for tuning the systems for the mapping of watermass boundaries, offering a powerful tool for a range of physical oceanographic applications. Finally, the ability to map the water-column has great potential for quantifying the flux of methane into the ocean from natural (and un-natural) seeps. Water-column mapping has already proven a valuable asset in monitoring the Deepwater Horizon well-site for potential blow-outs or gas

  6. Hub-activated signal transmission in complex networks

    NASA Astrophysics Data System (ADS)

    Jahnke, Sven; Memmesheimer, Raoul-Martin; Timme, Marc

    2014-03-01

    A wide range of networked systems exhibit highly connected nodes (hubs) as prominent structural elements. The functional roles of hubs in the collective nonlinear dynamics of many such networks, however, are not well understood. Here, we propose that hubs in neural circuits may activate local signal transmission along sequences of specific subnetworks. Intriguingly, in contrast to previous suggestions of the functional roles of hubs, here, not the hubs themselves, but nonhub subnetworks transfer the signals. The core mechanism relies on hubs and nonhubs providing activating feedback to each other. It may, thus, induce the propagation of specific pulse and rate signals in neuronal and other communication networks.

  7. Signal peptides are allosteric activators of the protein translocase

    PubMed Central

    Gouridis, Giorgos; Karamanou, Spyridoula; Gelis, Ioannis; Kalodimos, Charalampos G.; Economou, Anastassios

    2010-01-01

    Extra-cytoplasmic polypeptides are usually synthesized as “preproteins” carrying aminoterminal, cleavable signal peptides1 and secreted across membranes by translocases. The main bacterial translocase comprises the SecYEG protein-conducting channel and the peripheral ATPase motor SecA2,3. Most proteins destined for the periplasm and beyond are exported post-translationally by SecA2,3. Preprotein targeting to SecA is thought to involve signal peptides4 and chaperones like SecB5,6. Here we reveal that signal peptides have a novel role beyond targeting: they are essential allosteric activators of the translocase. Upon docking on their binding groove on SecA, signal peptides act in trans to drive three successive states: first, “triggering” that drives the translocase to a lower activation energy state; then “trapping” that engages non-native preprotein mature domains docked with high affinity on the secretion apparatus and, finally, “secretion” during which trapped mature domains undergo multiple turnovers of translocation in segments7. A significant contribution by mature domains renders signal peptides less critical in bacterial secretory protein targeting than currently assumed. Rather, it is their function as allosteric activators of the translocase that renders signal peptides essential for protein secretion. A role for signal peptides and targeting sequences as allosteric activators may be universal in protein translocases. PMID:19924216

  8. Signaling Components of Redox Active Endosomes: The Redoxosomes

    PubMed Central

    Oakley, Fredrick D.; Abbott, Duane; Li, Qiang

    2009-01-01

    Abstract Subcellular compartmentalization of reactive oxygen species (ROS) plays a critical role in transmitting cell signals in response to environmental stimuli. In this regard, signals at the plasma membrane have been shown to trigger NADPH oxidase-dependent ROS production within the endosomal compartment and this step can be required for redox-dependent signal transduction. Unique features of redox-active signaling endosomes can include NADPH oxidase complex components (Nox1, Noxo1, Noxa1, Nox2, p47phox, p67phox, and/or Rac1), ROS processing enzymes (SOD1 and/or peroxiredoxins), chloride channels capable of mediating superoxide transport and/or membrane gradients required for Nox activity, and novel redox-dependent sensors that control Nox activity. This review will discuss the cytokine and growth factor receptors that likely mediate signaling through redox-active endosomes, and the common mechanisms whereby they act. Additionally, the review will cover ligand-independent environmental injuries, such as hypoxia/reoxygenation injury, that also appear to facilitate cell signaling through NADPH oxidase at the level of the endosome. We suggest that redox-active endosomes encompass a subset of signaling endosomes that we have termed redoxosomes. Redoxosomes are uniquely equipped with redox-processing proteins capable of transmitting ROS signals from the endosome interior to redox-sensitive effectors on the endosomal surface. In this manner, redoxosomes can control redox-dependent effector functions through the spatial and temporal regulation of ROS as second messengers. Antioxid. Redox Signal. 11, 1313–1333. PMID:19072143

  9. High thresholds for avoidance of sonar by free-ranging long-finned pilot whales (Globicephala melas).

    PubMed

    Antunes, R; Kvadsheim, P H; Lam, F P A; Tyack, P L; Thomas, L; Wensveen, P J; Miller, P J O

    2014-06-15

    The potential effects of exposing marine mammals to military sonar is a current concern. Dose-response relationships are useful for predicting potential environmental impacts of specific operations. To reveal behavioral response thresholds of exposure to sonar, we conducted 18 exposure/control approaches to 6 long-finned pilot whales. Source level and proximity of sonar transmitting one of two frequency bands (1-2 kHz and 6-7 kHz) were increased during exposure sessions. The 2-dimensional movement tracks were analyzed using a changepoint method to identify the avoidance response thresholds which were used to estimate dose-response relationships. No support for an effect of sonar frequency or previous exposures on the probability of response was found. Estimated response thresholds at which 50% of population show avoidance (SPLmax=170 dB re 1 μPa, SELcum=173 dB re 1 μPa(2) s) were higher than previously found for other cetaceans. The US Navy currently uses a generic dose-response relationship to predict the responses of cetaceans to naval active sonar, which has been found to underestimate behavioural impacts on killer whales and beaked whales. The navy curve appears to match more closely our results with long-finned pilot whales, though it might underestimate the probability of avoidance for pilot-whales at long distances from sonar sources.

  10. Cognitive adaptation of sonar gain control in the bottlenose dolphin.

    PubMed

    Kloepper, Laura N; Smith, Adam B; Nachtigall, Paul E; Buck, John R; Simmons, James A; Pacini, Aude F

    2014-01-01

    Echolocating animals adjust the transmit intensity and receive sensitivity of their sonar in order to regulate the sensation level of their echoes; this process is often termed automatic gain control. Gain control is considered not to be under the animal's cognitive control, but previous investigations studied animals ensonifying targets or hydrophone arrays at predictable distances. To test whether animals maintain gain control at a fixed level in uncertain conditions, we measured changes in signal intensity for a bottlenose dolphin (Tursiops truncatus) detecting a target at three target distances (2.5, 4 and 7 m) in two types of sessions: predictable and unpredictable. Predictable sessions presented the target at a constant distance; unpredictable sessions moved the target randomly between the three target positions. In the predictable sessions the dolphin demonstrated intensity distance compensation, increasing the emitted click intensity as the target distance increased. Additionally, as trials within sessions progressed, the animal adjusted its click intensity even from the first click in a click train, which is consistent with the animal expecting a target at a certain range. In the unpredictable sessions there was no significant difference of intensity with target distance until after the 7th click in a click train. Together, these results demonstrate that the bottlenose dolphin uses learning and expectation for sonar gain control.

  11. Cognitive Adaptation of Sonar Gain Control in the Bottlenose Dolphin

    PubMed Central

    Kloepper, Laura N.; Smith, Adam B.; Nachtigall, Paul E.; Buck, John R.; Simmons, James A.; Pacini, Aude F.

    2014-01-01

    Echolocating animals adjust the transmit intensity and receive sensitivity of their sonar in order to regulate the sensation level of their echoes; this process is often termed automatic gain control. Gain control is considered not to be under the animal's cognitive control, but previous investigations studied animals ensonifying targets or hydrophone arrays at predictable distances. To test whether animals maintain gain control at a fixed level in uncertain conditions, we measured changes in signal intensity for a bottlenose dolphin (Tursiops truncatus) detecting a target at three target distances (2.5, 4 and 7 m) in two types of sessions: predictable and unpredictable. Predictable sessions presented the target at a constant distance; unpredictable sessions moved the target randomly between the three target positions. In the predictable sessions the dolphin demonstrated intensity distance compensation, increasing the emitted click intensity as the target distance increased. Additionally, as trials within sessions progressed, the animal adjusted its click intensity even from the first click in a click train, which is consistent with the animal expecting a target at a certain range. In the unpredictable sessions there was no significant difference of intensity with target distance until after the 7th click in a click train. Together, these results demonstrate that the bottlenose dolphin uses learning and expectation for sonar gain control. PMID:25153530

  12. An investigation of acoustic beam patterns for the sonar localization problem using a beam based method.

    PubMed

    Guarato, Francesco; Windmill, James; Gachagan, Anthony; Harvey, Gerald

    2013-06-01

    Target localization can be accomplished through an ultrasonic sonar system equipped with an emitter and two receivers. Time of flight of the sonar echoes allows the calculation of the distance of the target. The orientation can be estimated from knowledge of the beam pattern of the receivers and the ratio, in the frequency domain, between the emitted and the received signals after compensation for distance effects and air absorption. The localization method is described and, as its performance strongly depends on the beam pattern, the search of the most appropriate sonar receiver in order to ensure the highest accuracy of target orientation estimations is developed in this paper. The structure designs considered are inspired by the ear shapes of some bat species. Parameters like flare rate, truncation angle, and tragus are considered in the design of the receiver structures. Simulations of the localization method allow us to state which combination of those parameters could provide the best real world implementation. Simulation results show the estimates of target orientations are, in the worst case, 2° with SNR = 50 dB using the receiver structure chosen for a potential practical implementation of a sonar system.

  13. Coco is a dual activity modulator of TGFβ signaling

    PubMed Central

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

    2015-01-01

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

  14. Coco is a dual activity modulator of TGFβ signaling.

    PubMed

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

    2015-08-01

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

  15. Trajectory Sonar Perception in the Ligurian Sea

    DTIC Science & Technology

    2006-01-01

    A typical marine robot displaces 50-500kg, transmits its sonar 3-10 times per second, and is perturbed by waves with periods on the order of 5-30...Transactions on Pattern Analysis and Machine Intelligence, PAMI-12(6):560–569, June 1990. 2. R. A. Brooks. Cambrian Intelligence: The Early History of the New

  16. Automatic seagrass pattern identification on sonar images

    NASA Astrophysics Data System (ADS)

    Rahnemoonfar, Maryam; Rahman, Abdullah

    2016-05-01

    Natural and human-induced disturbances are resulting in degradation and loss of seagrass. Freshwater flooding, severe meteorological events and invasive species are among the major natural disturbances. Human-induced disturbances are mainly due to boat propeller scars in the shallow seagrass meadows and anchor scars in the deeper areas. Therefore, there is a vital need to map seagrass ecosystems in order to determine worldwide abundance and distribution. Currently there is no established method for mapping the pothole or scars in seagrass. One of the most precise sensors to map the seagrass disturbance is side scan sonar. Here we propose an automatic method which detects seagrass potholes in sonar images. Side scan sonar images are notorious for having speckle noise and uneven illumination across the image. Moreover, disturbance presents complex patterns where most segmentation techniques will fail. In this paper, by applying mathematical morphology technique and calculating the local standard deviation of the image, the images were enhanced and the pothole patterns were identified. The proposed method was applied on sonar images taken from Laguna Madre in Texas. Experimental results show the effectiveness of the proposed method.

  17. Introduction to Sonar, Navy Training Course.

    ERIC Educational Resources Information Center

    Naval Personnel Program Support Activity, Washington, DC.

    Fundamentals of sonar systems are presented in this book, prepared for both regular navy and naval reserve personnel who are seeking advancement in rating. An introductory description is first made of submarines and antisubmarine units. Determination of underwater targets is analyzed from the background of true and relative bearings, true and…

  18. How do tiger moths jam bat sonar?

    PubMed

    Corcoran, Aaron J; Barber, Jesse R; Hristov, Nickolay I; Conner, William E

    2011-07-15

    The tiger moth Bertholdia trigona is the only animal in nature known to defend itself by jamming the sonar of its predators - bats. In this study we analyzed the three-dimensional flight paths and echolocation behavior of big brown bats (Eptesicus fuscus) attacking B. trigona in a flight room over seven consecutive nights to determine the acoustic mechanism of the sonar-jamming defense. Three mechanisms have been proposed: (1) the phantom echo hypothesis, which states that bats misinterpret moth clicks as echoes; (2) the ranging interference hypothesis, which states that moth clicks degrade the bats' precision in determining target distance; and (3) the masking hypothesis, which states that moth clicks mask the moth echoes entirely, making the moth temporarily invisible. On nights one and two of the experiment, the bats appeared startled by the clicks; however, on nights three through seven, the bats frequently missed their prey by a distance predicted by the ranging interference hypothesis (∼15-20 cm). Three-dimensional simulations show that bats did not avoid phantom targets, and the bats' ability to track clicking prey contradicts the predictions of the masking hypothesis. The moth clicks also forced the bats to reverse their stereotyped pattern of echolocation emissions during attack, even while bats continued pursuit of the moths. This likely further hinders the bats' ability to track prey. These results have implications for the evolution of sonar jamming in tiger moths, and we suggest evolutionary pathways by which sonar jamming may have evolved from other tiger moth defense mechanisms.

  19. Tac-beta1 inhibits FAK activation and Src signaling.

    PubMed

    Berrier, Allison L; Jones, Christopher W; LaFlamme, Susan E

    2008-03-28

    The binding of integrins to extracellular matrix triggers signals that promote cell spreading. We previously demonstrated that expression of the integrin beta1 cytoplasmic domain in the context of a chimeric transmembrane receptor with the Tac subunit of the interleukin-2 receptor (Tac-beta1) inhibits cell spreading. To study the mechanism whereby Tac-beta1 inhibits cell spreading, we examined the effect of Tac-beta1 on early signaling events following integrin engagement namely FAK and Src signaling. We infected primary fibroblasts with adenoviruses expressing Tac or Tac-beta1 and found that Tac-beta1 prevented FAK activation by inhibiting the phosphorylation of FAK at Tyr-397. In contrast, Src activation was maintained, as phosphorylation of Src at Tyr-419 and Tyr-530 were not responsive to expression of Tac-beta1. Importantly, adhesion-induced tyrosine phosphorylation of the Src substrates p130Cas and paxillin was inhibited, indicating that Src signaling was blocked by Tac-beta1. These Src-dependent signaling events were found to require FAK signaling. Our results suggest that Tac-beta1 inhibits cell spreading, at least in part, by preventing the phosphorylation of FAK at Tyr-397 and the assembly of signaling complexes necessary for phosphorylation of p130Cas and other downstream effectors.

  20. Assessment of Modeled Received Sound Pressure Levels and Movements of Satellite-Tagged Odontocetes Exposed to Mid-Frequency Active Sonar at the Pacific Missile Range Facility: February 2011 Through February 2013

    DTIC Science & Technology

    2014-05-30

    PMRF so that animal movements and diving behavior could be measured both before and during sonar use. PMRF PAM data and tag data were used in this...initial analysis to estimate exposure levels for tagged animals and determine whether any large-scale movements of these animals may have occurred in...range hydrophones), ship positions at time of transmissions (provided by PMRF) and animal locations (determined from satellite tag positions) allowed

  1. 50 CFR 218.120 - Specified activity and geographical area.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... the following mid-frequency active sonar (MFAS) sources, high-frequency active sonar (HFAS) sources...-mounted active sonar)—up to 2,890 hours over the course of 5 years (an average of 578 hours per year); (ii) AN/SQS-56 (hull-mounted active sonar)—up to 260 hours over the course of 5 years (an average of...

  2. 50 CFR 218.120 - Specified activity and geographical area.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... the following mid-frequency active sonar (MFAS) sources, high-frequency active sonar (HFAS) sources...-mounted active sonar)—up to 2,890 hours over the course of 5 years (an average of 578 hours per year); (ii) AN/SQS-56 (hull-mounted active sonar)—up to 260 hours over the course of 5 years (an average of...

  3. Stra13 regulates satellite cell activation by antagonizing Notch signaling

    PubMed Central

    Sun, Hong; Li, Li; Vercherat, Cécile; Gulbagci, Neriman Tuba; Acharjee, Sujata; Li, Jiali; Chung, Teng-Kai; Thin, Tin Htwe; Taneja, Reshma

    2007-01-01

    Satellite cells play a critical role in skeletal muscle regeneration in response to injury. Notch signaling is vital for satellite cell activation and myogenic precursor cell expansion but inhibits myogenic differentiation. Thus, precise spatial and temporal regulation of Notch activity is necessary for efficient muscle regeneration. We report that the basic helix-loop-helix transcription factor Stra13 modulates Notch signaling in regenerating muscle. Upon injury, Stra13−/− mice exhibit increased cellular proliferation, elevated Notch signaling, a striking regeneration defect characterized by degenerated myotubes, increased mononuclear cells, and fibrosis. Stra13−/− primary myoblasts also exhibit enhanced Notch activity, increased proliferation, and defective differentiation. Inhibition of Notch signaling ex vivo and in vivo ameliorates the phenotype of Stra13−/− mutants. We demonstrate in vitro that Stra13 antagonizes Notch activity and reverses the Notch-imposed inhibition of myogenesis. Thus, Stra13 plays an important role in postnatal myogenesis by attenuating Notch signaling to reduce myoblast proliferation and promote myogenic differentiation. PMID:17502421

  4. Platelet-activating factor: receptors and signal transduction.

    PubMed

    Chao, W; Olson, M S

    1993-06-15

    During the past two decades, studies describing the chemistry and biology of PAF have been extensive. This potent phosphoacylglycerol exhibits a wide variety of physiological and pathophysiological effects in various cells and tissues. PAF acts, through specific receptors and a variety of signal transduction systems, to elicit diverse biochemical responses. Several important future directions can be enumerated for the characterization of PAF receptors and their attendant signalling mechanisms. The recent cloning and sequence analysis of the gene for the PAF receptor will allow a number of important experimental approaches for characterizing the structure and analysing the function of the various domains of the receptor. Using molecular genetic and immunological technologies, questions relating to whether there is receptor heterogeneity, the precise mechanism(s) for the regulation of the PAF receptor, and the molecular details of the signalling mechanisms in which the PAF receptor is involved can be explored. Another area of major significance is the examination of the relationship between the signalling response(s) evoked by PAF binding to its receptor and signalling mechanisms activated by a myriad of other mediators, cytokines and growth factors. A very exciting recent development in which PAF receptors undoubtedly play a role is in the regulation of the function of various cellular adhesion molecules. Finally, there remain many incompletely characterized physiological and pathophysiological situations in which PAF and its receptor play a crucial signalling role. Our laboratory has been active in the elucidation of several tissue responses in which PAF exhibits major autocoid signalling responses, e.g. hepatic injury and inflammation, acute and chronic pancreatitis, and cerebral stimulation and/or trauma. As new experimental strategies are developed for characterizing the fine structure of the molecular mechanisms involved in tissue injury and inflammation, the

  5. Evaluation of the Performance of the Distributed Phased-MIMO Sonar

    PubMed Central

    Pan, Xiang; Jiang, Jingning; Wang, Nan

    2017-01-01

    A broadband signal model is proposed for a distributed multiple-input multiple-output (MIMO) sonar system consisting of two transmitters and a receiving linear array. Transmitters are widely separated to illuminate the different aspects of an extended target of interest. The beamforming technique is utilized at the reception ends for enhancement of weak target echoes. A MIMO detector is designed with the estimated target position parameters within the general likelihood rate test (GLRT) framework. For the high signal-to-noise ratio case, the detection performance of the MIMO system is better than that of the phased-array system in the numerical simulations and the tank experiments. The robustness of the distributed phased-MIMO sonar system is further demonstrated in localization of a target in at-lake experiments. PMID:28085071

  6. Evaluation of the Performance of the Distributed Phased-MIMO Sonar.

    PubMed

    Pan, Xiang; Jiang, Jingning; Wang, Nan

    2017-01-11

    A broadband signal model is proposed for a distributed multiple-input multiple-output (MIMO) sonar system consisting of two transmitters and a receiving linear array. Transmitters are widely separated to illuminate the different aspects of an extended target of interest. The beamforming technique is utilized at the reception ends for enhancement of weak target echoes. A MIMO detector is designed with the estimated target position parameters within the general likelihood rate test (GLRT) framework. For the high signal-to-noise ratio case, the detection performance of the MIMO system is better than that of the phased-array system in the numerical simulations and the tank experiments. The robustness of the distributed phased-MIMO sonar system is further demonstrated in localization of a target in at-lake experiments.

  7. Zinc modulates PPARgamma signaling and activation of porcine endothelial cells.

    PubMed

    Meerarani, Purushothaman; Reiterer, Gudrun; Toborek, Michal; Hennig, Bernhard

    2003-10-01

    Dietary zinc has potent antioxidant and anti-inflammatory properties and is a critical component of peroxisome proliferator-activated receptor (PPAR) gene expression and regulation. To assess the protective mechanisms of PPARgamma in endothelial cell dysfunction and the role of zinc in the modulation of PPARgamma signaling, cultured porcine pulmonary artery endothelial cells were exposed to the membrane-permeable zinc chelator N,N,N'N'-tetrakis (2-pyridylmethyl)-ethylene diamine (TPEN), thiazolidinedione (TZD; PPARgamma agonist) or bisphenol A diglycidyl ether (BADGE; PPARgamma antagonist). Subsequently, endothelial cells were activated by treatment with linoleic acid (90 micro mol/L) for 6 h. Zinc chelation by TPEN increased the DNA binding activity of nuclear factor (NF)-kappaB and activator protein (AP)-1, decreased PPARgamma expression and activation as well as up-regulated interleukin (IL)-6 expression and production. These effects were fully reversed by zinc supplementation. In addition, exposure to TZD down-regulated linoleic acid-induced DNA binding activity of NF-kappaB and AP-1, whereas BADGE further induced activation of these oxidative stress-sensitive transcription factors. Most importantly, the TZD-mediated down-regulation of NF-kappaB and AP-1 and reduced inflammatory response were impaired during zinc chelation. These data suggest that zinc plays a critical role in PPARgamma signaling in linoleic acid-induced endothelial cell activation and indicate that PPARgamma signaling is impaired during zinc deficiency.

  8. Notch signaling promotes osteoclast maturation and resorptive activity

    PubMed Central

    Ashley, Jason W; Ahn, Jaimo; Hankenson, Kurt D

    2015-01-01

    The role of Notch signaling in osteoclast differentiation is controversial with conflicting experimental evidence indicating both stimulatory and inhibitory roles. Differences in experimental protocols and in vivo versus in vitro models may explain the discrepancies between studies. In this study, we investigated cell autonomous roles of Notch signaling in osteoclast differentiation and function by altering Notch signaling during osteoclast differentiation using stimulation with immobilized ligands Jagged1 or Delta-like1 or by suppression with γ-secretase inhibitor DAPT or transcriptional inhibitor SAHM1. Stimulation of Notch signaling in committed osteoclast precursors resulted in larger osteoclasts with a greater number of nuclei and resorptive activity whereas suppression resulted in smaller osteoclasts with fewer nuclei and suppressed resorptive activity. Conversely, stimulation of Notch signaling in osteoclast precursors prior to induction of osteoclastogenesis resulted in fewer osteoclasts. Our data support a mechanism of context-specific Notch signaling effects wherein Notch stimulation inhibits commitment to osteoclast differentiation, but enhances the maturation and function of committed precursors. PMID:25914241

  9. Can the elongated hindwing tails of fluttering moths serve as false sonar targets to divert bat attacks?

    PubMed

    Lee, Wu-Jung; Moss, Cynthia F

    2016-05-01

    It has long been postulated that the elongated hindwing tails of many saturniid moths have evolved to create false sonar targets to divert the attack of echolocation-guided bat predators. However, rigorous echo-acoustic evidence to support this hypothesis has been lacking. In this study, fluttering luna moths (Actias luna), a species with elongated hindwing tails, were ensonified with frequency modulated chirp signals from all angles of orientation and across the wingbeat cycle. High-speed stereo videography was combined with pulse compression sonar processing to characterize the echo information available to foraging bats. Contrary to previous suggestions, the results show that the tail echoes are weak and do not dominate the sonar returns, compared to the large, planar wings and the moth body. However, the distinctive twisted morphology of the tails create persistent echoes across all angles of orientation, which may induce erroneous sonar target localization and disrupt accurate tracking by echolocating bats. These findings thus suggest a refinement of the false target hypothesis to emphasize sonar localization errors induced by the twisted tails, and highlight the importance of physics-based approaches to study the sensory information involved in the evolutionary arms race between moths and their bat predators.

  10. Effects of competitive prey capture on flight behavior and sonar beam pattern in paired big brown bats, Eptesicus fuscus.

    PubMed

    Chiu, Chen; Reddy, Puduru Viswanadha; Xian, Wei; Krishnaprasad, Perinkulam S; Moss, Cynthia F

    2010-10-01

    Foraging and flight behavior of echolocating bats were quantitatively analyzed in this study. Paired big brown bats, Eptesicus fuscus, competed for a single food item in a large laboratory flight room. Their sonar beam patterns and flight paths were recorded by a microphone array and two high-speed cameras, respectively. Bats often remained in nearly classical pursuit (CP) states when one bat is following another bat. A follower can detect and anticipate the movement of the leader, while the leader has the advantage of gaining access to the prey first. Bats in the trailing position throughout the trial were more successful in accessing the prey. In this study, bats also used their sonar beam to monitor the conspecific's movement and to track the prey. Each bat tended to use its sonar beam to track the prey when it was closer to the worm than to another bat. The trailing bat often directed its sonar beam toward the leading bat in following flight. When two bats flew towards each other, they tended to direct their sonar beam axes away from each other, presumably to avoid signal jamming. This study provides a new perspective on how echolocating bats use their biosonar system to coordinate their flight with conspecifics in a group and how they compete for the same food source with conspecifics.

  11. Using side-scan sonar to characterize and map physical habitat and anthropogenic underwater features in the St. Louis River.

    EPA Science Inventory

    Characterizing underwater habitat and other features is difficult and costly, especially in the large St. Louis River Estuary. We are using side-scan sonar (SSS), first developed in the 1960s to remotely sense underwater habitat features from reflected acoustic signals (backscatt...

  12. Relationships between autofocus methods for SAR and self-survey techniques for SONAR. [Synthetic Aperture Radar (SAR)

    SciTech Connect

    Wahl, D.E.; Jakowatz, C.V. Jr.; Ghiglia, D.C.; Eichel, P.H.

    1991-01-01

    Autofocus methods in SAR and self-survey techniques in SONAR have a common mathematical basis in that they both involve estimation and correction of phase errors introduced by sensor position uncertainties. Time delay estimation and correlation methods have been shown to be effective in solving the self-survey problem for towed SONAR arrays. Since it can be shown that platform motion errors introduce similar time-delay estimation problems in SAR imaging, the question arises as to whether such techniques could be effectively employed for autofocus of SAR imagery. With a simple mathematical model for motion errors in SAR, we will show why such correlation/time-delay techniques are not nearly as effective as established SAR autofocus algorithms such as phase gradient autofocus or sub-aperture based methods. This analysis forms an important bridge between signal processing methodologies for SAR and SONAR. 5 refs., 4 figs.

  13. Teaching real-time ultrasonic imaging with a 4-channel sonar array, TI C6711 DSK and MATLAB.

    PubMed

    York, George W P; Welch, Thad B; Wright, Cameron H G

    2005-01-01

    Ultrasonic medical imaging courses often stop at the theory or MATLAB simulation level, since professors find it challenging to give the students the experience of designing a real-time ultrasonic system. Some of the practical problems of working with real-time data from the ultrasonic transducers can be avoided by working at lower frequencies (sonar to low ultrasound) range. To facilitate this, we have created a platform using the ease of MATLAB programming with the real-time processing capability of the low-cost Texas Instruments C6711 DSP starter kit and a 4-channel sonar array. With this platform students can design a B-mode or Color-Mode sonar system in the MATLAB environment. This paper will demonstrate how the platform can be used in the classroom to demonstrate the real-time signal processing stages including beamforming, multi-rate sampling, demodulation, filtering, image processing, echo imaging, and Doppler frequency estimation.

  14. Use of acoustic classification of sidescan sonar data for mapping benthic habitat in the Northern Channel Islands, California

    USGS Publications Warehouse

    Cochrane, Guy R.; Lafferty, Kevin D.

    2002-01-01

    Highly reflective seafloor features imaged by sidescan sonar in nearshore waters off the Northern Channel Islands (California, USA) have been observed in subsequent submersible dives to be areas of thin sand covering bedrock. Adjacent areas of rocky seafloor, suitable as habitat for endangered species of abalone and rockfish, and encrusting organisms, cannot be differentiated from the areas of thin sand on the basis of acoustic backscatter (i.e. grey level) alone. We found second-order textural analysis of sidescan sonar data useful to differentiate the bottom types where data is not degraded by near-range distortion (caused by slant-range and ground-range corrections), and where data is not degraded by far-range signal attenuation. Hand editing based on submersible observations is necessary to completely convert the sidescan sonar image to a bottom character classification map suitable for habitat mapping.

  15. 5'-AMP-activated protein kinase signaling in Caenorhabditis elegans.

    PubMed

    Beale, Elmus G

    2008-01-01

    5'-AMP-activated protein kinase (AMPK) has been called "the metabolic master switch" because of its central role in regulating fuel homeostasis. AMPK, a heterotrimeric serine/threonine protein kinase composed of alpha, beta, and gamma subunits, is activated by upstream kinases and by 5'-AMP in response to various nutritional and stress signals. Downstream effects include regulation of metabolism, protein synthesis, cell growth, and mediation of the actions of a number of hormones, including leptin. However, AMPK research represents a young and growing field; hence, there are many unanswered questions regarding the control and action of AMPK. This review presents evidence for the existence of AMPK signaling pathways in Caenorhabditis elegans, a genetically tractable model organism that has yet to be fully exploited to elucidate AMPK signaling mechanisms.

  16. Suppression of emission rates improves sonar performance by flying bats.

    PubMed

    Adams, Amanda M; Davis, Kaylee; Smotherman, Michael

    2017-01-31

    Echolocating bats face the challenge of actively sensing their environment through their own emissions, while also hearing calls and echoes of nearby conspecifics. How bats mitigate interference is a long-standing question that has both ecological and technological implications, as biosonar systems continue to outperform man-made sonar systems in noisy, cluttered environments. We recently showed that perched bats decreased calling rates in groups, displaying a behavioral strategy resembling the back-off algorithms used in artificial communication networks to optimize information throughput at the group level. We tested whether free-tailed bats (Tadarida brasiliensis) would employ such a coordinated strategy while performing challenging flight maneuvers, and report here that bats navigating obstacles lowered emission rates when hearing artificial playback of another bat's calls. We measured the impact of acoustic interference on navigation performance and show that the calculated reductions in interference rates are sufficient to reduce interference and improve obstacle avoidance. When bats flew in pairs, each bat responded to the presence of the other as an obstacle by increasing emissions, but hearing the sonar emissions of the nearby bat partially suppressed this response. This behavior supports social cohesion by providing a key mechanism for minimizing mutual interference.

  17. Suppression of emission rates improves sonar performance by flying bats

    PubMed Central

    Adams, Amanda M.; Davis, Kaylee; Smotherman, Michael

    2017-01-01

    Echolocating bats face the challenge of actively sensing their environment through their own emissions, while also hearing calls and echoes of nearby conspecifics. How bats mitigate interference is a long-standing question that has both ecological and technological implications, as biosonar systems continue to outperform man-made sonar systems in noisy, cluttered environments. We recently showed that perched bats decreased calling rates in groups, displaying a behavioral strategy resembling the back-off algorithms used in artificial communication networks to optimize information throughput at the group level. We tested whether free-tailed bats (Tadarida brasiliensis) would employ such a coordinated strategy while performing challenging flight maneuvers, and report here that bats navigating obstacles lowered emission rates when hearing artificial playback of another bat’s calls. We measured the impact of acoustic interference on navigation performance and show that the calculated reductions in interference rates are sufficient to reduce interference and improve obstacle avoidance. When bats flew in pairs, each bat responded to the presence of the other as an obstacle by increasing emissions, but hearing the sonar emissions of the nearby bat partially suppressed this response. This behavior supports social cohesion by providing a key mechanism for minimizing mutual interference. PMID:28139707

  18. 50 CFR 216.170 - Specified activity and specified geographical region.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... incidental to the following activities: (1) The use of the following mid-frequency active sonar (MFAS) and high frequency active sonar (HFAS) sources, or similar sources, for Navy training activities (estimated amounts below): (1) The use of the following mid-frequency active sonar (MFAS) and high frequency...

  19. Biased signaling by peptide agonists of protease activated receptor 2.

    PubMed

    Jiang, Yuhong; Yau, Mei-Kwan; Kok, W Mei; Lim, Junxian; Wu, Kai-Chen; Liu, Ligong; Hill, Timothy A; Suen, Jacky Y; Fairlie, David P

    2017-02-07

    Protease activated receptor 2 (PAR2) is associated with metabolism, obesity, inflammatory, respiratory and gastrointestinal disorders, pain, cancer and other diseases. The extracellular N-terminus of PAR2 is a common target for multiple proteases, which cleave it at different sites to generate different N-termini that activate different PAR2-mediated intracellular signaling pathways. There are no synthetic PAR2 ligands that reproduce the same signaling profiles and potencies as proteases. Structure-activity relationships here for 26 compounds spanned a signaling bias over 3 log units, culminating in three small ligands as biased agonist tools for interrogating PAR2 functions. DF253 (2f-LAAAAI-NH2) triggered PAR2-mediated calcium release (EC50 2 μM) but not ERK1/2 phosphorylation (EC50 > 100 μM) in CHO cells transfected with hPAR2. AY77 (Isox-Cha-Chg-NH2) was a more potent calcium-biased agonist (EC50 40 nM, Ca2+; EC50 2 μM, ERK1/2), while its analogue AY254 (Isox-Cha-Chg-A-R-NH2) was an ERK-biased agonist (EC50 2 nM, ERK1/2; EC50 80 nM, Ca2+). Signaling bias led to different functional responses in human colorectal carcinoma cells (HT29). AY254, but not AY77 or DF253, attenuated cytokine-induced caspase 3/8 activation, promoted scratch-wound healing and induced IL-8 secretion, all via PAR2-ERK1/2 signaling. Different ligand components were responsible for different PAR2 signaling and functions, clues that can potentially lead to drugs that modulate different pathway-selective cellular and physiological responses.

  20. Metabolic signals and innate immune activation in obesity and exercise.

    PubMed

    Ringseis, Robert; Eder, Klaus; Mooren, Frank C; Krüger, Karsten

    2015-01-01

    The combination of a sedentary lifestyle and excess energy intake has led to an increased prevalence of obesity which constitutes a major risk factor for several co-morbidities including type 2 diabetes and cardiovascular diseases. Intensive research during the last two decades has revealed that a characteristic feature of obesity linking it to insulin resistance is the presence of chronic low-grade inflammation being indicative of activation of the innate immune system. Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs), being elevated in many obese subjects, through activation of pattern recognition receptors thereby leading to stimulation of critical inflammatory signaling cascades, like IκBα kinase/nuclear factor-κB (IKK/NF- κB), endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and NOD-like receptor P3 (NLRP3) inflammasome pathway, that interfere with insulin signaling. Exercise is one of the main prescribed interventions in obesity management improving insulin sensitivity and reducing obesity- induced chronic inflammation. This review summarizes current knowledge of the cellular recognition mechanisms for FFAs, the inflammatory signaling pathways triggered by excess FFAs in obesity and the counteractive effects of both acute and chronic exercise on obesity-induced activation of inflammatory signaling pathways. A deeper understanding of the effects of exercise on inflammatory signaling pathways in obesity is useful to optimize preventive and therapeutic strategies to combat the increasing incidence of obesity and its comorbidities.

  1. [Activators, receptors and signal transduction pathways of blood platelets].

    PubMed

    Shaturnyĭ, V I; Shakhidzhanov, S S; Sveshnikova, A N; Panteleev, M A

    2014-01-01

    Platelet participation in hemostatic plug formation requires transition into an activated state (or, rather, variety of states) upon action of agonists like ADP, thromboxane A , collagen, thrombin, and others. The mechanisms of action for different agonists, their receptors and signaling pathways associated with them, as well as the mechanisms of platelet response inhibition are the subject of the present review. Collagen exposed upon vessel wall damage induced initial platelet attachment and start of thrombus formation, which involves numerous processes such as aggregation, activation of integrins, granule secretion and increase of intracellular Ca2+. Thrombin, ADP, thromboxane A , and ATP activated platelets that were not initially in contact with the wall and induce additional secretion of activating substances. Vascular endothelium and secretory organs also affect platelet activation, producing both positive (adrenaline) an d negative (prostacyclin, nitric oxide) regulators, thereby determining the relation of activation and inhibition signals, which plays a significant role in the formation of platelet aggregate under normal and pathological conditions. The pathways of platelet signaling are still incompletely understood, and their exploration presents an important objective both for basic cell biology and for the development of new drugs, the methods of diagnostics and of treatment of hemostasis disorders.

  2. Acoustic Image Models for Navigation with Forward-Looking Sonars

    DTIC Science & Technology

    2008-12-01

    used for altitude and velocity over ground estimation. For mapping, the REMUS uses a Marine Sonics 900 kHz sidescan sonar . The Marine Sonics 900 has...and J. Bell. An Automatic Approach to the Detection and Extraction of Mine Features in Sidescan Sonar . IEEE Journal of Oceanic Engineering, 28:90–105...2003. [18] S. Reed, Y. Petillot, and J. Bell. Automated approach to classication of mine-like objects in sidescan sonar using highlight and shadow

  3. Modeling a 300 kHz Bathymetric Sonar System

    DTIC Science & Technology

    1992-09-01

    AD-A257 378 /7 Modeling A 300 kHz Bathymetric Sonar System by Kenneth Alan Malmquist B.S., Drexel University, Philadelphia (1985) Submitted in...Massachusetts Institute of Technology/ Woods Hole Oceanographic Institution 92-28033 Vll1 Nlf • 92 BLANK PAR Modeling A 300 kIz Bathymetric Sonar System by...Deep Submergence Laboratory has developed a family of calibrated high frequency bathymetric sonar systems for underwater survey. It is useful to have a

  4. Flying in silence: Echolocating bats cease vocalizing to avoid sonar jamming

    PubMed Central

    Chiu, Chen; Xian, Wei; Moss, Cynthia F.

    2008-01-01

    Although it has been recognized that echolocating bats may experience jamming from the signals of conspecifics, research on this problem has focused exclusively on time-frequency adjustments in the emitted signals to minimize interference. Here, we report a surprising new strategy used by bats to avoid interference, namely silence. In a quantitative study of flight and vocal behavior of the big brown bat (Eptesicus fuscus), we discovered that the bat spends considerable time in silence when flying with conspecifics. Silent behavior, defined here as at least one bat in a pair ceasing vocalization for more than 0.2 s (200 ms), occurred as much as 76% of the time (mean of 40% across 7 pairs) when their separation was shorter than 1 m, but only 0.08% when a single bat flew alone. Spatial separation, heading direction, and similarity in call design of paired bats were related to the prevalence of this silent behavior. Our data suggest that the bat uses silence as a strategy to avoid interference from sonar vocalizations of its neighbor, while listening to conspecific-generated acoustic signals to guide orientation. Based on previous neurophysiological studies of the bat's auditory midbrain, we hypothesize that environmental sounds (including vocalizations produced by other bats) and active echolocation evoke neural activity in different populations of neurons. Our findings offer compelling evidence that the echolocating bat switches between active and passive sensing to cope with a complex acoustic environment, and these results hold broad implications for research on navigation and communication throughout the animal kingdom. PMID:18725624

  5. Sonar sensor models and their application to mobile robot localization.

    PubMed

    Burguera, Antoni; González, Yolanda; Oliver, Gabriel

    2009-01-01

    This paper presents a novel approach to mobile robot localization using sonar sensors. This approach is based on the use of particle filters. Each particle is augmented with local environment information which is updated during the mission execution. An experimental characterization of the sonar sensors used is provided in the paper. A probabilistic measurement model that takes into account the sonar uncertainties is defined according to the experimental characterization. The experimental results quantitatively evaluate the presented approach and provide a comparison with other localization strategies based on both the sonar and the laser. Some qualitative results are also provided for visual inspection.

  6. The sonar aperture and its neural representation in bats.

    PubMed

    Heinrich, Melina; Warmbold, Alexander; Hoffmann, Susanne; Firzlaff, Uwe; Wiegrebe, Lutz

    2011-10-26

    As opposed to visual imaging, biosonar imaging of spatial object properties represents a challenge for the auditory system because its sensory epithelium is not arranged along space axes. For echolocating bats, object width is encoded by the amplitude of its echo (echo intensity) but also by the naturally covarying spread of angles of incidence from which the echoes impinge on the bat's ears (sonar aperture). It is unclear whether bats use the echo intensity and/or the sonar aperture to estimate an object's width. We addressed this question in a combined psychophysical and electrophysiological approach. In three virtual-object playback experiments, bats of the species Phyllostomus discolor had to discriminate simple reflections of their own echolocation calls differing in echo intensity, sonar aperture, or both. Discrimination performance for objects with physically correct covariation of sonar aperture and echo intensity ("object width") did not differ from discrimination performances when only the sonar aperture was varied. Thus, the bats were able to detect changes in object width in the absence of intensity cues. The psychophysical results are reflected in the responses of a population of units in the auditory midbrain and cortex that responded strongest to echoes from objects with a specific sonar aperture, regardless of variations in echo intensity. Neurometric functions obtained from cortical units encoding the sonar aperture are sufficient to explain the behavioral performance of the bats. These current data show that the sonar aperture is a behaviorally relevant and reliably encoded cue for object size in bat sonar.

  7. Activation of B cells by non-canonical helper signals.

    PubMed

    Cerutti, Andrea; Cols, Montserrat; Puga, Irene

    2012-09-01

    Cognate interaction between T and B lymphocytes of the adaptive immune system is essential for the production of high-affinity antibodies against microbes, and for the establishment of long-term immunological memory. Growing evidence shows that--in addition to presenting antigens to T and B cells--macrophages, dendritic cells and other cells of the innate immune system provide activating signals to B cells, as well as survival signals to antibody-secreting plasma cells. Here, we discuss how these innate immune cells contribute to the induction of highly diversified and temporally sustained antibody responses, both systemically and at mucosal sites of antigen entry.

  8. Molecular hydrogen suppresses activated Wnt/β-catenin signaling

    PubMed Central

    Lin, Yingni; Ohkawara, Bisei; Ito, Mikako; Misawa, Nobuaki; Miyamoto, Kentaro; Takegami, Yasuhiko; Masuda, Akio; Toyokuni, Shinya; Ohno, Kinji

    2016-01-01

    Molecular hydrogen (H2) is effective for many diseases. However, molecular bases of H2 have not been fully elucidated. Cumulative evidence indicates that H2 acts as a gaseous signal modulator. We found that H2 suppresses activated Wnt/β-catenin signaling by promoting phosphorylation and degradation οf β-catenin. Either complete inhibition of GSK3 or mutations at CK1- and GSK3-phosphorylation sites of β-catenin abolished the suppressive effect of H2. H2 did not increase GSK3-mediated phosphorylation of glycogen synthase, indicating that H2 has no direct effect on GSK3 itself. Knock-down of adenomatous polyposis coli (APC) or Axin1, which form the β-catenin degradation complex, minimized the suppressive effect of H2 on β-catenin accumulation. Accordingly, the effect of H2 requires CK1/GSK3-phosphorylation sites of β-catenin, as well as the β-catenin degradation complex comprised of CK1, GSK3, APC, and Axin1. We additionally found that H2 reduces the activation of Wnt/β-catenin signaling in human osteoarthritis chondrocytes. Oral intake of H2 water tended to ameliorate cartilage degradation in a surgery-induced rat osteoarthritis model through attenuating β-catenin accumulation. We first demonstrate that H2 suppresses abnormally activated Wnt/β-catenin signaling, which accounts for the protective roles of H2 in a fraction of diseases. PMID:27558955

  9. Color and Grey Scale in Sonar Displays

    NASA Technical Reports Server (NTRS)

    Kraiss, K. F.; Kuettelwesch, K. H.

    1984-01-01

    In spite of numerous publications 1 it is still rather unclear, whether color is of any help in sonar displays. The work presented here deals with a particular type of sonar data, i.e., LOFAR-grams (low frequency analysing and recording) where acoustic sensor data are continuously written as a time-frequency plot. The question to be answered quantitatively is, whether color coding does improve target detection when compared with a grey scale code. The data show significant differences in receiver-operating characteristics performance for the selected codes. In addition it turned out, that the background noise level affects the performance dramatically for some color codes, while others remain stable or even improve. Generally valid rules are presented on how to generate useful color scales for this particular application.

  10. BMP2 Transfer to Neighboring Cells and Activation of Signaling.

    PubMed

    Alborzinia, Hamed; Shaikhkarami, Marjan; Hortschansky, Peter; Wölfl, Stefan

    2016-09-01

    Morphogen gradients and concentration are critical features during early embryonic development and cellular differentiation. Previously we reported the preparation of biologically active, fluorescently labeled BMP2 and quantitatively analyzed their binding to the cell surface and followed BMP2 endocytosis over time on the level of single endosomes. Here we show that this internalized BMP2 can be transferred to neighboring cells and, moreover, also activates downstream BMP signaling in adjacent cells, indicated by Smad1/5/8 phosphorylation and activation of the downstream target gene id1. Using a 3D matrix to modulate cell-cell contacts in culture we could show that direct cell-cell contact significantly increased BMP2 transfer. Using inhibitors of vesicular transport, transfer was strongly inhibited. Interestingly, cotreatment with the physiological BMP inhibitor Noggin increased BMP2 uptake and transfer, albeit activation of Smad signaling in neighboring cells was completely suppressed. Our findings present a novel and interesting mechanism by which morphogens such as BMP2 can be transferred between cells and how this is modulated by BMP antagonists such as Noggin, and how this influences activation of Smad signaling by BMP2 in neighboring cells.

  11. 75 FR 79342 - Taking and Importing Marine Mammals; Navy Training Activities Conducted Within the Northwest...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... exposing them to sound from mid-frequency or high frequency active sonar (MFAS/HFAS) or to underwater... frequency active sonar (MFAS/HFAS) or underwater detonations. After submitting supplemental...

  12. Regulation of Chemokine Signal Integration by Activator of G-Protein Signaling 4 (AGS4)

    PubMed Central

    Robichaux, William G.; Branham-O’Connor, Melissa; Hwang, Il-Young; Vural, Ali; Kehrl, Johne H.

    2017-01-01

    Activator of G-protein signaling 4 (AGS4)/G-protein signaling modulator 3 (Gpsm3) contains three G-protein regulatory (GPR) motifs, each of which can bind Gαi-GDP free of Gβγ. We previously demonstrated that the AGS4-Gαi interaction is regulated by seven transmembrane-spanning receptors (7-TMR), which may reflect direct coupling of the GPR-Gαi module to the receptor analogous to canonical Gαβγ heterotrimer. We have demonstrated that the AGS4-Gαi complex is regulated by chemokine receptors in an agonist-dependent manner that is receptor-proximal. As an initial approach to investigate the functional role(s) of this regulated interaction in vivo, we analyzed leukocytes, in which AGS4/Gpsm3 is predominantly expressed, from AGS4/Gpsm3-null mice. Loss of AGS4/Gpsm3 resulted in mild but significant neutropenia and leukocytosis. Dendritic cells, T lymphocytes, and neutrophils from AGS4/Gpsm3-null mice also exhibited significant defects in chemoattractant-directed chemotaxis and extracellular signal-regulated kinase activation. An in vivo peritonitis model revealed a dramatic reduction in the ability of AGS4/Gpsm3-null neutrophils to migrate to primary sites of inflammation. Taken together, these data suggest that AGS4/Gpsm3 is required for proper chemokine signal processing in leukocytes and provide further evidence for the importance of the GPR-Gαi module in the regulation of leukocyte function. PMID:28062526

  13. Behavior of captive herring exposed to naval sonar transmissions (1.0-1.6 kHz) throughout a yearly cycle.

    PubMed

    Doksæter, Lise; Handegard, Nils Olav; Godø, Olav Rune; Kvadsheim, Petter H; Nordlund, Nina

    2012-02-01

    Atlantic herring, Clupea harengus, is a hearing specialist, and several studies have demonstrated strong responses to man-made noise, for example, from an approaching vessel. To avoid negative impacts from naval sonar operations, a set of studies of reaction patters of herring to low-frequency (1.0-1.5 kHz) naval sonar signals has been undertaken. This paper presents herring reactions to sonar signals and other stimuli when kept in captivity under detailed acoustic and video monitoring. Throughout the experiment, spanning three seasons of a year, the fish did not react significantly to sonar signals from a passing frigate, at received root-mean-square sound-pressure level (SPL) up to 168 dB re 1 μPa. In contrast, the fish did exhibit a significant diving reaction when exposed to other sounds, with a much lower SPL, e.g., from a two-stroke engine. This shows that the experimental setup is sensitive to herring reactions when occurring. The lack of herring reaction to sonar signals is consistent with earlier in situ behavioral studies. The complexity of the behavioral reactions in captivity underline the need for better understanding of the causal relationship between stimuli and reaction patterns of fish.

  14. Mapping with side-scan sonar

    SciTech Connect

    Prior, D.B.; Coleman, J.M.; Roberts, H.H.

    1981-04-01

    The use of sideways scanning sonar as a technique for detailed sea-floor mapping is described in this article. Sea-floor mapping of the continental shelf is becoming increasingly necessary for the development of oil and gas resources. More recently attempts are being made to extend the survey capabilities to deeper water shelf margins, slopes, and basins. Conventional systems, digital systems, survey ranges, data processing, mosaics, and applications are discussed. (DMC)

  15. Sonar Transducer Reliability Improvement Program (STRIP).

    DTIC Science & Technology

    1981-04-01

    surfaces of PZT ceramic. The ceramic surface tends to be the weakest part of the insulation system of a sonar transducer. The highest typical electrical...comparable value obtained with uncoated ceramic. Also, the breakdown voltage on the surface ( flashover ) was increased only a small amount, typically less...coating/ surface interface, and some were combinations. A coating material often touted as exceptionally 3ood is Parylene, which is vacuum deposited

  16. Sonar Transducer Reliability Improvement Program FY80.

    DTIC Science & Technology

    1980-01-01

    band Threshold - less than ±2 dB variation from the specified value over operational frequency band The Sonar Transducer Reliability Improvement...were Qetiker preformed clamps, Band -It preformed clamps, and Band -It Scru-Loct retrofittable clamps. *TASK 5: Manufacture Instrumented Connectors Under...cycle 6 PRE-kORM 10 PU-U Cable bond failure, Remove from test after DSS-3 under gap in clamp cycle 5 OETIKER 11 N-G " ring leakage was Removed from

  17. Field Calibration Procedures for Multibeam Sonar Systems

    DTIC Science & Technology

    1998-06-01

    include multibeam sonar transducers, light detection and ranging ( LIDAR ) surveys, acoustic seafloor classification systems, sub-bottom profilers, and... DTM ) of the reference surface is created from the cleaned data, and an averaging gridding algorithm is used to smooth the data. The gridding size...should be no larger than the average footprint of the inner beams. Using large vertical exaggeration, the DTM should be observed on 3-D visualization

  18. Velocity Estimation Using Forward Looking Sonar

    DTIC Science & Technology

    2007-03-01

    Looking Sonar GPS Global Positioning System GWOT Global War on Terrorism ISR Intelligence, Surveillance, and Reconnaissance LBL Long Base-Line NL...inputs from equipment such as long base-line ( LBL ) transponders, accelerometers, and gyroscopes to track how the vehicle has moved from the last known...includes a compass, the above-mentioned ADCP to provide speed over ground when ground lock is available, and an acoustic LBL system to correct

  19. Radar and sonar probing of rocks

    SciTech Connect

    Unterberger, R.R.

    1983-03-01

    The purpose of this paper is to summarize the research of the past sixteen years on methods of probing into solid rock. For these purposes, there are three completely different systems: radar, sonar, and nonlinear sonar. In dry salt all of the systems work. Five radar systems of different frequencies have been used to probe salt for different purposes and with different resolutions. Distances penetrated were from almost 2000 meters to under one 1 meter. With some moisture in the rock, the low frequency Alpha radar system is best because it operates at the frequency of the minimum in loss tangent for water. Sonar systems are used for even more water in the rock. Ranges of one to 300 meters have been obtained in salt with the lower ranges (to 100m) being obtainable is salt with the most water in it. Using one or more of the probing systems, the authors have detected, and ranged to, salt dome flanks, the top of salt, sandstone, anhydrite and sylvite stringers in salt, fractures in salt and water-filled fractures. We have also detected old boreholes in salt pillars, and measured the range and direction to them.

  20. Measurement of stream channel habitat using sonar

    USGS Publications Warehouse

    Flug, M.; Seitz, H.; Scott, J.

    1998-01-01

    An efficient and low cost technique using a sonar system was evaluated for describing channel geometry and quantifying inundated area in a large river. The boat-mounted portable sonar equipment was used to record water depths and river width measurements for direct storage on a laptop computer. The field data collected from repeated traverses at a cross-section were evaluated to determine the precision of the system and field technique. Results from validation at two different sites showed average sample standard deviations (S.D.s) of 0.12 m for these complete cross-sections, with coefficient of variations of 10%. Validation using only the mid-channel river cross-section data yields an average sample S.D. of 0.05 m, with a coefficient of variation below 5%, at a stable and gauged river site using only measurements of water depths greater than 0.6 m. Accuracy of the sonar system was evaluated by comparison to traditionally surveyed transect data from a regularly gauged site. We observed an average mean squared deviation of 46.0 cm2, considering only that portion of the cross-section inundated by more than 0.6 m of water. Our procedure proved to be a reliable, accurate, safe, quick, and economic method to record river depths, discharges, bed conditions, and substratum composition necessary for stream habitat studies. ?? 1998 John Wiley & Sons, Ltd.

  1. 50 CFR 216.240 - Specified activity and specified geographical region.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Active Sonar Training (AFAST) § 216.240 Specified activity and specified geographical region. (a... Navy is only authorized if it occurs incidental to the use of the following mid-frequency active sonar (MFAS) sources, high frequency active sonar (HFAS) sources, explosive sonobuoys, or similar sources,...

  2. 50 CFR 216.240 - Specified activity and specified geographical region.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Active Sonar Training (AFAST) § 216.240 Specified activity and specified geographical region. (a... Navy is only authorized if it occurs incidental to the use of the following mid-frequency active sonar (MFAS) sources, high frequency active sonar (HFAS) sources, explosive sonobuoys, or similar sources,...

  3. Energetics of neuronal signaling and fMRI activity.

    PubMed

    Maandag, Natasja J G; Coman, Daniel; Sanganahalli, Basavaraju G; Herman, Peter; Smith, Arien J; Blumenfeld, Hal; Shulman, Robert G; Hyder, Fahmeed

    2007-12-18

    Energetics of resting and evoked fMRI signals were related to localized ensemble firing rates (nu) measured by electrophysiology in rats. Two different unstimulated, or baseline, states were established by anesthesia. Halothane and alpha-chloralose established baseline states of high and low energy, respectively, in which forepaw stimulation excited the contralateral primary somatosensory cortex (S1). With alpha-chloralose, forepaw stimulation induced strong and reproducible fMRI activations in the contralateral S1, where the ensemble firing was dominated by slow signaling neurons (SSN; nu range of 1-13 Hz). Under halothane, weaker and less reproducible fMRI activations were observed in the contralateral S1 and elsewhere in the cortex, but ensemble activity in S1 was dominated by rapid signaling neurons (RSN; nu range of 13-40 Hz). For both baseline states, the RSN activity (i.e., higher frequencies, including the gamma band) did not vary upon stimulation, whereas the SSN activity (i.e., alpha band and lower frequencies) did change. In the high energy baseline state, a large majority of total oxidative energy [cerebral metabolic rate of oxygen consumption (CMR(O2))] was devoted to RSN activity, whereas in the low energy baseline state, it was roughly divided between SSN and RSN activities. We hypothesize that in the high energy baseline state, the evoked changes in fMRI activation in areas beyond S1 are supported by rich intracortical interactions represented by RSN. We discuss implications for interpreting fMRI data where stimulus-specific DeltaCMR(O2) is generally small compared with baseline CMR(O2).

  4. Dynamic Hedgehog signalling pathway activity in germline stem cells.

    PubMed

    Sahin, Z; Szczepny, A; McLaughlin, E A; Meistrich, M L; Zhou, W; Ustunel, I; Loveland, K L

    2014-03-01

    Although the contribution of Hedgehog (Hh) signalling to stem cell development and oncogenesis is well recognised, its importance for spermatogonial stem cells (SSCs) has not been established. Here we interrogate adult rat SSCs using an established model in which only undifferentiated spermatogonial cells remain in the testis at 15 weeks following irradiation, and spermatogonial differentiation is induced within 4 weeks by gonadotrophin-releasing hormone antagonist (GnRH-ant) administration. Synthesis of Hh pathway components in untreated adult rat testes was compared with that in irradiated testes prior to and after GnRH-ant exposure using in situ hybridization. In adult testes with complete spermatogenesis, the Desert Hedgehog ligand transcript, Dhh, was detected in Sertoli cells, some spermatogonia and in spermatocytes by in situ hybridization. Spermatogenic cells were identified as sites of Hh signalling through detection of transcripts encoding the Hh receptor, Ptc2 transcripts and proteins for the key downstream target of Hh signalling, Gli1 and the Hh transcriptional activator, Gli2. Remarkably, the undifferentiated spermatogonia present in irradiated adult rat testes contained Dhh in addition to Ptc2, Gli1 and Gli2, revealing the potential for an autocrine Hh signalling loop to sustain undifferentiated spermatogonial cells. These transcripts became undetectable by in situ hybridization following GnRH-ant induction of spermatogonial differentiation, however, detection of Gli1 protein in spermatogonia in all groups indicates that Hh signalling is sustained. This is the first evidence of active Hh signalling in mammalian male germline stem cells, as has been documented for some cancer stem cells.

  5. Different activation signals induce distinct mast cell degranulation strategies

    PubMed Central

    Sibilano, Riccardo; Marichal, Thomas; Reber, Laurent L.; Cenac, Nicolas; McNeil, Benjamin D.; Dong, Xinzhong; Hernandez, Joseph D.; Sagi-Eisenberg, Ronit; Hammel, Ilan; Roers, Axel; Valitutti, Salvatore; Tsai, Mindy

    2016-01-01

    Mast cells (MCs) influence intercellular communication during inflammation by secreting cytoplasmic granules that contain diverse mediators. Here, we have demonstrated that MCs decode different activation stimuli into spatially and temporally distinct patterns of granule secretion. Certain signals, including substance P, the complement anaphylatoxins C3a and C5a, and endothelin 1, induced human MCs rapidly to secrete small and relatively spherical granule structures, a pattern consistent with the secretion of individual granules. Conversely, activating MCs with anti-IgE increased the time partition between signaling and secretion, which was associated with a period of sustained elevation of intracellular calcium and formation of larger and more heterogeneously shaped granule structures that underwent prolonged exteriorization. Pharmacological inhibition of IKK-β during IgE-dependent stimulation strongly reduced the time partition between signaling and secretion, inhibited SNAP23/STX4 complex formation, and switched the degranulation pattern into one that resembled degranulation induced by substance P. IgE-dependent and substance P–dependent activation in vivo also induced different patterns of mouse MC degranulation that were associated with distinct local and systemic pathophysiological responses. These findings show that cytoplasmic granule secretion from MCs that occurs in response to different activating stimuli can exhibit distinct dynamics and features that are associated with distinct patterns of MC-dependent inflammation. PMID:27643442

  6. Small molecule activation of NOTCH signaling inhibits acute myeloid leukemia

    PubMed Central

    Ye, Qi; Jiang, Jue; Zhan, Guanqun; Yan, Wanyao; Huang, Liang; Hu, Yufeng; Su, Hexiu; Tong, Qingyi; Yue, Ming; Li, Hua; Yao, Guangmin; Zhang, Yonghui; Liu, Hudan

    2016-01-01

    Aberrant activation of the NOTCH signaling pathway is crucial for the onset and progression of T cell leukemia. Yet recent studies also suggest a tumor suppressive role of NOTCH signaling in acute myeloid leukemia (AML) and reactivation of this pathway offers an attractive opportunity for anti-AML therapies. N-methylhemeanthidine chloride (NMHC) is a novel Amaryllidaceae alkaloid that we previously isolated from Zephyranthes candida, exhibiting inhibitory activities in a variety of cancer cells, particularly those from AML. Here, we report NMHC not only selectively inhibits AML cell proliferation in vitro but also hampers tumor development in a human AML xenograft model. Genome-wide gene expression profiling reveals that NMHC activates the NOTCH signaling. Combination of NMHC and recombinant human NOTCH ligand DLL4 achieves a remarkable synergistic effect on NOTCH activation. Moreover, pre-inhibition of NOTCH by overexpression of dominant negative MAML alleviates NMHC-mediated cytotoxicity in AML. Further mechanistic analysis using structure-based molecular modeling as well as biochemical assays demonstrates that NMHC docks in the hydrophobic cavity within the NOTCH1 negative regulatory region (NRR), thus promoting NOTCH1 proteolytic cleavage. Our findings thus establish NMHC as a potential NOTCH agonist that holds great promises for future development as a novel agent beneficial to patients with AML. PMID:27211848

  7. Cherry Valley Ducks Mitochondrial Antiviral-Signaling Protein-Mediated Signaling Pathway and Antiviral Activity Research

    PubMed Central

    Li, Ning; Hong, Tianqi; Li, Rong; Wang, Yao; Guo, Mengjiao; Cao, Zongxi; Cai, Yumei; Liu, Sidang; Chai, Tongjie; Wei, Liangmeng

    2016-01-01

    Mitochondrial antiviral-signaling protein (MAVS), an adaptor protein of retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs)-mediated signal pathway, is involved in innate immunity. In this study, Cherry Valley duck MAVS (duMAVS) was cloned from the spleen and analyzed. duMAVS was determined to have a caspase activation and recruitment domain at N-terminal, followed by a proline-rich domain and a transmembrane domain at C-terminal. Quantitative real-time PCR indicated that duMAVS was expressed in all tissues tested across a broad expression spectrum. The expression of duMAVS was significantly upregulated after infection with duck Tembusu virus (DTMUV). Overexpression of duMAVS could drive the activation of interferon (IFN)-β, nuclear factor-κB, interferon regulatory factor 7, and many downstream factors (such as Mx, PKR, OAS, and IL-8) in duck embryo fibroblast cells. What is more, RNA interference further confirmed that duMAVS was an important adaptor for IFN-β activation. The antiviral assay showed that duMAVS could suppress the various viral replications (DTMUV, novel reovirus, and duck plague virus) at early stages of infection. Overall, these results showed that the main signal pathway mediated by duMAVS and it had a broad-spectrum antiviral ability. This research will be helpful to better understanding the innate immune system of ducks. PMID:27708647

  8. Dynorphin Activates Quorum Sensing Quinolone Signaling in Pseudomonas aeruginosa

    PubMed Central

    Zaborina, Olga; Lepine, Francois; Xiao, Gaoping; Valuckaite, Vesta; Chen, Yimei; Li, Terry; Ciancio, Mae; Zaborin, Alex; Petroff, Elaine; Turner, Jerrold R; Rahme, Laurence G; Chang, Eugene; Alverdy, John C

    2007-01-01

    There is now substantial evidence that compounds released during host stress directly activate the virulence of certain opportunistic pathogens. Here, we considered that endogenous opioids might function as such compounds, given that they are among the first signals to be released at multiple tissue sites during host stress. We tested the ability of various opioid compounds to enhance the virulence of Pseudomonas aeruginosa using pyocyanin production as a biological readout, and demonstrated enhanced virulence when P. aeruginosa was exposed to synthetic (U-50,488) and endogenous (dynorphin) κ-agonists. Using various mutants and reporter strains of P. aeruginosa, we identified involvement of key elements of the quorum sensing circuitry such as the global transcriptional regulator MvfR and the quorum sensing-related quinolone signaling molecules PQS, HHQ, and HQNO that respond to κ-opioids. The in vivo significance of κ-opioid signaling of P. aeruginosa was demonstrated in mice by showing that dynorphin is released from the intestinal mucosa following ischemia/reperfusion injury, activates quinolone signaling in P. aeruginosa, and enhances the virulence of P. aeruginosa against Lactobacillus spp. and Caenorhabditis elegans. Taken together, these data demonstrate that P. aeruginosa can intercept opioid compounds released during host stress and integrate them into core elements of quorum sensing circuitry leading to enhanced virulence. PMID:17367209

  9. Plant PRRs and the activation of innate immune signaling.

    PubMed

    Macho, Alberto P; Zipfel, Cyril

    2014-04-24

    Despite being sessile organisms constantly exposed to potential pathogens and pests, plants are surprisingly resilient to infections. Plants can detect invaders via the recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). Plant PRRs are surface-localized receptor-like kinases, which comprise a ligand-binding ectodomain and an intracellular kinase domain, or receptor-like proteins, which do not exhibit any known intracellular signaling domain. In this review, we summarize recent discoveries that shed light on the molecular mechanisms underlying ligand perception and subsequent activation of plant PRRs. Notably, plant PRRs appear as central components of multiprotein complexes at the plasma membrane that contain additional transmembrane and cytosolic kinases required for the initiation and specificity of immune signaling. PRR complexes are under tight control by protein phosphatases, E3 ligases, and other regulatory proteins, illustrating the exquisite and complex regulation of these molecular machines whose proper activation underlines a crucial layer of plant immunity.

  10. Processing and analysis of Simrad multibeam sonar data

    NASA Astrophysics Data System (ADS)

    Mitchell, Neil C.

    1996-12-01

    The common approach to analysing data collected with multibeam and sidescan sonars is to visually interpret charts of contoured bathymetry and mosaics of seabed images. However, some of the information content is lost by processing the data into charts because this involves some averaging; the analysis might uncover more information if done on the data at an earlier stage in the processing. Motivated by this potential, I have created a software system which can be used to analyse data collected with Simrad EM1000 (shallow water) and EM12 (deep water) multibeam sonars, as well as to generate bathymetry contour charts and backscatter mosaics. The system includes data preprocessing, such as navigation filtering, depth filtering (removal of outlying values), and amplitude mapping using the multibeam bathymetry to correctly position image pixels across the swath. The data attributes that can be analysed include the orientation and slope of the seafloor, and the mean signal strength for each sounding. To determine bathymetry attributes such as slope, the soundings across a number of beams and across a series of pings are grouped and a least-squares plane fitted to them. Bathymetric curvature is obtained by detrending the grouped data using the least-squares plane and fitting a paraboloid to the residuals. The magnitudes and signs of the paraboloid's coefficients reveal depressions and hills and their orientations. Furthermore, the seafloor geology can be classified using a simple combination of these attributes. For example, flat-lying sediments can be classified where the backscatter, slope and curvature fall below specified values.

  11. Structure-activity analysis of the Pseudomonas quinolone signal molecule.

    PubMed

    Hodgkinson, James; Bowden, Steven D; Galloway, Warren R J D; Spring, David R; Welch, Martin

    2010-07-01

    We synthesized a range of PQS (Pseudomonas quinolone signal; 2-heptyl-3-hydroxy-4(1H)-quinolone) analogues and tested them for their ability to stimulate MvfR-dependent pqsA transcription, MvfR-independent pyoverdine production, and membrane vesicle production. The structure-activity profile of the PQS analogues was different for each of these phenotypes. Certain inactive PQS analogues were also found to strongly synergize PQS-dependent pyoverdine production.

  12. Chemical Signaling and Functional Activation in Colloidosome-Based Protocells.

    PubMed

    Sun, Shiyong; Li, Mei; Dong, Faqin; Wang, Shengjie; Tian, Liangfei; Mann, Stephen

    2016-04-13

    An aqueous-based microcompartmentalized model involving the integration of partially hydrophobic Fe(III)-rich montmorillonite (FeM) clay particles as structural and catalytic building blocks for colloidosome membrane assembly, self-directed membrane remodeling, and signal-induced protocell communication is described. The clay colloidosomes exhibit size- and charge-selective permeability, and show dual catalytic functions involving spatially confined enzyme-mediated dephosphorylation and peroxidase-like membrane activity. The latter is used for the colloidosome-mediated synthesis and assembly of a temperature-responsive poly(N-isopropylacrylamide)(PNIPAM)/clay-integrated hybrid membrane. In situ PNIPAM elaboration of the membrane is coupled to a glucose oxidase (GOx)-mediated signaling pathway to establish a primitive model of chemical communication and functional activation within a synthetic "protocell community" comprising a mixed population of GOx-containing silica colloidosomes and alkaline phosphatase (ALP)-containing FeM-clay colloidosomes. Triggering the enzyme reaction in the silica colloidosomes gives a hydrogen peroxide signal that induces polymer wall formation in a coexistent population of the FeM-clay colloidosomes, which in turn generates self-regulated membrane-gated ALP-activity within the clay microcompartments. The emergence of new functionalities in inorganic colloidosomes via chemical communication between different protocell populations provides a first step toward the realization of interacting communities of synthetic functional microcompartments.

  13. Implications of mitogen-activated protein kinase signaling in glioma.

    PubMed

    Pandey, Vimal; Bhaskara, Vasantha Kumar; Babu, Phanithi Prakash

    2016-02-01

    Gliomas are the most common primary central nervous system tumors. Gliomas originate from astrocytes, oligodendrocytes, and neural stem cells or their precursors. According to WHO classification, gliomas are classified into four different malignant grades ranging from grade I to grade IV based on histopathological features and related molecular aberrations. The induction and maintenance of these tumors can be attributed largely to aberrant signaling networks. In this regard, the mitogen-activated protein kinase (MAPK) network has been widely studied and is reported to be severely altered in glial tumors. Mutations in MAPK pathways most frequently affect RAS and B-RAF in the ERK, c-Jun N-terminal kinase (JNK), and p38 pathways leading to malignant transformation. Also, it is linked to both inherited and sequential accumulations of mutations that control receptor tyrosine kinase (RTK)-activated signal transduction pathways, cell cycle growth arrest pathways, and nonresponsive cell death pathways. Genetic alterations that modulate RTK signaling can also alter several downstream pathways, including RAS-mediated MAP kinases along with JNK pathways, which ultimately regulate cell proliferation and cell death. The present review focuses on recent literature regarding important deregulations in the RTK-activated MAPK pathway during gliomagenesis and progression.

  14. Neural mechanisms underlying the analysis of sonar and social vocalizations: Spectral and temporal integration in the mustached bat

    NASA Astrophysics Data System (ADS)

    Wenstrup, Jeffrey J.; Nataraj, Kiran; Gans, Don; Sheykholeslami, Kianoush

    2004-05-01

    The analysis of sonar echoes by the mustached bat depends on combination-sensitive neurons that respond best when distinct spectral elements of a sonar pulse and echo occur in a particular temporal relationship. Such integrative response properties underlie direct comparisons of acoustic features in outgoing pulses and returning echoes, comparisons thought to encode pulse-echo delay and other information-bearing features of echoes. These response properties are abundant in the auditory midbrain, thalamus, and cortex of the mustached bat. Combination-sensitive neurons utilize facilitatory and inhibitory neural interactions to create selective responses to acoustic features. The different interactions (facilitatory and inhibitory) originate in different stages within the ascending auditory pathway. Inhibitory interactions arise mostly in the auditory brainstem. Facilitatory interactions arise within the inferior colliculus, but also display the results of the inhibitory interactions originating at brainstem levels. These response properties are well suited to the analysis of sonar echoes, but similar combinatorial response properties are tuned to spectral elements outside sonar frequency bands, probably to elements of social vocalizations. It is therefore likely that the neural analysis of biosonar signals shares common features with the analysis of other vocal signals. [Work supported by the National Institute on Deafness and Other Communication Disorders.

  15. Processing of SeaMARC swath sonar imagery

    SciTech Connect

    Pratson, L.; Malinverno, A.; Edwards, M.; Ryan, W. )

    1990-05-01

    Side-scan swath sonar systems have become an increasingly important means of mapping the sea floor. Two such systems are the deep-towed, high-resolution SeaMARC I sonar, which has a variable swath width of up to 5 km, and the shallow-towed, lower-resolution SeaMARC II sonar, which has a swath width of 10 km. The sea-floor imagery of acoustic backscatter output by the SeaMARC sonars is analogous to aerial photographs and airborne side-looking radar images of continental topography. Geologic interpretation of the sea-floor imagery is greatly facilitated by image processing. Image processing of the digital backscatter data involves removal of noise by median filtering, spatial filtering to remove sonar scans of anomalous intensity, across-track corrections to remove beam patterns caused by nonuniform response of the sonar transducers to changes in incident angle, and contrast enhancement by histogram equalization to maximize the available dynamic range. Correct geologic interpretation requires submarine structural fabrics to be displayed in their proper locations and orientations. Geographic projection of sea-floor imagery is achieved by merging the enhanced imagery with the sonar vehicle navigation and correcting for vehicle attitude. Co-registration of bathymetry with sonar imagery introduces sea-floor relief and permits the imagery to be displayed in three-dimensional perspectives, furthering the ability of the marine geologist to infer the processes shaping formerly hidden subsea terrains.

  16. Introduction to Sonar, Naval Education and Training Command. Revised Edition.

    ERIC Educational Resources Information Center

    Naval Education and Training Command, Pensacola, FL.

    This Rate Training Manual (RTM) and Nonresident Career Course form a self-study package for those U.S. Navy personnel who are seeking advancement in the Sonar Technician Rating. Among the requirements of the rating are the abilities to obtain and interpret underwater data, operate and maintain upkeep of sonar equipment, and interpret target and…

  17. Timing matters: sonar call groups facilitate target localization in bats.

    PubMed

    Kothari, Ninad B; Wohlgemuth, Melville J; Hulgard, Katrine; Surlykke, Annemarie; Moss, Cynthia F

    2014-01-01

    To successfully negotiate a cluttered environment, an echolocating bat must control the timing of motor behaviors in response to dynamic sensory information. Here we detail the big brown bat's adaptive temporal control over sonar call production for tracking prey, moving predictably or unpredictably, under different experimental conditions. We studied the adaptive control of vocal-motor behaviors in free-flying big brown bats, Eptesicus fuscus, as they captured tethered and free-flying insects, in open and cluttered environments. We also studied adaptive sonar behavior in bats trained to track moving targets from a resting position. In each of these experiments, bats adjusted the features of their calls to separate target and clutter. Under many task conditions, flying bats produced prominent sonar sound groups identified as clusters of echolocation pulses with relatively stable intervals, surrounded by longer pulse intervals. In experiments where bats tracked approaching targets from a resting position, bats also produced sonar sound groups, and the prevalence of these sonar sound groups increased when motion of the target was unpredictable. We hypothesize that sonar sound groups produced during flight, and the sonar call doublets produced by a bat tracking a target from a resting position, help the animal resolve dynamic target location and represent the echo scene in greater detail. Collectively, our data reveal adaptive temporal control over sonar call production that allows the bat to negotiate a complex and dynamic environment.

  18. Timing matters: sonar call groups facilitate target localization in bats

    PubMed Central

    Kothari, Ninad B.; Wohlgemuth, Melville J.; Hulgard, Katrine; Surlykke, Annemarie; Moss, Cynthia F.

    2014-01-01

    To successfully negotiate a cluttered environment, an echolocating bat must control the timing of motor behaviors in response to dynamic sensory information. Here we detail the big brown bat's adaptive temporal control over sonar call production for tracking prey, moving predictably or unpredictably, under different experimental conditions. We studied the adaptive control of vocal-motor behaviors in free-flying big brown bats, Eptesicus fuscus, as they captured tethered and free-flying insects, in open and cluttered environments. We also studied adaptive sonar behavior in bats trained to track moving targets from a resting position. In each of these experiments, bats adjusted the features of their calls to separate target and clutter. Under many task conditions, flying bats produced prominent sonar sound groups identified as clusters of echolocation pulses with relatively stable intervals, surrounded by longer pulse intervals. In experiments where bats tracked approaching targets from a resting position, bats also produced sonar sound groups, and the prevalence of these sonar sound groups increased when motion of the target was unpredictable. We hypothesize that sonar sound groups produced during flight, and the sonar call doublets produced by a bat tracking a target from a resting position, help the animal resolve dynamic target location and represent the echo scene in greater detail. Collectively, our data reveal adaptive temporal control over sonar call production that allows the bat to negotiate a complex and dynamic environment. PMID:24860509

  19. Miltefosine Suppresses Hepatic Steatosis by Activating AMPK Signal Pathway

    PubMed Central

    Zhu, Yaqin; Tong, Xing; Li, Kexue; Bai, Hui; Li, Xiaoyu; Ben, Jingjing; Zhang, Hanwen; Yang, Qing; Chen, Qi

    2016-01-01

    Background and Purpose It has been accepted that AMPK (Adenosine monophosphate–activated protein kinase) activation exhibits many beneficial effects on glucolipid metabolism. Lysophosphatidylcholine (LPC) is an important lysophospholipid which can improve blood glucose levels in diabetic mice and attenuate inflammation by activating AMPK signal pathway in macrophages. Synthetic alkylphospholipids (ALPs), such as miltefosine, is used as an alternate of LPC for the clinical application. Here, we investigated whether miltefosine could have an impact on hepatic steatosis and related metabolic disorders. Experimental Approach Mice were fed with high fat diet (HFD) for 16 weeks to generate an obese model. Next, the obese mice were randomly divided into three groups: saline-treated and miltefosine-treated (2.5 or 5 mg/kg/d) groups. Miltefosine was intraperitoneally administrated into mice for additional 4 weeks plus HFD treatment. Key Results It was shown that miltefosine treatment could substantially improve glucose metabolism, prevented hepatic lipid accumulation, and inhibited liver inflammation in HFD-fed mice by activating AMPK signal pathway. In vitro, miltefosine stimulated AMPKα phosphorylation both in time and dose dependent manner and decreased lipid accumulation in liver cells. When a specific AMPK inhibitor compound C was used to treat mice, the antagonistic effects of miltefosine on HFD-induced mouse hyperlipidaemia and liver steatosis were abolished. Treatment with miltefosine also dramatically inhibited the HFD-induced liver inflammation in mice. Conclusions and Implications Here we demonstrated that miltefosine might be a new activator of AMPK signal pathway in vivo and in vitro and be useful for treatment of hepatic steatosis and related metabolic disorders. PMID:27681040

  20. Cetaceans and Naval Sonar: Behavioral Response as a Function of Sonar Frequency

    DTIC Science & Technology

    2010-09-30

    labeled on the left, and the type of sonar exposure is shown by color. The dose - response curve below each histogram is the harassment dose - response curve currently...1) with indications that weighting the received levels do not improve the steepness of the dose - response curve . The results of this dose-response

  1. Glucocorticoid receptor signalling activates YAP in breast cancer

    PubMed Central

    Sorrentino, Giovanni; Ruggeri, Naomi; Zannini, Alessandro; Ingallina, Eleonora; Bertolio, Rebecca; Marotta, Carolina; Neri, Carmelo; Cappuzzello, Elisa; Forcato, Mattia; Rosato, Antonio; Mano, Miguel; Bicciato, Silvio; Del Sal, Giannino

    2017-01-01

    The Hippo pathway is an oncosuppressor signalling cascade that plays a major role in the control of cell growth, tissue homoeostasis and organ size. Dysregulation of the Hippo pathway leads to aberrant activation of the transcription co-activator YAP (Yes-associated protein) that contributes to tumorigenesis in several tissues. Here we identify glucocorticoids (GCs) as hormonal activators of YAP. Stimulation of glucocorticoid receptor (GR) leads to increase of YAP protein levels, nuclear accumulation and transcriptional activity in vitro and in vivo. Mechanistically, we find that GCs increase expression and deposition of fibronectin leading to the focal adhesion-Src pathway stimulation, cytoskeleton-dependent YAP activation and expansion of chemoresistant cancer stem cells. GR activation correlates with YAP activity in human breast cancer and predicts bad prognosis in the basal-like subtype. Our results unveil a novel mechanism of YAP activation in cancer and open the possibility to target GR to prevent cancer stem cells self-renewal and chemoresistance. PMID:28102225

  2. Signal integration by Ca2+ regulates intestinal stem cell activity

    PubMed Central

    Deng, Hansong; Gerencser, Akos A.; Jasper, Heinrich

    2015-01-01

    Summary Somatic stem cells (SCs) maintain tissue homeostasis by dynamically adjusting proliferation and differentiation in response to stress and metabolic cues. Here, we identify Ca2+ signaling as a central regulator of intestinal SC (ISC) activity in Drosophila. We find that dietary L-glutamate stimulates ISC division and gut growth. The metabotropic glutamate receptor (mGluR) is required in ISCs for this response and for an associated modulation of cytosolic Ca2+ oscillations that results in sustained high cytosolic Ca2+ concentrations. High cytosolic Ca2+ induces ISC proliferation by regulating Calcineurin and CREB - regulated transcriptional co-activator (CRTC). In response to a wide range of dietary and stress stimuli, ISCs reversibly transition between Ca2+ oscillation states that represent poised or activated modes of proliferation, respectively. We propose that the dynamic regulation of intracellular Ca2+ levels allows effective integration of diverse mitogenic signals in ISCs to tailor their proliferative activity to the needs of the tissue. PMID:26633624

  3. Robust Indoor Human Activity Recognition Using Wireless Signals

    PubMed Central

    Wang, Yi; Jiang, Xinli; Cao, Rongyu; Wang, Xiyang

    2015-01-01

    Wireless signals–based activity detection and recognition technology may be complementary to the existing vision-based methods, especially under the circumstance of occlusions, viewpoint change, complex background, lighting condition change, and so on. This paper explores the properties of the channel state information (CSI) of Wi-Fi signals, and presents a robust indoor daily human activity recognition framework with only one pair of transmission points (TP) and access points (AP). First of all, some indoor human actions are selected as primitive actions forming a training set. Then, an online filtering method is designed to make actions’ CSI curves smooth and allow them to contain enough pattern information. Each primitive action pattern can be segmented from the outliers of its multi-input multi-output (MIMO) signals by a proposed segmentation method. Lastly, in online activities recognition, by selecting proper features and Support Vector Machine (SVM) based multi-classification, activities constituted by primitive actions can be recognized insensitive to the locations, orientations, and speeds. PMID:26184231

  4. Pathway connectivity and signaling coordination in the yeast stress-activated signaling network

    PubMed Central

    Chasman, Deborah; Ho, Yi-Hsuan; Berry, David B; Nemec, Corey M; MacGilvray, Matthew E; Hose, James; Merrill, Anna E; Lee, M Violet; Will, Jessica L; Coon, Joshua J; Ansari, Aseem Z; Craven, Mark; Gasch, Audrey P

    2014-01-01

    Stressed cells coordinate a multi-faceted response spanning many levels of physiology. Yet knowledge of the complete stress-activated regulatory network as well as design principles for signal integration remains incomplete. We developed an experimental and computational approach to integrate available protein interaction data with gene fitness contributions, mutant transcriptome profiles, and phospho-proteome changes in cells responding to salt stress, to infer the salt-responsive signaling network in yeast. The inferred subnetwork presented many novel predictions by implicating new regulators, uncovering unrecognized crosstalk between known pathways, and pointing to previously unknown ‘hubs’ of signal integration. We exploited these predictions to show that Cdc14 phosphatase is a central hub in the network and that modification of RNA polymerase II coordinates induction of stress-defense genes with reduction of growth-related transcripts. We find that the orthologous human network is enriched for cancer-causing genes, underscoring the importance of the subnetwork's predictions in understanding stress biology. PMID:25411400

  5. Enhanced echolocation via robust statistics and super-resolution of sonar images

    NASA Astrophysics Data System (ADS)

    Kim, Kio

    Echolocation is a process in which an animal uses acoustic signals to exchange information with environments. In a recent study, Neretti et al. have shown that the use of robust statistics can significantly improve the resiliency of echolocation against noise and enhance its accuracy by suppressing the development of sidelobes in the processing of an echo signal. In this research, the use of robust statistics is extended to problems in underwater explorations. The dissertation consists of two parts. Part I describes how robust statistics can enhance the identification of target objects, which in this case are cylindrical containers filled with four different liquids. Particularly, this work employs a variation of an existing robust estimator called an L-estimator, which was first suggested by Koenker and Bassett. As pointed out by Au et al.; a 'highlight interval' is an important feature, and it is closely related with many other important features that are known to be crucial for dolphin echolocation. A varied L-estimator described in this text is used to enhance the detection of highlight intervals, which eventually leads to a successful classification of echo signals. Part II extends the problem into 2 dimensions. Thanks to the advances in material and computer technology, various sonar imaging modalities are available on the market. By registering acoustic images from such video sequences, one can extract more information on the region of interest. Computer vision and image processing allowed application of robust statistics to the acoustic images produced by forward looking sonar systems, such as Dual-frequency Identification Sonar and ProViewer. The first use of robust statistics for sonar image enhancement in this text is in image registration. Random Sampling Consensus (RANSAC) is widely used for image registration. The registration algorithm using RANSAC is optimized for sonar image registration, and the performance is studied. The second use of robust

  6. Spawning behaviour of Allis shad Alosa alosa: new insights based on imaging sonar data.

    PubMed

    Langkau, M C; Clavé, D; Schmidt, M B; Borcherding, J

    2016-06-01

    Spawning behaviour of Alosa alosa was observed by high resolution imaging sonar. Detected clouds of sexual products and micro bubbles served as a potential indicator of spawning activity. Peak spawning time was between 0130 and 0200 hours at night. Increasing detections over three consecutive nights were consistent with sounds of mating events (bulls) assessed in hearing surveys in parallel to the hydro acoustic detection. In 70% of the analysed mating events there were no additional A. alosa joining the event whilst 70% of the mating events showed one or two A. alosa leaving the cloud. In 31% of the analysed mating events, however, three or more A. alosa were leaving the clouds, indicating that matings are not restricted to a pair. Imaging sonar is suitable for monitoring spawning activity and behaviour of anadromous clupeids in their spawning habitats.

  7. Mitogen Activated Protein kinase signal transduction pathways in the prostate

    PubMed Central

    Maroni, Paul D; Koul, Sweaty; Meacham, Randall B; Koul, Hari K

    2004-01-01

    The biochemistry of the mitogen activated protein kinases ERK, JNK, and p38 have been studied in prostate physiology in an attempt to elucidate novel mechanisms and pathways for the treatment of prostatic disease. We reviewed articles examining mitogen-activated protein kinases using prostate tissue or cell lines. As with other tissue types, these signaling modules are links/transmitters for important pathways in prostate cells that can result in cellular survival or apoptosis. While the activation of the ERK pathway appears to primarily result in survival, the roles of JNK and p38 are less clear. Manipulation of these pathways could have important implications for the treatment of prostate cancer and benign prostatic hypertrophy. PMID:15219238

  8. Visualizing how T cells collect activation signals in vivo.

    PubMed

    Moreau, Hélène D; Bousso, Philippe

    2014-02-01

    A decade ago the first movies depicting T cell behavior in vivo with the help of two-photon microscopy were generated. These initial experiments revealed that T cells migrate rapidly and randomly in secondary lymphoid organs at steady state and profoundly alter their behavior during antigen recognition, establishing both transient and stable contacts with antigen-presenting cells (APCs). Since then, in vivo imaging has continuously improved our understanding of T cell activation. In particular, recent studies uncovered how T cells may be guided in their search for the best APCs. Additionally, the development of more sophisticated fluorescent tools has permitted not only to visualize T cell-APC contacts but also to probe their functional impact on T cell activation. These recent progresses are providing new insights into how T cells sense antigen, collect activation signals during distinct types of interaction and integrate information over successive encounters.

  9. Nucleophosmin leukemogenic mutant activates Wnt signaling during zebrafish development

    PubMed Central

    Barbieri, Elisa; Deflorian, Gianluca; Pezzimenti, Federica; Valli, Debora; Saia, Marco; Meani, Natalia

    2016-01-01

    Nucleophosmin (NPM1) is a ubiquitous multifunctional phosphoprotein with both oncogenic and tumor suppressor functions. Mutations of the NPM1 gene are the most frequent genetic alterations in acute myeloid leukemia (AML) and result in the expression of a mutant protein with aberrant cytoplasmic localization, NPMc+. Although NPMc+ causes myeloproliferation and AML in animal models, its mechanism of action remains largely unknown. Here we report that NPMc+ activates canonical Wnt signaling during the early phases of zebrafish development and determines a Wnt-dependent increase in the number of progenitor cells during primitive hematopoiesis. Coherently, the canonical Wnt pathway is active in AML blasts bearing NPMc+ and depletion of the mutant protein in the patient derived OCI-AML3 cell line leads to a decrease in the levels of active β-catenin and of Wnt target genes. Our results reveal a novel function of NPMc+ and provide insight into the molecular pathogenesis of AML bearing NPM1 mutations. PMID:27486814

  10. p21-activated kinase signaling in breast cancer

    PubMed Central

    Gururaj, Anupama E; Rayala, Suresh K; Kumar, Rakesh

    2005-01-01

    The p21-activated kinases signal through a number of cellular pathways fundamental to growth, differentiation and apoptosis. A wealth of information has accumulated at an impressive pace in the recent past, both with regard to previously identified targets for p21-activated kinases that regulate the actin cytoskeleton and cellular stress pathways and with regard to newly identified targets and their role in cancer. Emerging data also provide new clues towards a previously unappreciated link between these various cellular processes. The present review attempts to provide a quick tutorial to the reader about the evolving significance of p21-activated kinases and small GTPases in breast cancer, using information from mouse models, tissue culture studies, and human materials. PMID:15642175

  11. Digital signaling and hysteresis characterize Ras activation in lymphoid cells

    PubMed Central

    Das, Jayajit; Ho, Mary; Zikherman, Julie; Govern, Christopher; Yang, Ming; Weiss, Arthur; Chakraborty, Arup K.; Roose, Jeroen P.

    2009-01-01

    Activation of Ras proteins underlies functional decisions in diverse cell types. Two molecules, RasGRP and SOS, catalyze Ras activation in lymphocytes. Binding of active Ras to SOS′ allosteric pocket markedly increases SOS′ activity establishing a positive feedback loop for SOS-mediated Ras activation. Integrating in silico and in vitro studies, we demonstrate that digital signaling in lymphocytes (cells are “on” or “off”) is predicated upon feedback regulation of SOS. SOS′ feedback loop leads to hysteresis in the dose-response curve, which can enable a capacity to sustain Ras activation as stimuli are withdrawn and exhibit “memory” of past encounters with antigen. Ras activation via RasGRP alone is analog (graded increase in amplitude with stimulus). We describe how complementary analog (RasGRP) and digital (SOS) pathways act on Ras to efficiently convert analog input to digital output. Numerous predictions regarding the impact of our findings on lymphocyte function and development are noted. PMID:19167334

  12. Mechanical charactization of sonar window materials

    SciTech Connect

    DeTeresa, S.J.; Groves, S.E.; Harwood, P.J.; Sanchez, R.J.

    1996-03-25

    The three-dimensional mechanical behavior of thick Spectra/epoxy sonar window materials containing various special materials is summarized in this report. Three different materials, which were fabricated by two companies known as `A` and `B` were received from the Naval Warfare Center. The three materials designated `A with microspheres (A micron),` `A without microspheres (A),` and `B` were measured for all properties. The total number of tests was reduced through the assumption that the two orthogonal, in-place directions were identical. Consequently, these materials should have only six independent elastic variables. The measured constants and strengths are given.

  13. Sonar Transducer Reliability Improvement Program FY 80

    DTIC Science & Technology

    1980-10-01

    Polyphenylene Sulfide 15,320 23,000 Nylon 6/10 14,070 26,000 High-Strength Nylon (ZYTEL) 11,270 24,000 Amorphous Nylon 14,139 25,000 PBT Polyester...transducer receiving sensitivity Goal -- less than ±1 dB variation from the specified value over operational frequency band . Threshold - less than ±2 dB...variation from the specified value over operational feequency band . rhe Sonar Transducer Reliability Impruvemen: Program (STRIP) is a part of Program

  14. Sonar Test and Test Instrumentation Support.

    DTIC Science & Technology

    1979-03-29

    CONTRACT OR GRANT NUMBER(s) Nool40-76-c-6487 Dudley D. Baker et al. S. PERFORMING ORGANIZATION NAME AND ADDRESS 10 . PROGRAM ELEMENT. PROJECT, TASK AREA...Date Entered) TABLE OF CONTENTS Page I. INTRODUCTION 1 II. TRF, AN/FQM- 10 (V), AND AN/WQM-5 FIELD SUPPORT 3 A. Pressure Vessel Stuffing Tubes 3 B. AN/FQM...Test Set 9 * , D. SACS Support 10 1. Hardware Documentation 10 2. Software Documentation 10 3. Sonar Controller Installation 10 4. AN/SQS-35/38 Study 11

  15. Detecting Atlantic herring by parametric sonar.

    PubMed

    Godo, Olav Rune; Foote, Kenneth G; Dybedal, Johnny; Tenningen, Eirik; Patel, Ruben

    2010-04-01

    The difference-frequency band of the Kongsberg TOPAS PS18 parametric sub-bottom profiling sonar, nominally 1-6 kHz, is being used to observe Atlantic herring. Representative TOPAS echograms of herring layers and schools observed in situ in December 2008 and November 2009 are presented. These agree well with echograms of volume backscattering strength derived simultaneously with the narrowband Simrad EK60/18- and 38-kHz scientific echo sounder, also giving insight into herring avoidance behavior in relation to survey vessel passage. Progress in rendering the TOPAS echograms quantitative is described.

  16. Tribotronic Tuning Diode for Active Analog Signal Modulation.

    PubMed

    Zhou, Tao; Yang, Zhi Wei; Pang, Yaokun; Xu, Liang; Zhang, Chi; Wang, Zhong Lin

    2017-01-24

    Realizing active interaction with external environment/stimuli is a great challenge for current electronics. In this paper, a tribotronic tuning diode (TTD) is proposed by coupling a variable capacitance diode and a triboelectric nanogenerator in free-standing sliding mode. When the friction layer is sliding on the device surface for electrification, a reverse bias voltage is created and applied to the diode for tuning the junction capacitance. When the sliding distance increases from 0 to 25 mm, the capacitance of the TTD decreases from about 39 to 8 pF. The proposed TTD has been integrated into analog circuits and exhibited excellent performances in frequency modulation, phase shift, and filtering by sliding a finger. This work has demonstrated tunable diode and active analog signal modulation by tribotronics, which has great potential to replace ordinary variable capacitance diodes in various practical applications such as signal processing, electronic tuning circuits, precise tuning circuits, active sensor networks, electronic communications, remote controls, flexible electronics, etc.

  17. Dolphin and bat sonar: Convergence, divergence, or parallelism

    NASA Astrophysics Data System (ADS)

    Ketten, Darlene R.; Simmons, James; Hubbard, Allyn E.; Mountain, David A.

    2001-05-01

    During the explosive period of mammalian radiation, two groups emerged with highly effective biosonar systems, bats and toothed whales. In the intervening 50 million years, these groups evolutionarily honed their hearing for operation in radically different media. This paper addresses what functional aspects the media influenced in the biosonar receptors of bats versus dolphins by comparing the auditory peripheries of these groups. Data were obtained using thin-section microscopy, CT imaging, and inner-ear models. Inner-ear anatomy is fundamentally similar in these animals, although differences exist in both neural density and distribution in each group. Specialist ears are present in both groups, suggesting at least one odontocete species has cochlear specializations consistent with CF-FM bats, including specialized basilar-membrane regions and high-frequency neural foveal areas. Cochlear specializations in both groups are primarily linked to peak spectra of sonar signals, may expand frequency representation, and may enhance tuning in adjacent ear segments by generating standing wave phenomena. Most differences, such as the soft-tissue external ear analogs in odontocetes, are clearly media driven. Other differences among species within each group are correlated with signal type or habitat complexity. [Work supported by Mellon Foundation; Seaver Institute; ONR.

  18. Bi-static sonar applications of intensity processing.

    PubMed

    Naluai, Nathan K; Lauchle, Gerald C; Gabrielson, Thomas B; Joseph, John H

    2007-04-01

    Acoustic intensity processing of signals from directional sonobuoy acoustic subsystems is used to enhance the detection of submerged bodies in bi-static sonar applications. In some directions, the scattered signals may be completely dominated by the incident blast from the source, depending upon the geometry, making the object undetectable by traditional pressure measurements. Previous theoretical derivations suggest that acoustic vector intensity sensors, and the associated intensity processing, are a potential solution to this problem. Deep water experiments conducted at Lake Pend Oreille in northern Idaho are described. A large, hollow cylindrical body is located between a source and a number of SSQ-53D sonobuoys positioned from 5 to 30 body lengths away from the scattering body. Measurements show changes in the acoustic pressure of less than 0.5 dB when the scattering body is inserted in the field. However, the phase of the acoustic intensity component formed between the acoustic pressure and particle velocity component orthogonal to the direction of incident wave propagation varies by as much as 55 degrees. This metric is shown to be a repeatable and strong indicator of the presence of the scattering body.

  19. Dolphin and bat sonar: Convergence, divergence, or parallelism

    NASA Astrophysics Data System (ADS)

    Ketten, Darlene R.; Simmons, James; Hubbard, Allyn E.; Mountain, David A.

    2004-05-01

    During the explosive period of mammalian radiation, two groups emerged with highly effective biosonar systems, bats and toothed whales. In the intervening 50 million years, these groups evolutionarily honed their hearing for operation in radically different media. This paper addresses what functional aspects the media influenced in the biosonar receptors of bats versus dolphins by comparing the auditory peripheries of these groups. Data were obtained using thin-section microscopy, CT imaging, and inner-ear models. Inner-ear anatomy is fundamentally similar in these animals, although differences exist in both neural density and distribution in each group. Specialist ears are present in both groups, suggesting at least one odontocete species has cochlear specializations consistent with CF-FM bats, including specialized basilar-membrane regions and high-frequency neural foveal areas. Cochlear specializations in both groups are primarily linked to peak spectra of sonar signals, may expand frequency representation, and may enhance tuning in adjacent ear segments by generating standing wave phenomena. Most differences, such as the soft-tissue external ear analogs in odontocetes, are clearly media driven. Other differences among species within each group are correlated with signal type or habitat complexity. [Work supported by Mellon Foundation; Seaver Institute; ONR.

  20. Location and Characterization of Underwater Ordnance using Resonance Scattered Sonar

    NASA Astrophysics Data System (ADS)

    Gritto, R.; Korneev, V. A.

    2009-12-01

    Unexploded ordnance (UXO) present a worldwide hazard in locations of previous military confrontations and at military training facilities. In particular, the presence of unexploded ordinance in coastal regions poses a severe risk that must be addressed before sites can be turned over to the public or coastal areas made available for commercial traffic. Although progress has been made in detecting UXO in underwater areas, there still exists a need for technologies that can detect and locate UXO buried in seafloor sediments and reliably distinguish munitions from clutter. We are investigating a method based on resonance scattering using small data sets in a controlled pond environment. The use of resonance scattering allows for deeper bottom penetration than in the case of the generally used acoustic imaging, because in the former case the wavelengths are longer than the latter. Furthermore, in the resonance scattering regime the geometry is independent of the target orientation. The sonar data sets were acquired during 2006 and 2007 by the Applied Physics Laboratory, University of Washington, at the Surface Warfare Center, Panama City, FL, and included an aluminum cylinder and sphere, as well as artillery shells and mortar rounds buried in the sandy pond bottom. Our results show that resonance scattered waves, although smaller in amplitude than the specular reflected signal, dominate much of the recorded traces in time. These signals can be used to determine the propagation velocities in the pond sediments, to locate the UXO in the subsurface and to characterize the UXO type by its size and filler velocities.

  1. 50 CFR 216.170 - Specified activity and specified geographical region.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...-frequency active sonar (MFAS) and high frequency active sonar (HFAS) sources for U.S. Navy anti-submarine... torpedoes per year) (vi) AN/BQQ-10 (submarine mounted sonar)—up to 1000 hours over the course of 5 years...

  2. Sonar beam dynamics in leaf-nosed bats.

    PubMed

    Linnenschmidt, Meike; Wiegrebe, Lutz

    2016-07-07

    Ultrasonic emissions of bats are directional and delimit the echo-acoustic space. Directionality is quantified by the aperture of the sonar beam. Recent work has shown that bats often widen their sonar beam when approaching movable prey or sharpen their sonar beam when navigating through cluttered habitats. Here we report how nose-emitting bats, Phyllostomus discolor, adjust their sonar beam to object distance. First, we show that the height and width of the bats sonar beam, as imprinted on a parabolic 45 channel microphone array, varies even within each animal and this variation is unrelated to changes in call level or spectral content. Second, we show that these animals are able to systematically decrease height and width of their sonar beam while focusing on the approaching object. Thus it appears that sonar beam sharpening is a further, facultative means of reducing search volume, likely to be employed by stationary animals when the object position is close and unambiguous. As only half of our individuals sharpened their beam onto the approaching object we suggest that this strategy is facultative, under voluntary control, and that beam formation is likely mediated by muscular control of the acoustic aperture of the bats' nose leaf.

  3. Sonar beam dynamics in leaf-nosed bats

    PubMed Central

    Linnenschmidt, Meike; Wiegrebe, Lutz

    2016-01-01

    Ultrasonic emissions of bats are directional and delimit the echo-acoustic space. Directionality is quantified by the aperture of the sonar beam. Recent work has shown that bats often widen their sonar beam when approaching movable prey or sharpen their sonar beam when navigating through cluttered habitats. Here we report how nose-emitting bats, Phyllostomus discolor, adjust their sonar beam to object distance. First, we show that the height and width of the bats sonar beam, as imprinted on a parabolic 45 channel microphone array, varies even within each animal and this variation is unrelated to changes in call level or spectral content. Second, we show that these animals are able to systematically decrease height and width of their sonar beam while focusing on the approaching object. Thus it appears that sonar beam sharpening is a further, facultative means of reducing search volume, likely to be employed by stationary animals when the object position is close and unambiguous. As only half of our individuals sharpened their beam onto the approaching object we suggest that this strategy is facultative, under voluntary control, and that beam formation is likely mediated by muscular control of the acoustic aperture of the bats’ nose leaf. PMID:27384865

  4. Dose-response relationships for the onset of avoidance of sonar by free-ranging killer whales.

    PubMed

    Miller, Patrick J O; Antunes, Ricardo N; Wensveen, Paul J; Samarra, Filipa I P; Alves, Ana Catarina; Tyack, Peter L; Kvadsheim, Petter H; Kleivane, Lars; Lam, Frans-Peter A; Ainslie, Michael A; Thomas, Len

    2014-02-01

    Eight experimentally controlled exposures to 1-2 kHz or 6-7 kHz sonar signals were conducted with four killer whale groups. The source level and proximity of the source were increased during each exposure in order to reveal response thresholds. Detailed inspection of movements during each exposure session revealed sustained changes in speed and travel direction judged to be avoidance responses during six of eight sessions. Following methods developed for Phase-I clinical trials in human medicine, response thresholds ranging from 94 to 164 dB re 1 μPa received sound pressure level (SPL) were fitted to Bayesian dose-response functions. Thresholds did not consistently differ by sonar frequency or whether a group had previously been exposed, with a mean SPL response threshold of 142 ± 15 dB (mean ± s.d.). High levels of between- and within-individual variability were identified, indicating that thresholds depended upon other undefined contextual variables. The dose-response functions indicate that some killer whales started to avoid sonar at received SPL below thresholds assumed by the U.S. Navy. The predicted extent of habitat over which avoidance reactions occur depends upon whether whales responded to proximity or received SPL of the sonar or both, but was large enough to raise concerns about biological consequences to the whales.

  5. Activated platelets signal chemokine synthesis by human monocytes.

    PubMed Central

    Weyrich, A S; Elstad, M R; McEver, R P; McIntyre, T M; Moore, K L; Morrissey, J H; Prescott, S M; Zimmerman, G A

    1996-01-01

    Human blood monocytes adhere rapidly and for prolonged periods to activated platelets that display P-selectin, an adhesion protein that recognizes a specific ligand on leukocytes, P-selectin glycoprotein-1. We previously demonstrated that P-selectin regulates expression and secretion of cytokines by stimulated monocytes when it is presented in a purified, immobilized form or by transfected cells. Here we show that thrombin-activated platelets induce the expression and secretion of monocyte chemotactic protein-1 and IL-8 by monocytes. Enhanced monokine synthesis requires engagement of P-selectin glycoprotein-1 on the leukocyte by P-selectin on the platelet. Secretion of the chemokines is not, however, directly signaled by P-selectin; instead, tethering of the monocytes by P-selectin is required for their activation by RANTES (regulated upon activation normal T cell expressed presumed secreted), a platelet chemokine not previously known to induce immediate-early gene products in monocytes. Adhesion of monocytes to activated platelets results in nuclear translocation of p65 (RelA), a component of the NF-kappaB family of transcription factors that binds kappaB sequences in the regulatory regions of monocyte chemotactic protein-1, IL-8, and other immediate-early genes. However, expression of tissue factor, a coagulation protein that also has a kappaB sequence in the 5' regulatory region of its gene, is not induced in monocytes adherent to activated platelets. Thus, contact of monocytes with activated platelets differentially affects the expression of monocyte products. These experiments suggest that activated platelets regulate chemokine secretion by monocytes in inflammatory lesions in vivo and provide a model for the study of gene regulation in cell-cell interactions. PMID:8617886

  6. Psoralen stimulates osteoblast differentiation through activation of BMP signaling.

    PubMed

    Tang, De-Zhi; Yang, Feng; Yang, Zhou; Huang, Jian; Shi, Qi; Chen, Di; Wang, Yong-Jun

    2011-02-11

    Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. In order to improve the treatment of osteoporosis, identification of anabolic and orally available agents with minimal side effects is highly desirable. Psoralen is a coumarin-like derivative extracted from Chinese herbs, which have been used to treat bone diseases for thousands of years. However, the role of Psoralen in osteoblast function and the underlying molecular mechanisms remain poorly understood. In this study, we found that Psoralen promoted osteoblast differentiation in primary mouse calvarial osteoblasts in a dose-dependent manner, demonstrated by up-regulation of expressions of osteoblast-specific marker genes including type I collagen, osteocalcin and bone sialoprotein and enhancement of alkaline phosphatase activity. We further demonstrated that Psoralen up-regulated the expression of Bmp2 and Bmp4 genes, increased the protein level of phospho-Smad1/5/8, and activated BMP reporter (12xSBE-OC-Luc) activity in a dose-dependent manner, as well as enhanced the expression of Osx, the direct target gene of BMP signaling. Deletion of the Bmp2 and Bmp4 genes abolished the stimulatory effect of Psoralen on the expression of osteoblast marker genes, such as Col1, Alp, Oc and Bsp. Our results suggest that Psoralen acts through the activation of BMP signaling to promote osteoblast differentiation and demonstrate that Psoralen could be a potential anabolic agent to treat patients with bone loss-associated diseases such as osteoporosis.

  7. Dynamic neural activity during stress signals resilient coping

    PubMed Central

    Sinha, Rajita; Lacadie, Cheryl M.; Constable, R. Todd; Seo, Dongju

    2016-01-01

    Active coping underlies a healthy stress response, but neural processes supporting such resilient coping are not well-known. Using a brief, sustained exposure paradigm contrasting highly stressful, threatening, and violent stimuli versus nonaversive neutral visual stimuli in a functional magnetic resonance imaging (fMRI) study, we show significant subjective, physiologic, and endocrine increases and temporally related dynamically distinct patterns of neural activation in brain circuits underlying the stress response. First, stress-specific sustained increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right dorsolateral prefrontal cortex (DLPFC) regions supported the stress processing and reactivity circuit. Second, dynamic neural activation during stress versus neutral runs, showing early increases followed by later reduced activation in the ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), left DLPFC, hippocampus, and left insula, suggested a stress adaptation response network. Finally, dynamic stress-specific mobilization of the ventromedial prefrontal cortex (VmPFC), marked by initial hypoactivity followed by increased VmPFC activation, pointed to the VmPFC as a key locus of the emotional and behavioral control network. Consistent with this finding, greater neural flexibility signals in the VmPFC during stress correlated with active coping ratings whereas lower dynamic activity in the VmPFC also predicted a higher level of maladaptive coping behaviors in real life, including binge alcohol intake, emotional eating, and frequency of arguments and fights. These findings demonstrate acute functional neuroplasticity during stress, with distinct and separable brain networks that underlie critical components of the stress response, and a specific role for VmPFC neuroflexibility in stress-resilient coping. PMID:27432990

  8. Optimal Predator Risk Assessment by the Sonar-Jamming Arctiine Moth Bertholdia trigona

    PubMed Central

    Corcoran, Aaron J.; Wagner, Ryan D.; Conner, William E.

    2013-01-01

    Nearly all animals face a tradeoff between seeking food and mates and avoiding predation. Optimal escape theory holds that an animal confronted with a predator should only flee when benefits of flight (increased survival) outweigh the costs (energetic costs, lost foraging time, etc.). We propose a model for prey risk assessment based on the predator's stage of attack. Risk level should increase rapidly from when the predator detects the prey to when it commits to the attack. We tested this hypothesis using a predator – the echolocating bat – whose active biosonar reveals its stage of attack. We used a prey defense – clicking used for sonar jamming by the tiger moth Bertholdia trigona– that can be readily studied in the field and laboratory and is enacted simultaneously with evasive flight. We predicted that prey employ defenses soon after being detected and targeted, and that prey defensive thresholds discriminate between legitimate predatory threats and false threats where a nearby prey is attacked. Laboratory and field experiments using playbacks of ultrasound signals and naturally behaving bats, respectively, confirmed our predictions. Moths clicked soon after bats detected and targeted them. Also, B. trigona clicking thresholds closely matched predicted optimal thresholds for discriminating legitimate and false predator threats for bats using search and approach phase echolocation – the period when bats are searching for and assessing prey. To our knowledge, this is the first quantitative study to correlate the sensory stimuli that trigger defensive behaviors with measurements of signals provided by predators during natural attacks in the field. We propose theoretical models for explaining prey risk assessment depending on the availability of cues that reveal a predator's stage of attack. PMID:23671686

  9. Sonar target enhancement by shrinkage of incoherent wavelet coefficients.

    PubMed

    Hunter, Alan J; van Vossen, Robbert

    2014-01-01

    Background reverberation can obscure useful features of the target echo response in broadband low-frequency sonar images, adversely affecting detection and classification performance. This paper describes a resolution and phase-preserving means of separating the target response from the background reverberation noise using a coherence-based wavelet shrinkage method proposed recently for de-noising magnetic resonance images. The algorithm weights the image wavelet coefficients in proportion to their coherence between different looks under the assumption that the target response is more coherent than the background. The algorithm is demonstrated successfully on experimental synthetic aperture sonar data from a broadband low-frequency sonar developed for buried object detection.

  10. Signal-to-noise ratio in neuro activation PET studies

    SciTech Connect

    Votaw, J.R.

    1996-04-01

    It has become commonplace to compare scanner sensitivity characteristics by comparing noise equivalent count rate curves. However, because a 20-cm diameter uniform phantom is drastically difference from a human brain, these curves give misleading information when planning a neuro activation PET experiment. Signal-to-noise ratio (SNR) calculations have been performed using measured data (Siemens 921 scanner) from the three-dimensional (3-D) Hoffman brain phantom for the purpose of determining the optimal injection and scanning protocol for [{sup 15}O] labeled activation experiments. Region of interest (ROI) values along with the variance due to prompt (trues plus randoms) and random events were determined for various regions and radioactivity concentrations. Calculated attenuation correction was used throughout. Scatter correction was not used when calculating the SNR in activation studies because the number of scattered events is almost identical in each data acquisition and hence cancels. The results indicate that randoms correction should not be performed and that rather than being limited by the scanner capabilities, neuro activation experiments are limited by the amount of radioactivity that can be injected and the length of time the patient can stay in the scanner.

  11. Accelerated Lactate Dehydrogenase Activity Potentiates Osteoclastogenesis via NFATc1 Signaling

    PubMed Central

    Kim, Jin Man; Kwon, So Hyun; Lee, Seoung Hoon; Lee, Soo Young; Jeong, Daewon

    2016-01-01

    Osteoclasts seem to be metabolic active during their differentiation and bone-resorptive activation. However, the functional role of lactate dehydrogenase (LDH), a tetrameric enzyme consisting of an A and/or B subunit that catalyzes interconversion of pyruvate to lactate, in RANKL-induced osteoclast differentiation is not known. In this study, RANKL treatment induced gradual gene expression and activation of the LDH A2B2 isotype during osteoclast differentiation as well as the LDH A1B3 and B4 isotypes during osteoclast maturation after pre-osteoclast formation. Glucose consumption and lactate production in growth media were accelerated during osteoclast differentiation, together with enhanced expression of H+-lactate co-transporter and increased extracellular acidification, demonstrating that glycolytic metabolism was stimulated during differentiation. Further, oxygen consumption via mitochondria was stimulated during osteoclast differentiation. On the contrary, depletion of LDH-A or LDH-B subunit suppressed both glycolytic and mitochondrial metabolism, resulting in reduced mature osteoclast formation via decreased osteoclast precursor fusion and down-regulation of the osteoclastogenic critical transcription factor NFATc1 and its target genes. Collectively, our findings suggest that RANKL-induced LDH activation stimulates glycolytic and mitochondrial respiratory metabolism, facilitating mature osteoclast formation via osteoclast precursor fusion and NFATc1 signaling. PMID:27077737

  12. Cetaceans and Naval Sonar: Behavioral Response as a Function of Sonar Frequency

    DTIC Science & Technology

    2009-09-30

    initially motivated by observations of possible killer whale (Orcinus orca) reactions to sonars, in the Vestfjord basin of Norway and the USS Shoup...that works with killer whales . The high public profile of killer whales and the overlap of their habitats with operational areas make it likely...that incidents will continue to occur worldwide. The killer whale population involved in the USS Shoup incident has been listed as endangered under the

  13. Betulin inhibits lung carcinoma proliferation through activation of AMPK signaling.

    PubMed

    Li, Xian-Dong; Zhang, Yi-Jie; Han, Ji-Chang

    2014-11-01

    Betulin (lup-20(29)-ene-3β, 28-diol) is an abundant, naturally occurring triterpene. It is commonly isolated from the bark of birch trees and forms up to 30% of the dry weight of the extractive. In the present study, we revealed its antiproliferative effects and mechanisms using two lung carcinoma cells (A549 and NCI-292). By 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and bromodeoxyuridine (BrdU) incorporation assays, we found that betulin could efficiently inhibit cell growth and proliferation. Besides, several key genes of cell-cycle regulators were also affected by betulin treatment. At the molecular level, our results demonstrated that treatment with betulin was also associated with activation of AMP kinase and inhibition of mTOR/p70S6K/pS6 signaling in these cells. In agreement, inhibition of AMPK signaling largely reversed the antiproliferative roles of betulin. Taken together, these data provide evidence for a mechanism that may contribute to the antineoplastic effects of betulin and justify further work to explore its potential roles in lung cancer prevention and treatment.

  14. Innate Immune Signaling Activated by MDR Bacteria in the Airway.

    PubMed

    Parker, Dane; Ahn, Danielle; Cohen, Taylor; Prince, Alice

    2016-01-01

    Health care-associated bacterial pneumonias due to multiple-drug resistant (MDR) pathogens are an important public health problem and are major causes of morbidity and mortality worldwide. In addition to antimicrobial resistance, these organisms have adapted to the milieu of the human airway and have acquired resistance to the innate immune clearance mechanisms that normally prevent pneumonia. Given the limited efficacy of antibiotics, bacterial clearance from the airway requires an effective immune response. Understanding how specific airway pathogens initiate and regulate innate immune signaling, and whether this response is excessive, leading to host-induced pathology may guide future immunomodulatory therapy. We will focus on three of the most important causes of health care-associated pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, and review the mechanisms through which an inappropriate or damaging innate immune response is stimulated, as well as describe how airway pathogens cause persistent infection by evading immune activation.

  15. Innate Immune Signaling Activated by MDR Bacteria in the Airway

    PubMed Central

    Parker, Dane; Ahn, Danielle; Cohen, Taylor; Prince, Alice

    2015-01-01

    Health care-associated bacterial pneumonias due to multiple-drug resistant (MDR) pathogens are an important public health problem and are major causes of morbidity and mortality worldwide. In addition to antimicrobial resistance, these organisms have adapted to the milieu of the human airway and have acquired resistance to the innate immune clearance mechanisms that normally prevent pneumonia. Given the limited efficacy of antibiotics, bacterial clearance from the airway requires an effective immune response. Understanding how specific airway pathogens initiate and regulate innate immune signaling, and whether this response is excessive, leading to host-induced pathology may guide future immunomodulatory therapy. We will focus on three of the most important causes of health care-associated pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, and review the mechanisms through which an inappropriate or damaging innate immune response is stimulated, as well as describe how airway pathogens cause persistent infection by evading immune activation. PMID:26582515

  16. Signaling pathways regulating cartilage growth plate formation and activity.

    PubMed

    Samsa, William E; Zhou, Xin; Zhou, Guang

    2017-02-01

    The growth plate is a highly specialized and dynamic cartilage structure that serves many essential functions in skeleton patterning, growth and endochondral ossification in developing vertebrates. Major signaling pathways initiated by classical morphogens and by other systemic and tissue-specific factors are intimately involved in key aspects of growth plate development. As a corollary of these essential functions, disturbances in these pathways due to mutations or environmental factors lead to severe skeleton disorders. Here, we review these pathways and the most recent progress made in understanding their roles in chondrocyte differentiation in growth plate development and activity. Furthermore, we discuss newly uncovered pathways involved in growth plate formation, including mTOR, the circadian clock, and the COP9 signalosome.

  17. A Mobile Robot Sonar System with Obstacle Avoidance.

    DTIC Science & Technology

    1994-03-01

    vehicle, robot, obstacle avoidance, sonar sensing 102 17. SECURITY CLASSWIFCATION 1S. SECURITY CLASINFICATION I& SECURITY CLASSIFICATION 20. UMITATION...WITH OBSTACLE - AVOIDANCE __ by __ Patrick Gerard Byrne March 1994 Thesis Advisor: Yutaka Kanayama Approved for public release; distribution is...SEOLY(Lae anO r Iff TDT, Master’s Thesis _____________ 4. TITLE AND SUBTITLE L FUMNING NUMBR A Mobile Robot Sonar System With Obstacle Avoidance (U

  18. Computer Model of a High-Resolution Imaging Sonar

    DTIC Science & Technology

    1990-07-01

    This is a very efficient method of obtaining imagcs in near-real-time. These sonars have found wide use in underwater vehicles and submersibles...perceived by an optical camera at the sonar location is generated by the method of range shading. This image serves as a reference for the subsequent efforts...Bhawan New Delhi, 110003 INDIA 10. Dr. V.P. Kodali Adviser Electronics Commission Lok Nayak Bhawan New Delhi, 110003 INDIA 11. Professor A.K. Jain

  19. Beaked Whales Respond to Simulated and Actual Navy Sonar

    PubMed Central

    Tyack, Peter L.; Zimmer, Walter M. X.; Moretti, David; Southall, Brandon L.; Claridge, Diane E.; Durban, John W.; Clark, Christopher W.; D'Amico, Angela; DiMarzio, Nancy; Jarvis, Susan; McCarthy, Elena; Morrissey, Ronald; Ward, Jessica; Boyd, Ian L.

    2011-01-01

    Beaked whales have mass stranded during some naval sonar exercises, but the cause is unknown. They are difficult to sight but can reliably be detected by listening for echolocation clicks produced during deep foraging dives. Listening for these clicks, we documented Blainville's beaked whales, Mesoplodon densirostris, in a naval underwater range where sonars are in regular use near Andros Island, Bahamas. An array of bottom-mounted hydrophones can detect beaked whales when they click anywhere within the range. We used two complementary methods to investigate behavioral responses of beaked whales to sonar: an opportunistic approach that monitored whale responses to multi-day naval exercises involving tactical mid-frequency sonars, and an experimental approach using playbacks of simulated sonar and control sounds to whales tagged with a device that records sound, movement, and orientation. Here we show that in both exposure conditions beaked whales stopped echolocating during deep foraging dives and moved away. During actual sonar exercises, beaked whales were primarily detected near the periphery of the range, on average 16 km away from the sonar transmissions. Once the exercise stopped, beaked whales gradually filled in the center of the range over 2–3 days. A satellite tagged whale moved outside the range during an exercise, returning over 2–3 days post-exercise. The experimental approach used tags to measure acoustic exposure and behavioral reactions of beaked whales to one controlled exposure each of simulated military sonar, killer whale calls, and band-limited noise. The beaked whales reacted to these three sound playbacks at sound pressure levels below 142 dB re 1 µPa by stopping echolocation followed by unusually long and slow ascents from their foraging dives. The combined results indicate similar disruption of foraging behavior and avoidance by beaked whales in the two different contexts, at exposures well below those used by regulators to define

  20. Development of Castor-Oil-Resistant Polyurethane Sonar Encapsulants.

    DTIC Science & Technology

    2014-09-26

    7D-S? 576 DEVELOPMENT OF CASTOR- OIL -RESISTANT POLYURETHANE SONAR 1/1 ENCRPSULANTS(U) NRVAL RESEARCH LAB MASHINGTON DC UNCLSSIFED T MA3URICE ET AL. 30...ACCESSION NO. Washington, DC 23062 64503N I S0219AS (59)0584 i1 TITLE (Include Security Classification) Development of Castor- Oil -Resistant...identify by block number) FIELD GROUP SUB-GROUP Castor oil -- Sonar transducer encapsulants 11 07 - Polyurethane\\ K , 19. ABSTRACT (Continue on reverse if

  1. Beaked whales respond to simulated and actual navy sonar.

    PubMed

    Tyack, Peter L; Zimmer, Walter M X; Moretti, David; Southall, Brandon L; Claridge, Diane E; Durban, John W; Clark, Christopher W; D'Amico, Angela; DiMarzio, Nancy; Jarvis, Susan; McCarthy, Elena; Morrissey, Ronald; Ward, Jessica; Boyd, Ian L

    2011-03-14

    Beaked whales have mass stranded during some naval sonar exercises, but the cause is unknown. They are difficult to sight but can reliably be detected by listening for echolocation clicks produced during deep foraging dives. Listening for these clicks, we documented Blainville's beaked whales, Mesoplodon densirostris, in a naval underwater range where sonars are in regular use near Andros Island, Bahamas. An array of bottom-mounted hydrophones can detect beaked whales when they click anywhere within the range. We used two complementary methods to investigate behavioral responses of beaked whales to sonar: an opportunistic approach that monitored whale responses to multi-day naval exercises involving tactical mid-frequency sonars, and an experimental approach using playbacks of simulated sonar and control sounds to whales tagged with a device that records sound, movement, and orientation. Here we show that in both exposure conditions beaked whales stopped echolocating during deep foraging dives and moved away. During actual sonar exercises, beaked whales were primarily detected near the periphery of the range, on average 16 km away from the sonar transmissions. Once the exercise stopped, beaked whales gradually filled in the center of the range over 2-3 days. A satellite tagged whale moved outside the range during an exercise, returning over 2-3 days post-exercise. The experimental approach used tags to measure acoustic exposure and behavioral reactions of beaked whales to one controlled exposure each of simulated military sonar, killer whale calls, and band-limited noise. The beaked whales reacted to these three sound playbacks at sound pressure levels below 142 dB re 1 µPa by stopping echolocation followed by unusually long and slow ascents from their foraging dives. The combined results indicate similar disruption of foraging behavior and avoidance by beaked whales in the two different contexts, at exposures well below those used by regulators to define

  2. Application of mobile robot localization using sonar

    SciTech Connect

    Byrd, J.S.; Hill, K.H.

    1994-12-31

    A sonar-based mobile robot has been developed for inspection of low-level radioactive waste drums. An algorithm was developed which gives the robot the ability to refence itself to cylindrical objects. The drum-following algorithm has been demonstrated in 4-ft drum aisles at the Mobile Robotics Laboratory at the University of South Carolina. The final version has proven to be robust through extensive long-term navigation tests. Future enhancements will employ a narrow-aisle version of the Nav-master to allow navigation in 3-ft drum aisles. The final version of the inspection robot will include the drum-navigation algorithm as a low-level primitive instruction. The onboard management system will be dedicated to more of the high-level functions, such as planning, now provided by the offboard supervisory system.

  3. Automated change detection for synthetic aperture sonar

    NASA Astrophysics Data System (ADS)

    G-Michael, Tesfaye; Marchand, Bradley; Tucker, J. D.; Sternlicht, Daniel D.; Marston, Timothy M.; Azimi-Sadjadi, Mahmood R.

    2014-05-01

    In this paper, an automated change detection technique is presented that compares new and historical seafloor images created with sidescan synthetic aperture sonar (SAS) for changes occurring over time. The method consists of a four stage process: a coarse navigational alignment; fine-scale co-registration using the scale invariant feature transform (SIFT) algorithm to match features between overlapping images; sub-pixel co-registration to improves phase coherence; and finally, change detection utilizing canonical correlation analysis (CCA). The method was tested using data collected with a high-frequency SAS in a sandy shallow-water environment. By using precise co-registration tools and change detection algorithms, it is shown that the coherent nature of the SAS data can be exploited and utilized in this environment over time scales ranging from hours through several days.

  4. Bistatic Sonar and Quantification of Seafloor Processes

    NASA Astrophysics Data System (ADS)

    McCloghrie, P.; BLONDEL, P.; Pace, N. G.; Heald, G. J.; Brothers, R.

    2001-12-01

    Sonar has proved the best tool for investigation of seafloor processes. Calibrated sonars provide a wealth of quantitative information unattainable through other means, but are limited to backscattering geometries, where the acoustic source and receiver are on the same platform. Recent developments in acoustic theory and design have shown the advantage of bistatic instruments, where the source and receiver(s) are physically decoupled and can be anywhere in the water column. Although there are many theoretical studies of bistatic scattering, their applicability is limited by the very low number of actual experiments. Using the large tank facilities at the University of Bath, we are currently investigating the bistatic scattering from several realistic types of seabeds and different morphologies, at high frequency (250 kHz). These studies are used in conjunction with state-of-the-art acoustic models (Blondel et al., 2001), and compared with data from complementary sea trials (Pace et al., in prep.). The results show the huge potential of bistatic systems for accurate and detailed mapping of seafloor structures and their topography. We also demonstrate how the relative contributions of surface and volume processes to acoustic scattering change with the imaging geometry, and how this can be used to maximise the information gained during mapping. Versatile and efficient, bistatic systems can be deployed from surface vessels, ROVs or AUVs. These new tools can be used for Rapid Environmental Assessment, to study sediment transport and deposition, and to access the detailed morphology of the seabed and the near sub-surface. They can in particular be used for the investigation of the small-scale structure of sand ridges and ripples, the distribution of tidal or glacial deposits on the seabed, and the quantification of multi-scale surface roughness in sedimentary and non-sedimentary terrains alike. Crown Copyright 2001 DERA. Published with the permission of the Defence

  5. BatSLAM: Simultaneous localization and mapping using biomimetic sonar.

    PubMed

    Steckel, Jan; Peremans, Herbert

    2013-01-01

    We propose to combine a biomimetic navigation model which solves a simultaneous localization and mapping task with a biomimetic sonar mounted on a mobile robot to address two related questions. First, can robotic sonar sensing lead to intelligent interactions with complex environments? Second, can we model sonar based spatial orientation and the construction of spatial maps by bats? To address these questions we adapt the mapping module of RatSLAM, a previously published navigation system based on computational models of the rodent hippocampus. We analyze the performance of the proposed robotic implementation operating in the real world. We conclude that the biomimetic navigation model operating on the information from the biomimetic sonar allows an autonomous agent to map unmodified (office) environments efficiently and consistently. Furthermore, these results also show that successful navigation does not require the readings of the biomimetic sonar to be interpreted in terms of individual objects/landmarks in the environment. We argue that the system has applications in robotics as well as in the field of biology as a simple, first order, model for sonar based spatial orientation and map building.

  6. The Satiety Signaling Neuropeptide Perisulfakinin Inhibits the Activity of Central Neurons Promoting General Activity

    PubMed Central

    Wicher, Dieter; Derst, Christian; Gautier, Hélène; Lapied, Bruno; Heinemann, Stefan H.; Agricola, Hans-Jürgen

    2007-01-01

    The metabolic state is one of the determinants of the general activity level. Satiety is related to resting or sleep whereas hunger correlates to wakefulness and activity. The counterpart to the mammalian satiety signal cholecystokinin (CCK) in insects are the sulfakinins. The aim of this study was to resolve the mechanism by which the antifeedant activity of perisulfakinin (PSK) in Periplaneta americana is mediated. We identified the sources of PSK which is used both as hormone and as paracrine messenger. PSK is found in the neurohemal organ of the brain and in nerve endings throughout the central nervous system. To correlate the distributions of PSK and its receptor (PSKR), we cloned the gene coding for PSKR and provide evidence for its expression within the nervous system. It occurs only in a few neurons, among them are the dorsal unpaired median (DUM) neurons which release octopamine thereby regulating the general level of activity. Application of PSK to DUM neurons attenuated the spiking frequency (EC50=11pM) due to reduction of a pacemaker Ca2+ current through cAMP-inhibited pTRPγ channels. PSK increased the intracellular cAMP level while decreasing the intracellular Ca2+ concentration in DUM neurons. Thus, the satiety signal conferred by PSK acts antagonistically to the hunger signal, provided by the adipokinetic hormone (AKH): PSK depresses the electrical activity of DUM neurons by inhibiting the pTRPγ channel that is activated by AKH under conditions of food shortage. PMID:18946521

  7. Deriving stellar inclination of slow rotators using stellar activity signal

    NASA Astrophysics Data System (ADS)

    Dumusque, Xavier

    2015-01-01

    Stellar inclination is an important parameter for many astrophysical studies. In the context of exoplanets, this allows us to derive the true obliquity of a system if the projected stellar spin-planetary orbit angle can measured via the Rossiter-Mclaughlin effect. Although different techniques allow us to estimate stellar inclination for fast rotators, it becomes much more difficult when stars are rotating slower than 2-2.5 km.s-1. By using the new activity simulation SOAP 2.0 that can reproduce the photometric and spectroscopic variations induced by stellar activity, we are able to fit the activity variation of solar-type stars and derive their inclination. The case of the equator-on star HD189733 will be presented, as well as the case of Alpha Centauri B, which present an inclination of 45+9-19 degrees, implying that the earth-mass orbiting planet is not transiting if aligned with its host star. Other exemples will also demonstrate the power of the technique, that can infer a stellar inclination, even for slow rotators like Alpha Centauri B, that present a projected rotational velocity smaller than 1.15 km.s-1. In addition, the SOAP 2.0 simulation can be used to correct for the effect of activity when one major active region is dominating the RV signal. This could enhance the detection of small mass exoplanets orbiting slightly active stars.This project is funded by ETAEARTH (European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement n. 313014), a transnational collaboration between European countries and the US (the Swiss Space Office, the Harvard Origin of Life Initiative, the Scottish Universities Physics Alliance, the University of Geneva, the Smithsonian Astrophysical Observatory, the Italian National Astrophysical Institute, the University of St. Andrews, Queens University Belfast, and the University of Edinburgh) setup to optimize the synergy between space-and ground-based data whose scientific potential for the characterization of

  8. Time-series measurements of hydrothermal plume volume flux with imaging sonar

    NASA Astrophysics Data System (ADS)

    Xu, G.; Jackson, D. R.; Bemis, K. G.; Rona, P. A.

    2012-12-01

    COVIS (Cabled Observatory Vent Imaging Sonar) is an innovative sonar system designed to quantitatively monitor the outputs of deep-sea hydrothermal vent clusters for both high-temperature focused vents and diffuse flows. In September 2010, COVIS was connected to the NEPTUNE Canada underwater ocean observatory network (http://www.NEPTUNEcanada.ca) at the Grotto vent cluster at the Main Endeavour Field on the Endeavour Segment of the Juan de Fuca Ridge. Since then, COVIS has been monitoring the hydrothermal plumes above Grotto by transmitting high-frequency (400 kHz), pulsed acoustic waves towards the plumes and recording the backscattered signals from each pulse, except for a one-year hiatus due to the power-off of the NEPTUNE Canada network between November 2010 and September 2011. The received backscatter signals are transmitted via the NEPTUNE Canada network to the land-based servers in real time, where a combination of automatic and manual data analyses produces a plume volume-flux and flow-rate time series using both the intensity and Doppler shift of the backscatter signals. The initial 30-day time series (Sep-Oct 2010) was presented in AGU Fall meeting, 2011. Evident short-term temporal variations (< 2 days) have been observed, which indicates significant interaction between the plume and the ambient tidal current oscillations. To further investigate such interaction and capture long-term patterns of the system, we present a 10-month time series (since the resumption of COVIS in September 2011 until present) of the volume flux and flow rate of the plume discharging from the North Tower of Grotto. The new time series, with a 3-hour sampling rate and long duration, can reveal the variations of the plume on a wide range of time scales (< 2 days ~ months). Compared with its predecessor, the new time series provides a better chance to capture the episodic events (e.g. geologically driven), low-frequency periodic (e.g. seasonal) oscillations, and long-term trend in

  9. Statistically normalized coherent change detection for synthetic aperture sonar imagery

    NASA Astrophysics Data System (ADS)

    G-Michael, Tesfaye; Tucker, J. D.; Roberts, Rodney G.

    2016-05-01

    Coherent Change Detection (CCD) is a process of highlighting an area of activity in scenes (seafloor) under survey and generated from pairs of synthetic aperture sonar (SAS) images of approximately the same location observed at two different time instances. The problem of CCD and subsequent anomaly feature extraction/detection is complicated due to several factors such as the presence of random speckle pattern in the images, changing environmental conditions, and platform instabilities. These complications make the detection of weak target activities even more difficult. Typically, the degree of similarity between two images measured at each pixel locations is the coherence between the complex pixel values in the two images. Higher coherence indicates little change in the scene represented by the pixel and lower coherence indicates change activity in the scene. Such coherence estimation scheme based on the pixel intensity correlation is an ad-hoc procedure where the effectiveness of the change detection is determined by the choice of threshold which can lead to high false alarm rates. In this paper, we propose a novel approach for anomalous change pattern detection using the statistical normalized coherence and multi-pass coherent processing. This method may be used to mitigate shadows by reducing the false alarms resulting in the coherent map due to speckles and shadows. Test results of the proposed methods on a data set of SAS images will be presented, illustrating the effectiveness of the normalized coherence in terms statistics from multi-pass survey of the same scene.

  10. Inhibition of constitutive signal transducer and activator of transcription 3 activation by novel platinum complexes with potent antitumor activity.

    PubMed

    Turkson, James; Zhang, Shumin; Palmer, Jay; Kay, Heidi; Stanko, Joseph; Mora, Linda B; Sebti, Said; Yu, Hua; Jove, Richard

    2004-12-01

    DNA-alkylating agents that are platinum complexes induce apoptotic responses and have wide application in cancer therapy. The potential for platinum compounds to modulate signal transduction events that contribute to their therapeutic outcome has not been extensively examined. Among the signal transducer and activator of transcription (STAT) proteins, Stat3 activity is frequently up-regulated in many human tumors. Various lines of evidence have established a causal role for aberrant Stat3 activity in malignant transformation and provided validation for its targeting in the development of small-molecule inhibitors as novel cancer therapeutics. We report here that platinum-containing compounds disrupt Stat3 signaling and suppress its biological functions. The novel platinum (IV) compounds, CPA-1, CPA-7, and platinum (IV) tetrachloride block Stat3 activity in vitro at low micromolar concentrations. In malignant cells that harbor constitutively activated Stat3, CPA-1, CPA-7, and platinum (IV) tetrachloride inhibit cell growth and induce apoptosis in a manner that reflects the attenuation of persistent Stat3 activity. By contrast, cells that do not contain persistent Stat3 activity are marginally affected or are not affected by these compounds. Moreover, CPA-7 induces the regression of mouse CT26 colon tumor, which correlates with the abrogation of persistent Stat3 activity in tumors. Thus, the modulation of oncogenic signal transduction pathways, such as Stat3, may be one of the key molecular mechanisms for the antitumor effects of platinum (IV)-containing complexes.

  11. PTEN controls immunoreceptor (immunoreceptor tyrosine-based activation motif) signaling and the activation of Rac.

    PubMed

    Kim, Jong Suk; Peng, Xiaodong; De, Pradip K; Geahlen, Robert L; Durden, Donald L

    2002-01-15

    Fcgamma receptor-mediated phagocytosis is a model for the study of immunoreceptor (immunoreceptor tyrosine-based activation motif [ITAM]) signaling and involves the activation of protein tyrosine kinases, protein tyrosine phosphatases, and downstream effectors including phosphatidylinositol-3 (PI-3) kinase. Relatively little is known of the role of lipid phosphatases in the control of ITAM signaling and inflammation. A heterologous COS7 cell system was used to examine the roles played by PI-3 kinase and the dual-specificity phosphatase, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), in the signal transduction pathway leading to Fcgamma receptor IIA-mediated phagocytosis and the activation of Rac. The expression of wildtype PTEN completely abrogated the phagocytosis of immunoglobulin-G-sensitized sheep red blood cells, as compared with the catalytically inactive mutant of PTEN, which had no effect. This is the first direct evidence that PTEN, an inositol 3' phosphatase, regulates Fcgamma receptor-mediated phagocytosis, an ITAM-based signaling event. The data suggest that PTEN exerts control over phagocytosis potentially by controlling the downstream conversion of guanosine diphosphate-Rac to guanosine triphosphate-Rac following ITAM stimulation.

  12. Regulators of G-protein Signaling accelerate GPCR signaling kinetics and govern sensitivity solely by accelerating GTPase activity

    PubMed Central

    Lambert, Nevin A.; Johnston, Christopher A.; Cappell, Steven D.; Kuravi, Sudhakiranmayi; Kimple, Adam J.; Willard, Francis S.; Siderovski, David P.

    2010-01-01

    G-protein heterotrimers, composed of a guanine nucleotide-binding Gα subunit and an obligate Gβγ dimer, regulate signal transduction pathways by cycling between GDP- and GTP-bound states. Signal deactivation is achieved by Gα-mediated GTP hydrolysis (GTPase activity) which is enhanced by the GTPase-accelerating protein (GAP) activity of “regulator of G-protein signaling” (RGS) proteins. In a cellular context, RGS proteins have also been shown to speed up the onset of signaling, and to accelerate deactivation without changing amplitude or sensitivity of the signal. This latter paradoxical activity has been variably attributed to GAP/enzymatic or non-GAP/scaffolding functions of these proteins. Here, we validated and exploited a Gα switch-region point mutation, known to engender increased GTPase activity, to mimic in cis the GAP function of RGS proteins. While the transition-state, GDP·AlF4 −-bound conformation of the G202A mutant was found to be nearly identical to wild-type, Gαi1(G202A)·GDP assumed a divergent conformation more closely resembling the GDP·AlF4 −-bound state. When placed within Saccharomyces cerevisiae Gα subunit Gpa1, the fast-hydrolysis mutation restored appropriate dose–response behaviors to pheromone signaling in the absence of RGS-mediated GAP activity. A bioluminescence resonance energy transfer (BRET) readout of heterotrimer activation with high temporal resolution revealed that fast intrinsic GTPase activity could recapitulate in cis the kinetic sharpening (increased onset and deactivation rates) and blunting of sensitivity also engendered by RGS protein action in trans. Thus Gα-directed GAP activity, the first biochemical function ascribed to RGS proteins, is sufficient to explain the activation kinetics and agonist sensitivity observed from G-protein–coupled receptor (GPCR) signaling in a cellular context. PMID:20351284

  13. Agonist-Biased Signaling via Proteinase Activated Receptor-2: Differential Activation of Calcium and Mitogen-Activated Protein Kinase Pathways

    PubMed Central

    Ramachandran, Rithwik; Mihara, Koichiro; Mathur, Maneesh; Rochdi, Moulay Driss; Bouvier, Michel; DeFea, Kathryn

    2009-01-01

    We evaluated the ability of different trypsin-revealed tethered ligand (TL) sequences of rat proteinase-activated receptor 2 (rPAR2) and the corresponding soluble TL-derived agonist peptides to trigger agonist-biased signaling. To do so, we mutated the proteolytically revealed TL sequence of rPAR2 and examined the impact on stimulating intracellular calcium transients and mitogen-activated protein (MAP) kinase. The TL receptor mutants, rPAR2-Leu37Ser38, rPAR2-Ala37–38, and rPAR2-Ala39–42 were compared with the trypsin-revealed wild-type rPAR2 TL sequence, S37LIGRL42—. Upon trypsin activation, all constructs stimulated MAP kinase signaling, but only the wt-rPAR2 and rPAR2-Ala39–42 triggered calcium signaling. Furthermore, the TL-derived synthetic peptide SLAAAA-NH2 failed to cause PAR2-mediated calcium signaling but did activate MAP kinase, whereas SLIGRL-NH2 triggered both calcium and MAP kinase signaling by all receptors. The peptides AAIGRL-NH2 and LSIGRL-NH2 triggered neither calcium nor MAP kinase signals. Neither rPAR2-Ala37–38 nor rPAR2-Leu37Ser38 constructs recruited β-arrestins-1 or -2 in response to trypsin stimulation, whereas both β-arrestins were recruited to these mutants by SLIGRL-NH2. The lack of trypsin-triggered β-arrestin interactions correlated with impaired trypsin-activated TL-mutant receptor internalization. Trypsin-stimulated MAP kinase activation by the TL-mutated receptors was not blocked by inhibitors of Gαi (pertussis toxin), Gαq [N-cyclohexyl-1-(2,4-dichlorophenyl)-1,4-dihydro-6-methylindeno[1,2-c]pyrazole-3-carboxamide (GP2A)], Src kinase [4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP1)], or the epidermal growth factor (EGF) receptor [4-(3′-chloroanilino)-6,7-dimethoxy-quinazoline (AG1478)], but was inhibited by the Rho-kinase inhibitor (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide, 2HCl (Y27362). The data indicate that the proteolytically revealed TL sequence(s) and the mode

  14. Implementation and testing of a Deep Water Correlation Velocity Sonar

    SciTech Connect

    Dickey, F.R.; Bookheimer, W.C.; Rhoades, K.W.

    1983-05-01

    The paper describes a new sonar designated the Magnavox MX 810 Deep Water Correlation Sonar which is under development by the General Electric Company and the Magnavox Advanced Products and Systems Company. The sonar measures ship's velocity relative to the bottom but instead of using the conventional doppler effect, it uses the correlation method described by Dickey and Edward in 1978. In this method, the narrow beams required for doppler are not needed and a low frequency that penetrates to the bottom in deep water is used. The sonar was designed with the constraint that it use a transducer that mounts through a single 12 inch gate valve. Most offshore geophysical surveys at present make use of an integrated navigation system with bottom referenced velocity input from a doppler sonar which, because of limitations on the sonar bottomtracking range, has difficulty in areas where the water depth is greater than about 500 meters. The MX 810 provides bottom tracking in regions of much greater water depth. It also may be applied as an aid in continuous positioning of a vessel over a fixed location. It also should prove useful as a more general navigation aid. The sonar is undergoing a series of tests using Magnavox's facilities for the purpose of verifying the performance and obtaining data to support and quantify planned improvements in both software and hardware. A prototype transducer of only 5 watts power output was used, but in spite of this low power, successful operation to depths of 1900 meters was obtained. Extrapolation to system parameters to be implemented in production models predicts operation to depths of 5000 meters.

  15. Signal Activation and Inactivation by the Gα Helical Domain: A Long-Neglected Partner in G Protein Signaling

    PubMed Central

    Dohlman, Henrik G.; Jones, Janice C.

    2013-01-01

    Heterotrimeric guanine nucleotide–binding proteins (G proteins) are positioned at the top of many signal transduction pathways. The G protein α subunit is composed of two domains, one that resembles Ras and another that is composed entirely of α helices. Historically, most attention has focused on the Ras-like domain, but emerging evidence reveals that the helical domain is an active participant in G protein signaling. PMID:22649098

  16. Akt1 signaling coordinates BMP signaling and β-catenin activity to regulate second heart field progenitor development.

    PubMed

    Luo, Wen; Zhao, Xia; Jin, Hengwei; Tao, Lichan; Zhu, Jingai; Wang, Huijuan; Hemmings, Brian A; Yang, Zhongzhou

    2015-02-15

    Second heart field (SHF) progenitors exhibit continued proliferation and delayed differentiation, which are modulated by FGF4/8/10, BMP and canonical Wnt/β-catenin signaling. PTEN-Akt signaling regulates the stem cell/progenitor cell homeostasis in several systems, such as hematopoietic stem cells, intestinal stem cells and neural progenitor cells. To address whether PTEN-Akt signaling is involved in regulating cardiac progenitors, we deleted Pten in SHF progenitors. Deletion of Pten caused SHF expansion and increased the size of the SHF derivatives, the right ventricle and the outflow tract. Cell proliferation of cardiac progenitors was enhanced, whereas cardiac differentiation was unaffected by Pten deletion. Removal of Akt1 rescued the phenotype and early lethality of Pten deletion mice, suggesting that Akt1 was the key downstream target that was negatively regulated by PTEN in cardiac progenitors. Furthermore, we found that inhibition of FOXO by Akt1 suppressed the expression of the gene encoding the BMP ligand (BMP7), leading to dampened BMP signaling in the hearts of Pten deletion mice. Cardiac activation of Akt also increased the Ser552 phosphorylation of β-catenin, thus enhancing its activity. Reducing β-catenin levels could partially rescue heart defects of Pten deletion mice. We conclude that Akt signaling regulates the cell proliferation of SHF progenitors through coordination of BMP signaling and β-catenin activity.

  17. A Computer Simulation Study of Station Keeping by an Autonomous Submersible Using Bottom-Tracking Sonar

    DTIC Science & Technology

    1988-06-01

    63 Figure 5.1 "Lock On" Illustration .................................................................... 68 Figure 5.2 Depth Below AUV / Sonar Range... AUV sonar scan mechanism in Earth coordinates. Given Equation (3.2), from Figure 3.8, the transformation from AUV coordinates to beam tip (end effector...0Cells inside circle = accessible cells =pi* r2 15 2 * pi = 706 accessible cells Depth Below AUV / Sonar Range Sonar Range 14.1 cell radius i RI 150 m depth

  18. Highly Directional Sonar Beam of Narwhals (Monodon monoceros) Measured with a Vertical 16 Hydrophone Array.

    PubMed

    Koblitz, Jens C; Stilz, Peter; Rasmussen, Marianne H; Laidre, Kristin L

    2016-01-01

    Recordings of narwhal (Monodon monoceros) echolocation signals were made using a linear 16 hydrophone array in the pack ice of Baffin Bay, West Greenland in 2013 at eleven sites. An average -3 dB beam width of 5.0° makes the narwhal click the most directional biosonar signal reported for any species to date. The beam shows a dorsal-ventral asymmetry with a narrower beam above the beam axis. This may be an evolutionary advantage for toothed whales to reduce echoes from the water surface or sea ice surface. Source level measurements show narwhal click intensities of up to 222 dB pp re 1 μPa, with a mean apparent source level of 215 dB pp re 1 μPa. During ascents and descents the narwhals perform scanning in the vertical plane with their sonar beam. This study provides valuable information for reference sonar parameters of narwhals and for the use of acoustic monitoring in the Arctic.

  19. Wall-Corner Classification Using Sonar: A New Approach Based on Geometric Features

    PubMed Central

    Martínez, Milagros; Benet, Ginés

    2010-01-01

    Ultrasonic signals coming from rotary sonar sensors in a robot gives us several features about the environment. This enables us to locate and classify the objects in the scenario of the robot. Each object and reflector produces a series of peaks in the amplitude of the signal. The radial and angular position of the sonar sensor gives information about location and their amplitudes offer information about the nature of the surface. Early works showed that the amplitude can be modeled and used to classify objects with very good results at short distances—80% average success in classifying both walls and corners at distances less than 1.5 m. In this paper, a new set of geometric features derived from the amplitude analysis of the echo is presented. These features constitute a set of characteristics that can be used to improve the results of classification at distances from 1.5 m to 4 m. Also, a comparative study on classification algorithms widely used in pattern recognition techniques has been carried out for sensor distances ranging between 0.5 to 4 m, and with incidence angles ranging between 20° to 70°. Experimental results show an enhancement on the success in classification rates when these geometric features are considered. PMID:22163493

  20. Highly Directional Sonar Beam of Narwhals (Monodon monoceros) Measured with a Vertical 16 Hydrophone Array

    PubMed Central

    Koblitz, Jens C.; Stilz, Peter; Rasmussen, Marianne H.; Laidre, Kristin L.

    2016-01-01

    Recordings of narwhal (Monodon monoceros) echolocation signals were made using a linear 16 hydrophone array in the pack ice of Baffin Bay, West Greenland in 2013 at eleven sites. An average -3 dB beam width of 5.0° makes the narwhal click the most directional biosonar signal reported for any species to date. The beam shows a dorsal-ventral asymmetry with a narrower beam above the beam axis. This may be an evolutionary advantage for toothed whales to reduce echoes from the water surface or sea ice surface. Source level measurements show narwhal click intensities of up to 222 dB pp re 1 μPa, with a mean apparent source level of 215 dB pp re 1 μPa. During ascents and descents the narwhals perform scanning in the vertical plane with their sonar beam. This study provides valuable information for reference sonar parameters of narwhals and for the use of acoustic monitoring in the Arctic. PMID:27828956

  1. Sunitinib activates Axl signaling in renal cell cancer.

    PubMed

    van der Mijn, Johannes C; Broxterman, Henk J; Knol, Jaco C; Piersma, Sander R; De Haas, Richard R; Dekker, Henk; Pham, Thang V; Van Beusechem, Victor W; Halmos, Balazs; Mier, James W; Jiménez, Connie R; Verheul, Henk M W

    2016-06-15

    Mass spectrometry-based phosphoproteomics provides a unique unbiased approach to evaluate signaling network in cancer cells. The tyrosine kinase inhibitor sunitinib is registered as treatment for patients with renal cell cancer (RCC). We investigated the effect of sunitinib on tyrosine phosphorylation in RCC tumor cells to get more insight in its mechanism of action and thereby to find potential leads for combination treatment strategies. Sunitinib inhibitory concentrations of proliferation (IC50) of 786-O, 769-p and A498 RCC cells were determined by MTT-assays. Global tyrosine phosphorylation was measured by LC-MS/MS after immunoprecipitation with the antiphosphotyrosine antibody p-TYR-100. Phosphoproteomic profiling of 786-O cells yielded 1519 phosphopeptides, corresponding to 675 unique proteins including 57 different phosphorylated protein kinases. Compared to control, incubation with sunitinib at its IC50 of 2 µM resulted in downregulation of 86 phosphopeptides including CDK5, DYRK3, DYRK4, G6PD, PKM and LDH-A, while 94 phosphopeptides including Axl, FAK, EPHA2 and p38α were upregulated. Axl- (y702), FAK- (y576) and p38α (y182) upregulation was confirmed by Western Blot in 786-O and A498 cells. Subsequent proliferation assays revealed that inhibition of Axl with a small molecule inhibitor (R428) sensitized 786-O RCC cells and immortalized endothelial cells to sunitinib up to 3 fold. In conclusion, incubation with sunitinib of RCC cells causes significant upregulation of multiple phosphopeptides including Axl. Simultaneous inhibition of Axl improves the antitumor activity of sunitinib. We envision that evaluation of phosphoproteomic changes by TKI treatment enables identification of new targets for combination treatment strategies.

  2. Sonar-induced temporary hearing loss in dolphins.

    PubMed

    Mooney, T Aran; Nachtigall, Paul E; Vlachos, Stephanie

    2009-08-23

    There is increasing concern that human-produced ocean noise is adversely affecting marine mammals, as several recent cetacean mass strandings may have been caused by animals' interactions with naval 'mid-frequency' sonar. However, it has yet to be empirically demonstrated how sonar could induce these strandings or cause physiological effects. In controlled experimental studies, we show that mid-frequency sonar can induce temporary hearing loss in a bottlenose dolphin (Tursiops truncatus). Mild-behavioural alterations were also associated with the exposures. The auditory effects were induced only by repeated exposures to intense sonar pings with total sound exposure levels of 214 dB re: 1 microPa(2) s. Data support an increasing energy model to predict temporary noise-induced hearing loss and indicate that odontocete noise exposure effects bear trends similar to terrestrial mammals. Thus, sonar can induce physiological and behavioural effects in at least one species of odontocete; however, exposures must be of prolonged, high sound exposures levels to generate these effects.

  3. Signal Transduction in T Cell Activation and Tolerance

    DTIC Science & Technology

    1993-01-01

    wealth of new information regarding the mechanism by which these surface receptors influence intracellular biochemical events. Transmembrane...Ltd 98 7 1 5 Vi 86 Basic MI | I L I IF a 86 Basic Mechanisms - How can an understanding of signal transduction aid in our understand- ing of T...distribution of the r consensus sequence suggests that it may represent a common mechanism used by a variety of immune system receptors to couple to signal

  4. Biological Signaling: the Role of ``Electrostatic Epicenter'' in ``Protein Quake'' and Receptor Activation

    NASA Astrophysics Data System (ADS)

    Xie, Aihua; Kaledhonkar, Sandip; Kang, Zhouyang; Hendriks, Johnny; Hellingwerf, Klaas

    2013-03-01

    Activation of a receptor protein during biological signaling is often characterized by a two state model: a receptor state (also called ``off state'') for detection of a stimuli, and a signaling state (``on state'') for signal relay. Receptor activation is a process that a receptor protein is structurally transformed from its receptor state to its signaling state through substantial conformational changes that are recognizable by its downstream signal relay partner. What are the structural and energetic origins for receptor activation in biological signaling? We report extensive evidence that further support the role of ``electrostatic epicenter'' in driving ``protein quake'' and receptor activation. Photoactive yellow protein (PYP), a bacterial blue light photoreceptor protein for the negative phototaxis of a salt loving Halorhodospira halophia, is employed as a model system in this study. We will discuss potential applications of this receptor activation mechanism to other receptor proteins, including B-RAF receptor protein that is associated with many cancers.

  5. Human ZCCHC12 activates AP-1 and CREB signaling as a transcriptional co-activator.

    PubMed

    Li, Hong; Liu, Qian; Hu, Xiang; Feng, Du; Xiang, Shuanglin; He, Zhicheng; Hu, Xingwang; Zhou, Jianlin; Ding, Xiaofeng; Zhou, Chang; Zhang, Jian

    2009-07-01

    Mouse zinc finger CCHC domain containing 12 gene (ZCCHC12) has been identified as a transcriptional co-activator of bone morphogenetic protein (BMP) signaling, and human ZCCHC12 was reported to be related to non-syndromic X-linked mental retardation (NS-XLMR). However, the details of how human ZCCHC12 involve in the NS-XLMR still remain unclear. In this study, we identified a novel nuclear localization signal (NLS) in the middle of human ZCCHC12 protein which is responsible for the nuclear localization. Multiple-tissue northern blot analysis indicated that ZCCHC12 is highly expressed in human brain. Furthermore, in situ hybridization showed that ZCCHC12 is specifically expressed in neuroepithelium of forebrain, midbrain, and diencephalon regions of mouse E10.5 embryos. Luciferase reporter assays demonstrated that ZCCHC12 enhanced the transcriptional activities of activator protein 1 (AP-1) and cAMP response element binding protein (CREB) as a coactivator. In conclusion, we identified a new NLS in ZCCHC12 and figured out that ZCCHC12 functions as a transcriptional co-activator of AP-1 and CREB.

  6. Validating side scan sonar as a fish survey tool

    NASA Astrophysics Data System (ADS)

    Bollinger, Michael A.

    Hydroacoustic methods can be used to answer a variety of questions regarding fish populations and behavior. In this study, side scan sonar methodology was developed to quantify abundance and biomass and compared to established visual observation methods on SCUBA over artificial reef structures in the western Gulf of Mexico. Side scan sonar methods were equivalent to SCUBA surveys for measuring fish abundance over the same reef areas, however, abundances were significantly higher when the larger area sampled by side scan was utilized. Side scan sonar methods were also more time efficient than SCUBA, ROV and long line fishing methods (66.7%, 33.3%, 25.9% respectively). In addition, side scan methods allowed biomass and fish size class categories to be estimated over reef sites. Side scan methods allowed five reef sites to be surveyed in one day, demonstrating the capability for macro scale comparisons of fish abundance, biomass and behavior among sites.

  7. Sonar surveys used in gas-storage cavern analysis

    SciTech Connect

    Crossley, N.G.

    1998-05-04

    Natural-gas storage cavern internal configuration, inspection information, and cavern integrity data can be obtained during high-pressure operations with specialized gas-sonar survey logging techniques. TransGas Ltd., Regina, Sask., has successfully performed these operations on several of its deepest and highest pressurized caverns. The data can determine gas-in-place inventory and assess changes in spatial volumes. These changes can result from cavern creep, shrinkage, or closure or from various downhole abnormalities such as fluid infill or collapse of the sidewall or roof. The paper discusses conventional surveys with sonar, running surveys in pressurized caverns, accuracy of the sonar survey, initial development of Cavern 5, a roof fall, Cavern 4 development, and a damaged string.

  8. Quantification of Diffuse Hydrothermal Flows Using Multibeam Sonar

    NASA Astrophysics Data System (ADS)

    Ivakin, A. N.; Jackson, D. R.; Bemis, K. G.; Xu, G.

    2014-12-01

    The Cabled Observatory Vent Imaging Sonar (COVIS) deployed at the Main Endeavour node of the NEPTUNE Canada observatory has provided acoustic time series extending over 2 years. This includes 3D images of plume scattering strength and Doppler velocity measurements as well as 2D images showing regions of diffuse flow. The diffuse-flow images display the level of decorrelation between sonar echos with transmissions separated by 0.2 s. The present work aims to provide further information on the strength of diffuse flows. Two approaches are used: Measurement of the dependence of decorrelation on lag and measurement of phase shift of sonar echos, with lags in 3-hour increments up to several days. The phase shifts and decorrelation are linked to variations of temperature above the seabed, which allows quantification of those variations, their magnitudes, spatial and temporal scales, and energy spectra. These techniques are illustrated using COVIS data obtained near the Grotto vent complex.

  9. Ecological echoes observed by moving biomimetic sonar characterize objects

    NASA Astrophysics Data System (ADS)

    Kuc, Roman

    2001-05-01

    This paper examines echoes from in situ foliage, similar to those observed by flying bats. A moving sonar converts echoes into spike sequences and applies neural-computational methods to estimate passing range and travel speed. Retro-reflectors and favorably oriented planar patches generate strong echoes (SEs), identified by spike firing rate. Linear sonar trajectories cause SEs to form hyperbolic patterns, termed glints, specified by passing range and travel speed. Passing-range specific detectors compare successive SE times with values in a table and tally coincidences. A glint terminates after a sufficient number of coincidences are tallied and two consecutive mismatches occur in the maximum-count detector. SE arrival jitter necessitates a coincidence window. Short windows identify individual glints while long windows generalize extended objects. SEs from distant objects exhibit almost constant incremental delays, used to estimate sonar travel speed, necessary for robust glint detection. Passing-range estimates may explain how bats can fly through small openings without collision.

  10. GSK621 Targets Glioma Cells via Activating AMP-Activated Protein Kinase Signalings

    PubMed Central

    Jiang, Hong; Liu, Wei; Zhan, Shi-Kun; Pan, Yi-Xin; Bian, Liu-Guan; Sun, Bomin; Sun, Qing-Fang; Pan, Si-Jian

    2016-01-01

    Here, we studied the anti-glioma cell activity by a novel AMP-activated protein kinase (AMPK) activator GSK621. We showed that GSK621 was cytotoxic to human glioma cells (U87MG and U251MG lines), possibly via provoking caspase-dependent apoptotic cell death. Its cytotoxicity was alleviated by caspase inhibitors. GSK621 activated AMPK to inhibit mammalian target of rapamycin (mTOR) and downregulate Tetraspanin 8 (Tspan8) in glioma cells. AMPK inhibition, through shRNA knockdown of AMPKα or introduction of a dominant negative (T172A) AMPKα, almost reversed GSK621-induced AMPK activation, mTOR inhibition and Tspan8 degradation. Consequently, GSK621’s cytotoxicity in glioma cells was also significantly attenuated by AMPKα knockdown or mutation. Further studies showed that GSK621, at a relatively low concentration, significantly potentiated temozolomide (TMZ)’s sensitivity and lethality against glioma cells. We summarized that GSK621 inhibits human glioma cells possibly via activating AMPK signaling. This novel AMPK activator could be a novel and promising anti-glioma cell agent. PMID:27532105

  11. Synaptic generation of an intracellular retrograde signal requires activation of the tyrosine kinase and mitogen-activated protein kinase signaling cascades in Aplysia.

    PubMed

    Stough, Shara; Kopec, Ashley M; Carew, Thomas J

    2015-11-01

    Cellular changes underlying memory formation can be generated in an activity-dependent manner at specific synapses. Thus an important question concerns the mechanisms by which synaptic signals communicate with the cell body to mediate these cellular changes. A monosynaptic circuit that is enhanced by sensitization in Aplysia is well-suited to study this question because three different subcellular compartments: (i) the sensorimotor SN-MN synapses, (ii) the SN projections to MNs via axonal connections, (iii) the SN cell bodies, can all be manipulated and studied independently. Here, we report that activity-dependent (AD) training in either the entire SN-MN circuit or in only the synaptic compartment, activates MAPK in a temporally and spatially specific pattern. Specifically, we find (i) MAPK activation is first transiently generated at SN-MN synapses during training, (ii) immediately after training MAPK is transiently activated in SN-MN axonal connections and persistently activated in SN cell bodies, and finally, (iii) MAPK is activated in SN cell bodies and SN-MN synapses 1h after training. These data suggest that there is an intracellularly transported retrograde signal generated at the synapse which is later responsible for delayed MAPK activation at SN somata. Finally, we find that this retrograde signal requires activation of tyrosine kinase (TK) and MEK signaling cascades at the synapses.

  12. AMP-activated Protein Kinase Signaling Activation by Resveratrol Modulates Amyloid-β Peptide Metabolism*

    PubMed Central

    Vingtdeux, Valérie; Giliberto, Luca; Zhao, Haitian; Chandakkar, Pallavi; Wu, Qingli; Simon, James E.; Janle, Elsa M.; Lobo, Jessica; Ferruzzi, Mario G.; Davies, Peter; Marambaud, Philippe

    2010-01-01

    Alzheimer disease is an age-related neurodegenerative disorder characterized by amyloid-β (Aβ) peptide deposition into cerebral amyloid plaques. The natural polyphenol resveratrol promotes anti-aging pathways via the activation of several metabolic sensors, including the AMP-activated protein kinase (AMPK). Resveratrol also lowers Aβ levels in cell lines; however, the underlying mechanism responsible for this effect is largely unknown. Moreover, the bioavailability of resveratrol in the brain remains uncertain. Here we show that AMPK signaling controls Aβ metabolism and mediates the anti-amyloidogenic effect of resveratrol in non-neuronal and neuronal cells, including in mouse primary neurons. Resveratrol increased cytosolic calcium levels and promoted AMPK activation by the calcium/calmodulin-dependent protein kinase kinase-β. Direct pharmacological and genetic activation of AMPK lowered extracellular Aβ accumulation, whereas AMPK inhibition reduced the effect of resveratrol on Aβ levels. Furthermore, resveratrol inhibited the AMPK target mTOR (mammalian target of rapamycin) to trigger autophagy and lysosomal degradation of Aβ. Finally, orally administered resveratrol in mice was detected in the brain where it activated AMPK and reduced cerebral Aβ levels and deposition in the cortex. These data suggest that resveratrol and pharmacological activation of AMPK have therapeutic potential against Alzheimer disease. PMID:20080969

  13. Echolocation with bat buzz emissions: model and biomimetic sonar for elevation estimation.

    PubMed

    Kuc, Roman

    2012-01-01

    Just prior to capture the Buzz II emissions of some mouth-emitting bats, such as Eptesicus fuscus, are observed to exhibit spectra having multiple peaks. This paper proposes an echolocation strategy that uses such spectra with energy concentrated in specific frequency bands for determining target elevation. A biomimetic sonar was implemented to produce a tri-modal spectrum by driving a speaker with a signal rich in harmonics. The emission magnitudes at these harmonic frequencies measured as a function of elevation in the zero-azimuth plane form distinct beams. A template was formed from the ratio of the first harmonic and fundamental magnitudes to determine elevation. The elevation estimator exhibited a sub-degree accuracy (SD = 0.4° over a 20° interval centered at the elevation at which these two beams intersect in the zero-azimuth plane. Spectral cues from -40° to +10° elevation allow a qualitative non-linear control of sonar orientation to drive the target to the beam-intersection point where quantitative elevation estimates are available.

  14. Investigation of sonar transponders for offshore wind farms: modeling approach, experimental setup, and results.

    PubMed

    Fricke, Moritz B; Rolfes, Raimund

    2013-11-01

    The installation of offshore wind farms in the German Exclusive Economic Zone requires the deployment of sonar transponders to prevent collisions with submarines. The general requirements for these systems have been previously worked out by the Research Department for Underwater Acoustics and Marine Geophysics of the Bundeswehr. In this article, the major results of the research project "Investigation of Sonar Transponders for Offshore Wind Farms" are presented. For theoretical investigations a hybrid approach was implemented using the boundary element method to calculate the source directivity and a three-dimensional ray-tracing algorithm to estimate the transmission loss. The angle-dependence of the sound field as well as the weather-dependence of the transmission loss are compared to experimental results gathered at the offshore wind farm alpha ventus, located 45 km north of the island Borkum. While theoretical and experimental results are in general agreement, the implemented model slightly underestimates scattering at the rough sea surface. It is found that the source level of 200 dB re 1 μPa at 1 m is adequate to satisfy the detectability of the warning sequence at distances up to 2 NM (≈3.7 km) within a horizontal sector of ±60° if realistic assumptions about signal-processing and noise are made. An arrangement to enlarge the angular coverage is discussed.

  15. Calcium signaling and the MAPK cascade are required for sperm activation in Caenorhabditis elegans.

    PubMed

    Liu, Zhiyu; Wang, Bin; He, Ruijun; Zhao, Yanmei; Miao, Long

    2014-02-01

    In nematode, sperm activation (or spermiogenesis), a process in which the symmetric and non-motile spermatids transform into polarized and crawling spermatozoa, is critical for sperm cells to acquire fertilizing competence. SPE-8 dependent and SPE-8 independent pathways function redundantly during sperm activation in both males and hermaphrodites of Caenorhabditis elegans. However, the downstream signaling for both pathways remains unclear. Here we show that calcium signaling and the MAPK cascade are required for both SPE-8 dependent and SPE-8 independent sperm activation, implying that both pathways share common downstream signaling components during sperm activation. We demonstrate that activation of the MAPK cascade is sufficient to activate spermatids derived from either wild-type or spe-8 group mutant males and that activation of the MAPK cascade bypasses the requirement of calcium signal to induce sperm activation, indicating that the MAPK cascade functions downstream of or parallel with the calcium signaling during sperm activation. Interestingly, the persistent activation of MAPK in activated spermatozoa inhibits Major Sperm Protein (MSP)-based cytoskeleton dynamics. We demonstrate that MAPK plays dual roles in promoting pseudopod extension during sperm activation but also blocking the MSP-based, amoeboid motility of the spermatozoa. Thus, though nematode sperm are crawling cells, morphologically distinct from flagellated sperm, and the molecular machinery for motility of amoeboid and flagellated sperm is different, both types of sperm might utilize conserved signaling pathways to modulate sperm maturation.

  16. Kurarinol induces hepatocellular carcinoma cell apoptosis through suppressing cellular signal transducer and activator of transcription 3 signaling

    SciTech Connect

    Shu, Guangwen; Yang, Jing; Zhao, Wenhao; Xu, Chan; Hong, Zongguo; Mei, Zhinan; Yang, Xinzhou

    2014-12-01

    Kurarinol is a flavonoid isolated from roots of the medical plant Sophora flavescens. However, its cytotoxic activity against hepatocellular carcinoma (HCC) cells and toxic effects on mammalians remain largely unexplored. Here, the pro-apoptotic activities of kurarinol on HCC cells and its toxic impacts on tumor-bearing mice were evaluated. The molecular mechanisms underlying kurarinol-induced HCC cell apoptosis were also investigated. We found that kurarinol dose-dependently provoked HepG2, Huh-7 and H22 HCC cell apoptosis. In addition, kurarinol gave rise to a considerable decrease in the transcriptional activity of signal transducer and activator of transcription 3 (STAT3) in HCC cells. Suppression of STAT3 signaling is involved in kurarinol-induced HCC cell apoptosis. In vivo studies showed that kurarinol injection substantially induced transplanted H22 cell apoptosis with low toxic impacts on tumor-bearing mice. Similarly, the transcriptional activity of STAT3 in transplanted tumor tissues was significantly suppressed after kurarinol treatment. Collectively, our current research demonstrated that kurarinol has the capacity of inducing HCC cell apoptosis both in vitro and in vivo with undetectable toxic impacts on the host. Suppressing STAT3 signaling is implicated in kurarinol-mediated HCC cell apoptosis. - Highlights: • Kurarinol induces hepatocellular carcinoma (HCC) cell apoptosis. • Kurarinol induces HCC cell apoptosis via inhibiting STAT3. • Kurarinol exhibits low toxic effects on tumor-bearing animals.

  17. Seafloor image survey of Juk-byeon port in Uljin, South Korea, using side scan sonar with a fixed long frame

    NASA Astrophysics Data System (ADS)

    Kim, W. H.; Park, C.; Lee, M.; Park, H. Y.; Kim, C.

    2015-12-01

    A side scan sonar launches ultrasonic wave from both sides of the transducer. And it restores the image by receiving signals. It measures the strength of how "loud" the return echo is, and paints a picture. Hard areas of the sea floor like rocks reflect more return signal than softer areas like sand. We conducted seafloor image survey from 4, Mar. 2013 using R/V Jangmok2 (35ton), side scan sonar 4125 (Edge Tech corporation). The side scan sonar system (4125) is a dual frequency system of 400/900kHz. Seafloor image survey is commonly used to tow the sensor in the rear side of vessel. However, we fixed the tow-fish on right side of the vessel in the seawater with a long frame. The mounted side scan sonar survey was useful in shallow water like the port having many obstacles. And we conducted submarine topography using multi-beam echo sounder EM3001 (Kongs-berg corporation). Multi-beam echo sounder is a device for observing and recording the submarine topography using sound. We mounted the EM3001 on right side of the vessel. Multi-beam echo sounder transducer commonly to mount at right angles to the surface of water. However, we tilted 20-degrees of transducer for long range with 85-degrees measurement on the right side of the vessel. We were equipped with a motion sensor, DGPS(Differential Global Positioning System), and SV(Sound velocity) sensor for the vessel's motion compensation, vessel's position, and the velocity of sound of seawater. The surveys showed the sediment, waste materials, and a lot of discarded tires accumulated in the port. The maximum depth was 12m in the port. Such multi-beam echo sounder survey and side scan sonar survey will facilitate the management and the improvement of environment of port.

  18. Danger signals activating the immune response after trauma.

    PubMed

    Hirsiger, Stefanie; Simmen, Hans-Peter; Werner, Clément M L; Wanner, Guido A; Rittirsch, Daniel

    2012-01-01

    Sterile injury can cause a systemic inflammatory response syndrome (SIRS) that resembles the host response during sepsis. The inflammatory response following trauma comprises various systems of the human body which are cross-linked with each other within a highly complex network of inflammation. Endogenous danger signals (danger-associated molecular patterns; DAMPs; alarmins) as well as exogenous pathogen-associated molecular patterns (PAMPs) play a crucial role in the initiation of the immune response. With popularization of the "danger theory," numerous DAMPs and PAMPs and their corresponding pathogen-recognition receptors have been identified. In this paper, we highlight the role of the DAMPs high-mobility group box protein 1 (HMGB1), interleukin-1α (IL-1α), and interleukin-33 (IL-33) as unique dual-function mediators as well as mitochondrial danger signals released upon cellular trauma and necrosis.

  19. SONAR Discovers RNA-Binding Proteins from Analysis of Large-Scale Protein-Protein Interactomes.

    PubMed

    Brannan, Kristopher W; Jin, Wenhao; Huelga, Stephanie C; Banks, Charles A S; Gilmore, Joshua M; Florens, Laurence; Washburn, Michael P; Van Nostrand, Eric L; Pratt, Gabriel A; Schwinn, Marie K; Daniels, Danette L; Yeo, Gene W

    2016-10-20

    RNA metabolism is controlled by an expanding, yet incomplete, catalog of RNA-binding proteins (RBPs), many of which lack characterized RNA binding domains. Approaches to expand the RBP repertoire to discover non-canonical RBPs are currently needed. Here, HaloTag fusion pull down of 12 nuclear and cytoplasmic RBPs followed by quantitative mass spectrometry (MS) demonstrates that proteins interacting with multiple RBPs in an RNA-dependent manner are enriched for RBPs. This motivated SONAR, a computational approach that predicts RNA binding activity by analyzing large-scale affinity precipitation-MS protein-protein interactomes. Without relying on sequence or structure information, SONAR identifies 1,923 human, 489 fly, and 745 yeast RBPs, including over 100 human candidate RBPs that contain zinc finger domains. Enhanced CLIP confirms RNA binding activity and identifies transcriptome-wide RNA binding sites for SONAR-predicted RBPs, revealing unexpected RNA binding activity for disease-relevant proteins and DNA binding proteins.

  20. Mammary ductal growth is impaired in mice lacking leptin-dependent signal transducer and activator of transcription 3 signaling.

    PubMed

    Thorn, Stephanie R; Giesy, Sarah L; Myers, Martin G; Boisclair, Yves R

    2010-08-01

    Mice lacking leptin (ob/ob) or its full-length receptor (db/db) are obese and reproductively incompetent. Fertility, pregnancy, and lactation are restored, respectively, in ob/ob mice treated with leptin through mating, d 6.5 post coitum, and pregnancy. Therefore, leptin signaling is needed for lactation, but the timing of its action and the affected mammary process remain unknown. To address this issue, we used s/s mice lacking only leptin-dependent signal transducer and activator of transcription (STAT)3 signaling. These mice share many features with db/db mice, including obesity, but differ by retaining sufficient activity of the hypothalamic-pituitary-ovarian axis to support reproduction. The s/s mammary epithelium was normal at 3 wk of age but failed to expand through the mammary fat pad (MFP) during the subsequent pubertal period. Ductal growth failure was not corrected by estrogen therapy and did not relate to inadequate IGF-I production by the MFP or to the need for epithelial or stromal leptin-STAT3 signaling. Ductal growth failure coincided with adipocyte hypertrophy and increased MFP production of leptin, TNFalpha, and IL6. These cytokines, however, were unable to inhibit the proliferation of a collection of mouse mammary epithelial cell lines. In conclusion, the very first step of postnatal mammary development fails in s/s mice despite sufficient estrogen IGF-I and an hypothalamic-pituitary-ovarian axis capable of supporting reproduction. This failure is not caused by mammary loss of leptin-dependent STAT3 signaling or by the development of inflammation. These data imply the existence of an unknown mechanism whereby leptin-dependent STAT3 signaling and obesity alter mammary ductal development.

  1. Oligodendrocyte-specific activation of PERK signaling protects mice against experimental autoimmune encephalomyelitis.

    PubMed

    Lin, Wensheng; Lin, Yifeng; Li, Jin; Fenstermaker, Ali G; Way, Sharon W; Clayton, Benjamin; Jamison, Stephanie; Harding, Heather P; Ron, David; Popko, Brian

    2013-04-03

    There is compelling evidence that oligodendrocyte apoptosis, in response to CNS inflammation, contributes significantly to the development of the demyelinating disorder multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Therefore, approaches designed to protect oligodendrocytes would likely have therapeutic value. Activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum (ER) stress increases cell survival under various cytotoxic conditions. Moreover, there is evidence that PERK signaling is activated in oligodendrocytes within demyelinating lesions in multiple sclerosis and EAE. Our previous study demonstrated that CNS delivery of the inflammatory cytokine interferon-γ before EAE onset protected mice against EAE, and this protection was dependent on PERK signaling. In our current study, we sought to elucidate the role of PERK signaling in oligodendrocytes during EAE. We generated transgenic mice that allow for temporally controlled activation of PERK signaling, in the absence of ER stress, specifically in oligodendrocytes. We demonstrated that persistent activation of PERK signaling was not deleterious to oligodendrocyte viability or the myelin of adult animals. Importantly, we found that enhanced activation of PERK signaling specifically in oligodendrocytes significantly attenuated EAE disease severity, which was associated with reduced oligodendrocyte apoptosis, demyelination, and axonal degeneration. This effect was not the result of an altered degree of the inflammatory response in EAE mice. Our results provide direct evidence that activation of PERK signaling in oligodendrocytes is cytoprotective, protecting mice against EAE.

  2. Integration of light and metabolic signals for stem cell activation at the shoot apical meristem

    PubMed Central

    Pfeiffer, Anne; Janocha, Denis; Dong, Yihan; Medzihradszky, Anna; Schöne, Stefanie; Daum, Gabor; Suzaki, Takuya; Forner, Joachim; Langenecker, Tobias; Rempel, Eugen; Schmid, Markus; Wirtz, Markus; Hell, Rüdiger; Lohmann, Jan U

    2016-01-01

    A major feature of embryogenesis is the specification of stem cell systems, but in contrast to the situation in most animals, plant stem cells remain quiescent until the postembryonic phase of development. Here, we dissect how light and metabolic signals are integrated to overcome stem cell dormancy at the shoot apical meristem. We show on the one hand that light is able to activate expression of the stem cell inducer WUSCHEL independently of photosynthesis and that this likely involves inter-regional cytokinin signaling. Metabolic signals, on the other hand, are transduced to the meristem through activation of the TARGET OF RAPAMYCIN (TOR) kinase. Surprisingly, TOR is also required for light signal dependent stem cell activation. Thus, the TOR kinase acts as a central integrator of light and metabolic signals and a key regulator of stem cell activation at the shoot apex. DOI: http://dx.doi.org/10.7554/eLife.17023.001 PMID:27400267

  3. Leukemia inhibitory factor and NGF regulate signal transducers and activators of transcription activation in sympathetic ganglia: convergence of cytokine- and neurotrophin-signaling pathways.

    PubMed

    Rajan, P; Gearan, T; Fink, J S

    1998-08-17

    We have used the response of the superior cervical ganglia (SCG) to axotomy to investigate interactions between neuropoietic cytokines and neurotrophins. Postganglionic sympathetic axotomy leads to a prolonged leukemia inhibitory factor (LIF)-dependent activation of signal transducers and activators of transcription (STAT) factors. To study regulation of LIF-dependent activation of STAT proteins and to mimic the loss of target-derived NGF resulting from postganglionic axotomy in vivo, SCG were explanted into media lacking NGF and activation of STAT proteins was assessed by electrophoretic mobility shift assay. Like postganglionic axotomy in vivo. STAT proteins were activated for up to 8 days after explantation of SCG in vitro. SCG cultured in the presence of NGF showed decreased STAT binding when compared to ganglia cultured in NGF-free media. This inhibition of STAT activation by NGF was only present in ganglia cultured for more than 5 days and was mimicked by brain-derived neurotrophic factor (BDNF). The serine kinase inhibitor H7 augmented the increase of STAT binding produced by explantation, suggesting the presence of a labile repressor of STAT activation in the SCG. These data indicated that the neuropoietic cytokine-signaling pathway interacts with neurotrophin and H7-sensitive-signaling pathways to regulate activation of STAT proteins in sympathetic neurons. Moreover, these data suggest that one of the mechanisms leading to prolonged activation of STAT proteins after postganglionic axotomy in vivo is loss of target-derived neurotrophins.

  4. GM-PHD filter multitarget tracking in sonar images

    NASA Astrophysics Data System (ADS)

    Clark, Daniel; Vo, Ba-Ngu; Bell, Judith

    2006-05-01

    The Gaussian Mixure Probability Hypothesis Density (GM-PHD) Multi-target Tracker was developed as an extension to the GM-PHD filter to provide track continuity. The algorithm is demonstrated on forward-looking sonar data with clutter and is compared with the results from the Particle PHD filter.

  5. A Rolling Line Source for a Seismic Sonar

    DTIC Science & Technology

    2002-06-01

    first used for bottom sounding and echolocation in the early 20th century by the French scientist Paul Langevin, a friend of the famous chemist Madam ...Marie Curie . Now acoustic sonars are well developed, and are an integral part of every warship, worldwide. Seismic interface waves, such as

  6. Enhanced Sidescan-Sonar Imagery Offshore of Southeastern Massachusetts

    USGS Publications Warehouse

    Poppe, Lawrence J.; McMullen, Kate Y.; Williams, S. Jeffress; Ackerman, Seth D.; Glomb, K.A.; Forfinski, N.A.

    2008-01-01

    The U.S. Geological Survey (USGS), National Oceanic and Atmospheric Administration (NOAA), and Massachusetts Office of Coastal Zone Management (CZM) have been working cooperatively to map and study the coastal sea floor. The sidescan-sonar imagery collected during NOAA hydrographic surveys has been included as part of these studies. However, the original sonar imagery contains tonal artifacts from environmental noise (for example, sea state), equipment settings (for example, power and gain changes), and processing (for example, inaccurate cross-track and line-to-line normalization), which impart a quilt-like patchwork appearance to the mosaics. These artifacts can obscure the normalized backscatter properties of the sea floor. To address this issue, sidescan-sonar imagery from surveys H11076 and H11079 offshore of southeastern Massachusetts was enhanced by matching backscatter tones of adjacent sidescan-sonar lines. These mosaics provide continuous grayscale perspectives of the backscatter, more accurately reveal the sea-floor geologic trends, and minimize the environment-, acquisition-, and processing-related noise.

  7. Activation of Ca(2+) -activated Cl(-) channel ANO1 by localized Ca(2+) signals.

    PubMed

    Jin, Xin; Shah, Sihab; Du, Xiaona; Zhang, Hailin; Gamper, Nikita

    2016-01-01

    Ca(2+)-activated chloride channels (CaCCs) regulate numerous physiological processes including epithelial transport, smooth muscle contraction and sensory processing. Anoctamin-1 (ANO1, TMEM16A) is a principal CaCC subunit in many cell types, yet our understanding of the mechanisms of ANO1 activation and regulation are only beginning to emerge. Ca(2+) sensitivity of ANO1 is rather low and at negative membrane potentials the channel requires several micromoles of intracellular Ca(2+) for activation. However, global Ca(2+) levels in cells rarely reach such levels and, therefore, there must be mechanisms that focus intracellular Ca(2+) transients towards the ANO1 channels. Recent findings indeed indicate that ANO1 channels often co-localize with sources of intracellular Ca(2+) signals. Interestingly, it appears that in many cell types ANO1 is particularly tightly coupled to the Ca(2+) release sites of the intracellular Ca(2+) stores. Such preferential coupling may represent a general mechanism of ANO1 activation in native tissues.

  8. Angiogenic activity of sesamin through the activation of multiple signal pathways

    SciTech Connect

    Chung, Byung-Hee; Lee, Jung Joon; Kim, Jong-Dai; Jeoung, Dooil; Lee, Hansoo; Choe, Jongseon; Ha, Kwon-Soo; Kwon, Young-Geun; Kim, Young-Myeong

    2010-01-01

    The natural product sesamin has been known to act as a potent antioxidant and prevent endothelial dysfunction. We here found that sesamin increased in vitro angiogenic processes, such as endothelial cell proliferation, migration, and tube formation, as well as neovascularization in an animal model. This compound elicited the activation of multiple angiogenic signal modulators, such as ERK, Akt, endothelial nitric oxide synthase (eNOS), NO production, FAK, and p38 MAPK, but not Src. The MEK inhibitor PD98059 and the PI3K inhibitor Wortmannin specifically inhibited sesamin-induced activation of the ERK and Akt/eNOS pathways. These inhibitors reduced angiogenic events, with high specificity for MEK/ERK-dependent cell proliferation and migration and PI3K/Akt-mediated tube formation. Moreover, inhibition of p38 MAPK effectively inhibited sesamin-induced cell migration. The angiogenic activity of sesamin was not associated with VEGF expression. Furthermore, this compound did not induce vascular permeability and upregulated ICAM-1 and VCAM-1 expression, which are hallmarks of vascular inflammation. These results suggest that sesamin stimulates angiogenesis in vitro and in vivo through the activation of MEK/ERK-, PI3K/Akt/eNOS-, p125{sup FAK}-, and p38 MAPK-dependent pathways, without increasing vascular inflammation, and may be used for treating ischemic diseases and tissue regeneration.

  9. Estimated Tissue and Blood N(2) Levels and Risk of Decompression Sickness in Deep-, Intermediate-, and Shallow-Diving Toothed Whales during Exposure to Naval Sonar.

    PubMed

    Kvadsheim, P H; Miller, P J O; Tyack, P L; Sivle, L D; Lam, F P A; Fahlman, A

    2012-01-01

    Naval sonar has been accused of causing whale stranding by a mechanism which increases formation of tissue N(2) gas bubbles. Increased tissue and blood N(2) levels, and thereby increased risk of decompression sickness (DCS), is thought to result from changes in behavior or physiological responses during diving. Previous theoretical studies have used hypothetical sonar-induced changes in both behavior and physiology to model blood and tissue N(2) tension [Formula: see text], but this is the first attempt to estimate the changes during actual behavioral responses to sonar. We used an existing mathematical model to estimate blood and tissue N(2) tension [Formula: see text] from dive data recorded from sperm, killer, long-finned pilot, Blainville's beaked, and Cuvier's beaked whales before and during exposure to Low- (1-2 kHz) and Mid- (2-7 kHz) frequency active sonar. Our objectives were: (1) to determine if differences in dive behavior affects risk of bubble formation, and if (2) behavioral- or (3) physiological responses to sonar are plausible risk factors. Our results suggest that all species have natural high N(2) levels, with deep diving generally resulting in higher end-dive [Formula: see text] as compared with shallow diving. Sonar exposure caused some changes in dive behavior in both killer whales, pilot whales and beaked whales, but this did not lead to any increased risk of DCS. However, in three of eight exposure session with sperm whales, the animal changed to shallower diving, and in all these cases this seem to result in an increased risk of DCS, although risk was still within the normal risk range of this species. When a hypothetical removal of the normal dive response (bradycardia and peripheral vasoconstriction), was added to the behavioral response during model simulations, this led to an increased variance in the estimated end-dive N(2) levels, but no consistent change of risk. In conclusion, we cannot rule out the possibility that a combination

  10. Estimated Tissue and Blood N2 Levels and Risk of Decompression Sickness in Deep-, Intermediate-, and Shallow-Diving Toothed Whales during Exposure to Naval Sonar

    PubMed Central

    Kvadsheim, P. H.; Miller, P. J. O.; Tyack, P. L.; Sivle, L. D.; Lam, F. P. A.; Fahlman, A.

    2012-01-01

    Naval sonar has been accused of causing whale stranding by a mechanism which increases formation of tissue N2 gas bubbles. Increased tissue and blood N2 levels, and thereby increased risk of decompression sickness (DCS), is thought to result from changes in behavior or physiological responses during diving. Previous theoretical studies have used hypothetical sonar-induced changes in both behavior and physiology to model blood and tissue N2 tension PN2, but this is the first attempt to estimate the changes during actual behavioral responses to sonar. We used an existing mathematical model to estimate blood and tissue N2 tension PN2 from dive data recorded from sperm, killer, long-finned pilot, Blainville’s beaked, and Cuvier’s beaked whales before and during exposure to Low- (1–2 kHz) and Mid- (2–7 kHz) frequency active sonar. Our objectives were: (1) to determine if differences in dive behavior affects risk of bubble formation, and if (2) behavioral- or (3) physiological responses to sonar are plausible risk factors. Our results suggest that all species have natural high N2 levels, with deep diving generally resulting in higher end-dive PN2 as compared with shallow diving. Sonar exposure caused some changes in dive behavior in both killer whales, pilot whales and beaked whales, but this did not lead to any increased risk of DCS. However, in three of eight exposure session with sperm whales, the animal changed to shallower diving, and in all these cases this seem to result in an increased risk of DCS, although risk was still within the normal risk range of this species. When a hypothetical removal of the normal dive response (bradycardia and peripheral vasoconstriction), was added to the behavioral response during model simulations, this led to an increased variance in the estimated end-dive N2 levels, but no consistent change of risk. In conclusion, we cannot rule out the possibility that a combination of behavioral and physiological responses to sonar

  11. Reliability of fish size estimates obtained from multibeam imaging sonar

    USGS Publications Warehouse

    Hightower, Joseph E.; Magowan, Kevin J.; Brown, Lori M.; Fox, Dewayne A.

    2013-01-01

    Multibeam imaging sonars have considerable potential for use in fisheries surveys because the video-like images are easy to interpret, and they contain information about fish size, shape, and swimming behavior, as well as characteristics of occupied habitats. We examined images obtained using a dual-frequency identification sonar (DIDSON) multibeam sonar for Atlantic sturgeon Acipenser oxyrinchus oxyrinchus, striped bass Morone saxatilis, white perch M. americana, and channel catfish Ictalurus punctatus of known size (20–141 cm) to determine the reliability of length estimates. For ranges up to 11 m, percent measurement error (sonar estimate – total length)/total length × 100 varied by species but was not related to the fish's range or aspect angle (orientation relative to the sonar beam). Least-square mean percent error was significantly different from 0.0 for Atlantic sturgeon (x̄  =  −8.34, SE  =  2.39) and white perch (x̄  = 14.48, SE  =  3.99) but not striped bass (x̄  =  3.71, SE  =  2.58) or channel catfish (x̄  = 3.97, SE  =  5.16). Underestimating lengths of Atlantic sturgeon may be due to difficulty in detecting the snout or the longer dorsal lobe of the heterocercal tail. White perch was the smallest species tested, and it had the largest percent measurement errors (both positive and negative) and the lowest percentage of images classified as good or acceptable. Automated length estimates for the four species using Echoview software varied with position in the view-field. Estimates tended to be low at more extreme azimuthal angles (fish's angle off-axis within the view-field), but mean and maximum estimates were highly correlated with total length. Software estimates also were biased by fish images partially outside the view-field and when acoustic crosstalk occurred (when a fish perpendicular to the sonar and at relatively close range is detected in the side lobes of adjacent beams). These sources of

  12. Irreversible Catalyst Activation Enables Hyperpolarization and Water Solubility for NMR Signal Amplification by Reversible Exchange

    DTIC Science & Technology

    2016-09-12

    Irreversible Catalyst Activation Enables Hyperpolarization and Water Solubility for NMR Signal Amplification by Reversible Exchange Milton L. Truong...Supporting Information ABSTRACT: Activation of a catalyst [IrCl(COD)(IMes)] (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene; COD = cyclooctadiene...for signal amplification by reversible exchange (SABRE) was monitored by in situ hyperpolarized proton NMR at 9.4 T. During the catalyst -activation

  13. Choline-releasing glycerophosphodiesterase EDI3 links the tumor metabolome to signaling network activities

    PubMed Central

    Marchan, Rosemarie; Lesjak, Michaela S.; Stewart, Joanna D.; Winter, Roland; Seeliger, Janine; Hengstler, Jan G.

    2012-01-01

    Recently, EDI3 was identified as a key factor for choline metabolism that controls tumor cell migration and is associated with metastasis in endometrial carcinomas. EDI3 cleaves glycerophosphocholine (GPC) to form choline and glycerol-3-phosphate (G3P). Choline is then further metabolized to phosphatidylcholine (PtdC), the major lipid in membranes and a key player in membrane-mediated cell signaling. The second product, G3P, is a precursor molecule for several lipids with central roles in signaling, for example lysophosphatidic acid (LPA), phosphatidic acid (PA) and diacylglycerol (DAG). LPA activates intracellular signaling pathways by binding to specific LPA receptors, including membrane-bound G protein-coupled receptors and the intracellular nuclear receptor, PPARγ. Conversely, PA and DAG mediate signaling by acting as lipid anchors that bind and activate several signaling proteins. For example, binding of GTPases and PKC to PA and DAG, respectively, increases the activation of signaling networks, mediating processes such as migration, adhesion, proliferation or anti-apoptosis—all relevant for tumor development. We present a concept by which EDI3 either directly generates signaling molecules or provides “membrane anchors” for downstream signaling factors. As a result, EDI3 links choline metabolism to signaling activities resulting in a more malignant phenotype. PMID:23114620

  14. Release of neuronal HMGB1 by ethanol through decreased HDAC activity activates brain neuroimmune signaling.

    PubMed

    Zou, Jian Y; Crews, Fulton T

    2014-01-01

    Neuroimmune gene induction is involved in many brain pathologies including addiction. Although increased expression of proinflammatory cytokines has been found in ethanol-treated mouse brain and rat brain slice cultures as well as in post-mortem human alcoholic brain, the mechanisms remain elusive. High-mobility group box 1 (HMGB1) protein is a nuclear protein that has endogenous cytokine-like activity. We previously found increased HMGB1 in post-mortem alcoholic human brain as well as in ethanol treated mice and rat brain slice cultures. The present study investigated the mechanisms for ethanol-induced release of HMGB1 and neuroimmune activation in a model of rat hippocampal-entorhinal cortex (HEC) brain slice cultures. Ethanol exposure triggered dose-dependent HMGB1 release, predominantly from neuronal cells. Inhibitors of histone deacetylases (HDACs) promoted nucleocytoplasmic mobilization of HDAC1/4 and HMGB1 resulting in increased total HMGB1 and acetylated HMGB1 release. Similarly, ethanol treatment was found to induce the translocation of HDAC1/4 and HMGB1 proteins from nuclear to cytosolic fractions. Furthermore, ethanol treatment reduced HDAC1/4 mRNA and increased acetylated HMGB1 release into the media. These results suggest decreased HDAC activity may be critical in regulating acetylated HMGB1 release from neurons in response to ethanol. Ethanol and HMGB1 treatment increased mRNA expression of proinflammatory cytokines TNFα and IL-1β as well as toll-like receptor 4 (TLR4). Targeting HMGB1 or microglial TLR4 by using siRNAs to HMGB1 and TLR4, HMGB1 neutralizing antibody, HMGB1 inhibitor glycyrrhizin and TLR4 antagonist as well as inhibitor of microglial activation all blocked ethanol-induced expression of proinflammatory cytokines TNFα and IL-1β. These results support the hypothesis that ethanol alters HDACs that regulate HMGB1 release and that danger signal HMGB1 as endogenous ligand for TLR4 mediates ethanol-induced brain neuroimmune signaling

  15. Ethanol activates midkine and anaplastic lymphoma kinase signaling in neuroblastoma cells and in the brain.

    PubMed

    He, Donghong; Chen, Hu; Muramatsu, Hisako; Lasek, Amy W

    2015-11-01

    Alcohol engages signaling pathways in the brain. Midkine (MDK) is a neurotrophic factor that is over-expressed in the prefrontal cortex of alcoholics. MDK and one of its receptors, anaplastic lymphoma kinase (ALK), also regulate behavioral responses to ethanol in mice. The goal of this study was to determine whether MDK and ALK expression and signaling are activated by ethanol. We found that ethanol treatment of neuroblastoma cells increased MDK and ALK expression. We also assessed activation of ALK by ethanol in cells and found that ALK and ALK-dependent extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 (STAT3) phosphorylation increased rapidly with ethanol exposure. Similarly, treatment of cells with recombinant MDK protein increased ALK, ERK and STAT3 phosphorylation, suggesting that ethanol may utilize MDK to activate ALK signaling. In support of this, transfection of cells with MDK siRNAs attenuated ALK signaling in response to ethanol. Ethanol also activates ERK signaling in the brain. We found that inhibition of ALK or knockout of MDK attenuated ethanol-induced ERK phosphorylation in mouse amygdala. These results demonstrate that ethanol engages MDK and ALK signaling, which has important consequences for alcohol-induced neurotoxicity and the regulation of behaviors related to alcohol abuse.

  16. Early induction of CREB activation and CREB-regulating signalling by antidepressants.

    PubMed

    Tardito, Daniela; Musazzi, Laura; Tiraboschi, Ettore; Mallei, Alessandra; Racagni, Giorgio; Popoli, Maurizio

    2009-11-01

    Converging evidence points to adaptive changes in neuroplasticity and gene expression as mediators of therapeutic action of antidepressants. Activation of cAMP response-element binding protein (CREB) and CREB-regulating signalling are considered main effectors in these mechanisms. We analysed the temporal profile of intracellular changes induced by antidepressants, by measuring activation of major CREB-regulating signalling cascades and activation (Ser133 phosphorylation) of CREB. The main aims of the study were to investigate how these different variables are modulated with time, whether stronger activation of signalling cascades corresponds to stronger activation of CREB, and whether these changes are different in distinct brain areas. Rat groups were treated for 1, 2 or 3 wk with the antidepressants fluoxetine or reboxetine; in additional groups drug treatment was followed by a washout week (3+1). Activation of CREB and major effectors in signalling cascades were analysed by Western blot analysis with phospho-antibodies, in nuclear and cytosolic fractions from hippocampus and prefrontal/frontal cortex (P/FC). Surprisingly, CREB activation was already maximal after 1-wk treatment. In hippocampus early and stronger CREB activation was consistent with early and stronger activation of signalling. For both drugs, the profile of activation in P/FC was different from that observed in hippocampus. The results also showed that, contrary to the activatory role of MAP-ERKs and CaM kinase IV, nuclear alphaCaM kinase II was inactivated in parallel with activation of CREB.

  17. Arginine vasotocin activates phosphoinositide signal transduction system and potentiates N-acetyltransferase activity in the rat pineal gland.

    PubMed

    Novotná, R; Jác, M; Hájek, I; Novotný, I

    1999-03-05

    The pineal gland is innervated by pinealopetal peptidergic fibers originating in the hypothalamic nuclei which release arginine vasopressin (AVP) and arginine vasotocin (AVT) from their endings. Since the mechanism of AVT action on the pineal signal transduction and melatonin synthesis has not been determined so far, we examined the effect of AVT on the phosphoinositide signalling system and the N-acetyltransferase (NAT) activity in the rat pineal gland. The effect of AVP 4-9 fragment and AVP analogue desmopressin was also tested. The phosphoinositide signalling system was studied by measuring 32P labelling of phosphatidylinositol (PI), phosphatidylinositol phosphate (PIP) and phosphatidylinositol bisphosphate (PIP2) which reflects PI cycle activation. AVT (10(-5) and 10(-4) M) induced a significant increase in 32P labelling of PI, PIP and PIP2. The AVT mediated activation of the PI signal cascade was supressed by the vasopressin V1 receptor antagonist. The desmopressin and AVP 4-9 fragment were without the effect on PI signalling. To assess the AVT role in the melatonin synthesis we studied the daily pattern of the pineal NAT activity in rats treated by AVT (10 microg/100 g b.w). AVT application in the dark period of the day significantly increased nocturnal NAT activity. It can be summarized that AVT activates PI signalling system and potentiates NAT activity in the rat pineal gland.

  18. Alternative splicing of MALT1 controls signalling and activation of CD4(+) T cells.

    PubMed

    Meininger, Isabel; Griesbach, Richard A; Hu, Desheng; Gehring, Torben; Seeholzer, Thomas; Bertossi, Arianna; Kranich, Jan; Oeckinghaus, Andrea; Eitelhuber, Andrea C; Greczmiel, Ute; Gewies, Andreas; Schmidt-Supprian, Marc; Ruland, Jürgen; Brocker, Thomas; Heissmeyer, Vigo; Heyd, Florian; Krappmann, Daniel

    2016-04-12

    MALT1 channels proximal T-cell receptor (TCR) signalling to downstream signalling pathways. With MALT1A and MALT1B two conserved splice variants exist and we demonstrate here that MALT1 alternative splicing supports optimal T-cell activation. Inclusion of exon7 in MALT1A facilitates the recruitment of TRAF6, which augments MALT1 scaffolding function, but not protease activity. Naive CD4(+) T cells express almost exclusively MALT1B and MALT1A expression is induced by TCR stimulation. We identify hnRNP U as a suppressor of exon7 inclusion. Whereas selective depletion of MALT1A impairs T-cell signalling and activation, downregulation of hnRNP U enhances MALT1A expression and T-cell activation. Thus, TCR-induced alternative splicing augments MALT1 scaffolding to enhance downstream signalling and to promote optimal T-cell activation.

  19. Alternative splicing of MALT1 controls signalling and activation of CD4+ T cells

    PubMed Central

    Meininger, Isabel; Griesbach, Richard A.; Hu, Desheng; Gehring, Torben; Seeholzer, Thomas; Bertossi, Arianna; Kranich, Jan; Oeckinghaus, Andrea; Eitelhuber, Andrea C.; Greczmiel, Ute; Gewies, Andreas; Schmidt-Supprian, Marc; Ruland, Jürgen; Brocker, Thomas; Heissmeyer, Vigo; Heyd, Florian; Krappmann, Daniel

    2016-01-01

    MALT1 channels proximal T-cell receptor (TCR) signalling to downstream signalling pathways. With MALT1A and MALT1B two conserved splice variants exist and we demonstrate here that MALT1 alternative splicing supports optimal T-cell activation. Inclusion of exon7 in MALT1A facilitates the recruitment of TRAF6, which augments MALT1 scaffolding function, but not protease activity. Naive CD4+ T cells express almost exclusively MALT1B and MALT1A expression is induced by TCR stimulation. We identify hnRNP U as a suppressor of exon7 inclusion. Whereas selective depletion of MALT1A impairs T-cell signalling and activation, downregulation of hnRNP U enhances MALT1A expression and T-cell activation. Thus, TCR-induced alternative splicing augments MALT1 scaffolding to enhance downstream signalling and to promote optimal T-cell activation. PMID:27068814

  20. Asphyxia-activated corticocardiac signaling accelerates onset of cardiac arrest

    PubMed Central

    Li, Duan; Mabrouk, Omar S.; Liu, Tiecheng; Tian, Fangyun; Xu, Gang; Rengifo, Santiago; Choi, Sarah J.; Mathur, Abhay; Crooks, Charles P.; Kennedy, Robert T.; Wang, Michael M.; Ghanbari, Hamid; Borjigin, Jimo

    2015-01-01

    The mechanism by which the healthy heart and brain die rapidly in the absence of oxygen is not well understood. We performed continuous electrocardiography and electroencephalography in rats undergoing experimental asphyxia and analyzed cortical release of core neurotransmitters, changes in brain and heart electrical activity, and brain–heart connectivity. Asphyxia stimulates a robust and sustained increase of functional and effective cortical connectivity, an immediate increase in cortical release of a large set of neurotransmitters, and a delayed activation of corticocardiac functional and effective connectivity that persists until the onset of ventricular fibrillation. Blocking the brain’s autonomic outflow significantly delayed terminal ventricular fibrillation and lengthened the duration of detectable cortical activities despite the continued absence of oxygen. These results demonstrate that asphyxia activates a brainstorm, which accelerates premature death of the heart and the brain. PMID:25848007

  1. Pleiotropic patterning response to activation of Shh signaling in the limb apical ectodermal ridge.

    PubMed

    Wang, Chi-Kuang Leo; Tsugane, Mizuyo H; Scranton, Victoria; Kosher, Robert A; Pierro, Louis J; Upholt, William B; Dealy, Caroline N

    2011-05-01

    Sonic hedgehog (Shh) signaling in the limb plays a central role in coordination of limb patterning and outgrowth. Shh expression in the limb is limited to the cells of the zone of polarizing activity (ZPA), located in posterior limb bud mesoderm. Shh is not expressed by limb ectoderm or apical ectodermal ridge (AER), but recent studies suggest a role for AER-Shh signaling in limb patterning. Here, we have examined the effects of activation of Shh signaling in the AER. We find that targeted expression of Shh in the AER activates constitutive Shh signaling throughout the AER and subjacent limb mesoderm, and causes a range of limb patterning defects with progressive severity from mild polydactyly, to polysyndactyly with proximal defects, to severe oligodactyly with phocomelia and partial limb ventralization. Our studies emphasize the importance of control of the timing, level and location of Shh pathway signaling for limb anterior-posterior, proximal-distal, and dorsal-ventral patterning.

  2. Pleiotropic patterning response to activation of Shh signaling in the limb Apical Ectodermal Ridge

    PubMed Central

    Wang, Chi-Kuang Leo; Tsugane, Mizuyo H.; Scranton, Victoria; Kosher, Robert A.; Pierro, Louis J.; Upholt, William B.; Dealy, Caroline N.

    2012-01-01

    Sonic hedgehog (Shh) signaling in the limb plays a central role in coordination of limb patterning and outgrowth. Shh expression in the limb is limited to the cells of the Zone of Polarizing Activity (ZPA), located in posterior limb bud mesoderm. Shh is not expressed by limb ectoderm or AER, but recent studies suggest a role for AER-Shh signaling in limb patterning. Here, we have examined the effects of activation of Shh signaling in the AER. We find that targeted expression of Shh in the AER activates constitutive Shh signaling throughout the AER and subjacent limb mesoderm, and causes a range of limb patterning defects with progressive severity from mild polydactyly, to polysyndactyly with proximal defects, to severe oligodactyly with phocomelia and partial limb ventralization. Our studies emphasize the importance of control of the timing, level and location of Shh pathway signaling for limb AP, PD and DV patterning. PMID:21465622

  3. GPCR-like signaling mediated by smoothened contributes to acquired chemoresistance through activating Gli

    PubMed Central

    2014-01-01

    Background Smoothened (Smo), which possesses a structural similarity with classic G-protein coupled receptors (GPCR), is the most important molecular target in Hedgehog (Hh) signaling system for developing anticancer drugs; however, whether Smo may transmit GPCR-like signaling to activate the canonical transcriptional factor Gli of Hh signaling system and consequently to be involved in the Gli-dependent biological events remains controversial. Results In this study, using the acquired chemoresistant cancer cell lines and their respective parental cells, we found that Smo may activate Gli through Gαi, Gβγ-JNK signaling axis, thereby promoting the Gli-dependent acquired chemoresistance. These observations were further complementarily strengthened by data obtained from chemosensitive cancer cells with artificially elevated Hh pathway activity. Conclusions Hence, our data demonstrate that GPCR-like signaling mediated by Smo contributes to the acquired chemoresistance through activating the canonical Hh transcriptional factor Gli; therefore improving our knowledge of the nature of the signal transduction of Smo and the molecular mechanisms responsible for the acquired chemoresistance maintained by Hh pathway. Moreover, our data that JNK after activated by Smo-Gβγ signaling axis may stimulate the Gli activity and consequently promotes acquired chemoresistance expose a promising and potential target for developing anti-cancer drugs aimed at Hh pathway and for combating the acquired resistance raised by using of anti-cancer drugs targeting Smo. PMID:24393163

  4. Signal transduction-associated and cell activation-linked antigens expressed in human mast cells.

    PubMed

    Valent, Peter; Ghannadan, Minoo; Hauswirth, Alexander W; Schernthaner, Gerit-Holger; Sperr, Wolfgang R; Arock, Michel

    2002-05-01

    Mast cells (MCs) are multifunctional hematopoietic effector cells that produce and release an array of biologically active mediator substances. Growth and functions of MCs are regulated by cytokines, other extracellular factors, surface and cytoplasmic receptors, oncogene products, and a complex network of signal transduction cascades. Key regulators of differentiation of MCs appear to be stem cell factor (SCF) and its tyrosine kinase receptor KIT (c-kit proto-oncogene product=CD117), downstream-acting elements, and the mi transcription factor (MITF). Signaling through KIT is negatively regulated by the signal regulatory protein (SIRP)-alpha (CD172a)-SHP-1-pathway that is disrupted in neoplastic MCs in MC proliferative disorders. Both KIT and FcepsilonRI are involved in MC activation and mediator release. Activation of MCs through FcepsilonRI is associated with increased expression of activation-linked membrane antigens as well as with signaling events involving Lyn and Syk kinases, the phosphatidylinositol-3-kinase-pathway, Ras pathway, and the phospholipase C-protein kinase C pathway. A similar network of signaling is found in SCF-activated MCs. The current article gives an overview on signal transduction-associated and activation-linked antigens expressed in human MCs. Wherever possible the functional implication of signaling pathways and antigen expression are discussed.

  5. Shuttle extravehicular activity signal processor pulse amplitude modulation decommutator

    NASA Technical Reports Server (NTRS)

    Noble, D. E.; Conrad, W. M.

    1974-01-01

    To provide data with long-term stability and accuracy, the pulse amplitude modulation (PAM) decommutator was synchronized to the PAM-return to zero wavetrain, and each channel was sampled with a common sample and hold circuit and digitized sequentially. The digital value of each channel was then scaled by the digital value of the calibration channels. The corrected digital value of each channel was stored for one complete frame and then transferred to the multiplexer-demultiplexer at a high rate in one block of serial digital data. A test model was built to demonstrate this design approach taken for the PAM decom and performance data was provided. The accuracies obtained with various signal to noise ratios are shown.

  6. Fluctuation analysis of activity biosensor images for the study of information flow in signaling pathways.

    PubMed

    Vilela, Marco; Halidi, Nadia; Besson, Sebastien; Elliott, Hunter; Hahn, Klaus; Tytell, Jessica; Danuser, Gaudenz

    2013-01-01

    Comprehensive understanding of cellular signal transduction requires accurate measurement of the information flow in molecular pathways. In the past, information flow has been inferred primarily from genetic or protein-protein interactions. Although useful for overall signaling, these approaches are limited in that they typically average over populations of cells. Single-cell data of signaling states are emerging, but these data are usually snapshots of a particular time point or limited to averaging over a whole cell. However, many signaling pathways are activated only transiently in specific subcellular regions. Protein activity biosensors allow measurement of the spatiotemporal activation of signaling molecules in living cells. These data contain highly complex, dynamic information that can be parsed out in time and space and compared with other signaling events as well as changes in cell structure and morphology. We describe in this chapter the use of computational tools to correct, extract, and process information from time-lapse images of biosensors. These computational tools allow one to explore the biosensor signals in a multiplexed approach in order to reconstruct the sequence of signaling events and consequently the topology of the underlying pathway. The extraction of this information, dynamics and topology, provides insight into how the inputs of a signaling network are translated into its biochemical or mechanical outputs.

  7. 3D Chirp Sonar Images on Fluid Migration Pathways and Their Implications on Seafloor Stability East of the Fangliao Submarine Canyon Offshore SW Taiwan

    NASA Astrophysics Data System (ADS)

    Lu, Y. W.; Liu, C. S.; Su, C. C.; Hsu, H. H.; Chen, Y. H.

    2015-12-01

    This study utilizes both chirp sonar images and coring results to investigate the unstable seafloor strata east of the Fangliao Submarine Canyon offshore southwestern Taiwan. We have constructed 3D chirp sonar images from a densely surveyed block to trace the attitude of an acoustic transparent layer and features caused by fluid activities. Based on the distribution of this transparent layer and fluid-related features, we suggest that this transparent layer forms a pathway for fluid migration which induces fluid-related characters such as acoustic blanking and fluid chimneys in the 3D chirp sonar images. Cored seafloor samples are used in this study to investigate the sediment compositions. The 210Pb activity profiles of the cores show oscillating and unsteady values at about 20~25 cm from core top. The bulk densities of the core samples in the same section (about 20~25 cm from core top) give values lower than those at deeper parts of the cores. These results indicate that the water content is much higher in the shallow sediments than in the deeper strata. From core sample analyses, we deduce that the local sediments are disturbed by liquefaction. From the analyses of 3D chirp sonar images and core data, we suggest that the seafloor east of the Fangliao Submarine Canyon is in an unstable condition, if disturbed by earthquakes, submarine landslides and gravity flows could be easily triggered and cause some geohazards, like breaking submarine cables during the 2006 Pingtung earthquake event.

  8. Mapping Neuronal Activation and the Influence of Adrenergic Signaling during Contextual Memory Retrieval

    ERIC Educational Resources Information Center

    Zhang, Wei-Ping; Guzowski, John F.; Thomas, Steven A.

    2005-01-01

    We recently described a critical role for adrenergic signaling in the hippocampus during contextual and spatial memory retrieval. To determine which neurons are activated by contextual memory retrieval and its sequelae in the presence and absence of adrenergic signaling, transcriptional imaging for the immediate-early gene "Arc" was used in…

  9. 78 FR 28801 - Foreign-Trade Zone 117-Orange, TX, Authorization of Production Activity, Signal International...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-16

    ... Foreign-Trade Zones Board Foreign-Trade Zone 117--Orange, TX, Authorization of Production Activity, Signal International Texas GP, LLC (Shipbuilding), Orange, TX On January 10, 2013, the Foreign Trade Zone of Southeast...-Trade Zones (FTZ) Board on behalf of Signal International Texas GP, LLC, in Orange, Texas....

  10. Neuronal activity regulates remyelination via glutamate signalling to oligodendrocyte progenitors

    PubMed Central

    Gautier, Hélène O. B.; Evans, Kimberley A.; Volbracht, Katrin; James, Rachel; Sitnikov, Sergey; Lundgaard, Iben; James, Fiona; Lao-Peregrin, Cristina; Reynolds, Richard; Franklin, Robin J. M.; Káradóttir, Ragnhildur T

    2015-01-01

    Myelin regeneration can occur spontaneously in demyelinating diseases such as multiple sclerosis (MS). However, the underlying mechanisms and causes of its frequent failure remain incompletely understood. Here we show, using an in-vivo remyelination model, that demyelinated axons are electrically active and generate de novo synapses with recruited oligodendrocyte progenitor cells (OPCs), which, early after lesion induction, sense neuronal activity by expressing AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)/kainate receptors. Blocking neuronal activity, axonal vesicular release or AMPA receptors in demyelinated lesions results in reduced remyelination. In the absence of neuronal activity there is a ∼6-fold increase in OPC number within the lesions and a reduced proportion of differentiated oligodendrocytes. These findings reveal that neuronal activity and release of glutamate instruct OPCs to differentiate into new myelinating oligodendrocytes that recover lost function. Co-localization of OPCs with the presynaptic protein VGluT2 in MS lesions implies that this mechanism may provide novel targets to therapeutically enhance remyelination. PMID:26439639

  11. Effect of broadband-noise masking on the behavioral response of a harbor porpoise (Phocoena phocoena) to 1-s duration 6-7 kHz sonar up-sweeps.

    PubMed

    Kastelein, Ronald A; Steen, Nele; de Jong, Christ; Wensveen, Paul J; Verboom, Willem C

    2011-04-01

    Naval sonar systems produce signals which may affect the behavior of harbor porpoises, though their effect may be reduced by ambient noise. To show how natural ambient noise influences the effect of sonar sweeps on porpoises, a porpoise in a pool was exposed to 1-s duration up-sweeps, similar in frequency range (6-7 kHz) to those of existing naval sonar systems. The sweep signals had randomly generated sweep intervals of 3-7 s (duty cycle: 19%). Behavioral parameters during exposure to signals were compared to those during baseline periods. The sessions were conducted under five background noise conditions: the local normal ambient noise and four conditions mimicking the spectra for wind-generated noise at Sea States 2-8. In all conditions, the sweeps caused the porpoise to swim further away from the transducer, surface more often, swim faster, and breathe more forcefully than during the baseline periods. However, the higher the background noise level, the smaller the effects of the sweeps on the surfacing behavior of the porpoise. Therefore, the effects of naval sonar systems on harbor porpoises are determined not only by the received level of the signals and the hearing sensitivity of the animals but also by the background noise.

  12. Queen signals in a stingless bee: suppression of worker ovary activation and spatial distribution of active compounds

    PubMed Central

    Nunes, Túlio M.; Mateus, Sidnei; Favaris, Arodi P.; Amaral, Mônica F. Z. J.; von Zuben, Lucas G.; Clososki, Giuliano C.; Bento, José M. S.; Oldroyd, Benjamin P.; Silva, Ricardo; Zucchi, Ronaldo; Silva, Denise B.; Lopes, Norberto P.

    2014-01-01

    In most species of social insect the queen signals her presence to her workers via pheromones. Worker responses to queen pheromones include retinue formation around the queen, inhibition of queen cell production and suppression of worker ovary activation. Here we show that the queen signal of the Brazilian stingless bee Friesella schrottkyi is a mixture of cuticular hydrocarbons. Stingless bees are therefore similar to ants, wasps and bumble bees, but differ from honey bees in which the queen's signal mostly comprises volatile compounds originating from the mandibular glands. This shows that cuticular hydrocarbons have independently evolved as the queen's signal across multiple taxa, and that the honey bees are exceptional. We also report the distribution of four active queen-signal compounds by Matrix-assisted laser desorption/ionization (MALDI) imaging. The results indicate a relationship between the behavior of workers towards the queen and the likely site of secretion of the queen's pheromones. PMID:25502598

  13. Tumor-secreted LOXL2 Activates Fibroblasts Through FAK Signaling

    PubMed Central

    Barker, Holly E.; Bird, Demelza; Lang, Georgina; Erler, Janine T.

    2013-01-01

    Cancer-associated fibroblasts enhance cancer progression when activated by tumor cells through mechanisms not yet fully understood. Blocking mammary tumor cell-derived lysyl oxidase-like 2 (LOXL2) significantly inhibited mammary tumor cell invasion and metastasis in transgenic and orthotopic mouse models. Here we discovered that tumor-derived LOXL2 directly activated stromal fibroblasts in the tumor microenvironment. Genetic manipulation or antibody inhibition of LOXL2 in orthotopically grown mammary tumors reduced the expression of α-smooth muscle actin (α-SMA). Using a marker for reticular fibroblasts, it was determined that expression of α-SMA was localized to fibroblasts recruited from the host tissue. This marker also revealed that the matrix present in tumors with reduced levels of LOXL2 was more scattered compared to control tumors which exhibited matrices with dense, parallel alignments. Importantly, in vitro assays revealed that tumor-derived LOXL2 and a recombinant LOXL2 protein induced fibroblast branching on collagen matrices, as well as increased fibroblast-mediated collagen contraction and invasion of fibroblasts through extracellular matrix (ECM). Moreover, LOXL2 induced the expression of α-SMA in fibroblasts grown on collagen matrices. Mechanistically, it was determined that LOXL2 activated fibroblasts through integrin-mediated FAK activation. These results indicate that inhibition of LOXL2 in tumors not only reduces tumor cell invasion but also attenuates the activation of host cells in the tumor microenvironment. Implications: These findings reveal new insight into the mechanisms of fibroblast activation, a novel function of LOXL2, and further highlight the importance of generating LOXL2-targeted therapies for the prevention of tumor progression and metastasis. PMID:24008674

  14. EGF stimulates the activation of EGF receptors and the selective activation of major signaling pathways during mitosis.

    PubMed

    Wee, Ping; Shi, Huaiping; Jiang, Jennifer; Wang, Yuluan; Wang, Zhixiang

    2015-03-01

    Mitosis and epidermal growth factor (EGF) receptor (EGFR) are both targets for cancer therapy. The role of EGFR signaling in mitosis has been rarely studied and poorly understood. The limited studies indicate that the activation of EGFR and downstream signaling pathways is mostly inhibited during mitosis. However, we recently showed that EGFR is phosphorylated in response to EGF stimulation in mitosis. Here we studied EGF-induced EGFR activation and the activation of major signaling pathways downstream of EGFR during mitosis. We showed that EGFR was strongly activated by EGF during mitosis as all the five major tyrosine residues including Y992, Y1045, Y1068, Y1086, and Y1173 were phosphorylated to a level similar to that in the interphase. We further showed that the activated EGFR is able to selectively activate some downstream signaling pathways while avoiding others. Activated EGFR is able to activate PI3K and AKT2, but not AKT1, which may be responsible for the observed effects of EGF against nocodazole-induced cell death. Activated EGFR is also able to activate c-Src, c-Cbl and PLC-γ1 during mitosis. However, activated EGFR is unable to activate ERK1/2 and their downstream substrates RSK and Elk-1. While it activated Ras, EGFR failed to fully activate Raf-1 in mitosis due to the lack of phosphorylation at Y341 and the lack of dephosphorylation at pS259. We conclude that contrary to the dogma, EGFR is activated by EGF during mitosis. Moreover, EGFR-mediated cell signaling is regulated differently from the interphase to specifically serve the needs of the cell in mitosis.

  15. Prototype Task Network Model to Simulate the Analysis of Narrow Band Sonar Data and the Effects of Automation on Critical Operator Tasks

    DTIC Science & Technology

    2016-06-07

    task of building the underwater maritime picture depends heavily on the accurate and timely analysis of sonar acoustic data that may be highly...uncertain in origin and embedded in background “noise” from a variety of underwater acoustic sources. The task of distinguishing signal from noise and...time course of many contacts is sufficiently slow, which, in itself, does not produce time stress upon operators, the large volume of acoustic data

  16. Activated signal transducers and activators of transcription 3 signaling induces CD46 expression and protects human cancer cells from complement-dependent cytotoxicity.

    PubMed

    Buettner, Ralf; Huang, Mei; Gritsko, Tanya; Karras, Jim; Enkemann, Steve; Mesa, Tania; Nam, Sangkil; Yu, Hua; Jove, Richard

    2007-08-01

    CD46 is one of the complement-regulatory proteins expressed on the surface of normal and tumor cells for protection against complement-dependent cytotoxicity. Cancer cells need to access the blood circulation for continued growth and metastasis, thus exposing themselves to destruction by complement system components. Previous studies have established that the signal transducers and activators of transcription 3 (STAT3) transcription factor is persistently activated in a wide variety of human cancer cells and primary tumor tissues compared with their normal counterparts. Using microarray gene expression profiling, we identified the CD46 gene as a target for activated STAT3 signaling in human breast and prostate cancer cells. The CD46 promoter contains two binding sites for activated STAT3 and mutations introduced into the major site abolished STAT3 binding. Chromatin immunoprecipitation confirms binding of STAT3 to the CD46 promoter. CD46 promoter activity is induced by activation of STAT3 and blocked by a dominant-negative form of STAT3 in luciferase reporter assays. CD46 mRNA expression is induced by interleukin-6 and by transient transfection of normal human epithelial cells with a persistently active mutant construct of STAT3, STAT3C. Furthermore, we show that inhibition of STAT3-mediated CD46 cell surface expression sensitizes DU145 prostate cancer cells to cytotoxicity in an in vitro complement lysis assay using rabbit anti-DU145 antiserum and rabbit complement. These results show that activated STAT3 signaling induces the CD46 promoter and protects human cancer cells from complement-dependent cytotoxicity, suggesting a potential mechanism whereby oncogenic signaling contributes to tumor cell evasion of antibody-mediated immunity.

  17. Sorafenib inhibits signal transducer and activator of transcription 3 signaling associated with growth arrest and apoptosis of medulloblastomas.

    PubMed

    Yang, Fan; Van Meter, Timothy E; Buettner, Ralf; Hedvat, Michael; Liang, Wei; Kowolik, Claudia M; Mepani, Nilesh; Mirosevich, Janni; Nam, Sangkil; Chen, Mike Y; Tye, Gary; Kirschbaum, Mark; Jove, Richard

    2008-11-01

    Medulloblastomas are the most frequent malignant brain tumors in children. Sorafenib (Nexavar, BAY43-9006), a multikinase inhibitor, blocks cell proliferation and induces apoptosis in a variety of tumor cells. Sorafenib inhibited proliferation and induced apoptosis in two established cell lines (Daoy and D283) and a primary culture (VC312) of human medulloblastomas. In addition, sorafenib inhibited phosphorylation of signal transducer and activator of transcription 3 (STAT3) in both cell lines and primary tumor cells. The inhibition of phosphorylated STAT3 (Tyr(705)) occurs in a dose- and time-dependent manner. In contrast, AKT (protein kinase B) was only decreased in D283 and VC312 medulloblastoma cells and mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2) were not inhibited by sorafenib in these cells. Both D-type cyclins (D1, D2, and D3) and E-type cyclin were down-regulated by sorafenib. Also, expression of the antiapoptotic protein Mcl-1, a member of the Bcl-2 family, was decreased and correlated with apoptosis induced by sorafenib. Finally, sorafenib suppressed the growth of human medulloblastoma cells in a mouse xenograft model. Together, our data show that sorafenib blocks STAT3 signaling as well as expression of cell cycle and apoptosis regulatory proteins, associated with inhibition of cell proliferation and induction of apoptosis in medulloblastomas. These findings provide a rationale for treatment of pediatric medulloblastomas with sorafenib.

  18. Danger signals activating innate immunity in graft-versus-host disease.

    PubMed

    Zeiser, Robert; Penack, Olaf; Holler, Ernst; Idzko, Marco

    2011-09-01

    Extensive cell death with consecutive release of danger signals can cause immune-mediated tissue destruction. The abundance of cell death is likely to determine the relevance of the danger signals as physiological mechanisms that counteract immune activation may be overruled. Such constellation is conceivable in chemo-/radiotherapy-induced tissue damage, reperfusion injury, trauma, and severe infection. Studies on graft-versus-host disease (GvHD) development have to consider the effects of chemo-/radiotherapy-related tissue damage leading to the release of exogenous and endogenous danger signals. Our previous work has demonstrated a role for adenosine-5'-triphosphate (ATP) as an endogenous danger signal in GvHD. Besides ATP, uric acid or soluble extracellular matrix components are functional danger signals that activate the NLRP3 inflammasome when released from dying cells or from extracellular matrix. In contrast to sterile inflammation, GvHD is more complex since bacterial components that leak through damaged intestinal barriers and the skin can activate pattern recognition receptors and directly contribute to GvHD pathogenesis. These exogenous danger signals transmit immune activation via toll-like receptors and NOD-like receptors of the innate immune system. This review covers both the impact of endogenous and exogenous danger signals activating innate immunity in GvHD.

  19. Lymphocyte signaling and activation by the CARMA1-BCL10-MALT1 signalosome.

    PubMed

    Meininger, Isabel; Krappmann, Daniel

    2016-12-01

    The CARMA1-BCL10-MALT1 (CBM) signalosome triggers canonical NF-κB signaling and lymphocyte activation upon antigen-receptor stimulation. Genetic studies in mice and the analysis of human immune pathologies unveiled a critical role of the CBM complex in adaptive immune responses. Great progress has been made in elucidating the fundamental mechanisms that dictate CBM assembly and disassembly. By bridging proximal antigen-receptor signaling to downstream signaling pathways, the CBM complex exerts a crucial scaffolding function. Moreover, the MALT1 subunit confers a unique proteolytic activity that is key for lymphocyte activation. Deregulated 'chronic' CBM signaling drives constitutive NF-κB signaling and MALT1 activation, which contribute to the development of autoimmune and inflammatory diseases as well as lymphomagenesis. Thus, the processes that govern CBM activation and function are promising targets for the treatment of immune disorders. Here, we summarize the current knowledge on the functions and mechanisms of CBM signaling in lymphocytes and how CBM deregulations contribute to aberrant signaling in malignant lymphomas.

  20. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    SciTech Connect

    Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C.; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.

    2011-10-14

    Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  1. Ubiquitination in Signaling to and Activation of IKK

    PubMed Central

    Chen, Zhijian J.

    2013-01-01

    A role of polyubiquitination in the activation of IκB kinase (IKK) through a proteasome-independent mechanism was first reported in 1996, but the physiological significance of this finding was not clear until 2000 when TRAF6 was found to be a ubiquitin E3 ligase that catalyzes lysine-63 (K63) polyubiquitination. Since then, several proteins known to regulate IKK have been linked to the ubiquitin pathway. These include the deubiquitination enzymes CYLD and A20 that inhibit IKK, and the ubiquitin binding proteins NEMO and TAB2 which are the regulatory subunits of IKK and TAK1 kinase complexes, respectively. Now accumulating evidence strongly supports a central role of K63 polyubiquitination in IKK activation by multiple immune and inflammatory pathways. Interestingly, recent research suggests that some alternative ubiquitin chains such as linear or K11 ubiquitin chains may also play a role in certain pathways such as the TNF pathway. Here I present a historical narrative of the discovery of the role of ubiquitin in IKK activation, review recent advances in understanding the role and mechanism of ubiquitin-mediated IKK activation, and raise some questions to be resolved in future research. PMID:22435549

  2. Quantifying Fish Backscattering using SONAR Instrument and Kirchhoff Ray Mode (KRM) Model

    NASA Astrophysics Data System (ADS)

    Manik, Henry M.

    2016-08-01

    Sonar instrument was used to study backscattering from tuna fish. Extraction of target strength, incidence angle, and frequency dependence of the backscattered signal for individual scatterer was important for biological information. For this purpose, acoustic measurement of fish backscatter was conducted in the laboratory. Characteristics and general trends of the target strength of fish with special reference to tuna fish were investigated by using a Kirchhoff Ray Mode (KRM) model. Backscattering strength were calculated for the KRM having typical morphological and physical parameters of actual fish. Those backscattering amplitudes were shown as frequency, body length, backscattering patterns, the density and sound speed dependences, and orientation dependence. These results were compared with experimentally measured target strength data and good agreement was found. Measurement and model showed the target strength from the fish are depend on the presence of swimbladder. Target Strength increase with increasing the frequency and fish length.

  3. Towards brain-activity-controlled information retrieval: Decoding image relevance from MEG signals.

    PubMed

    Kauppi, Jukka-Pekka; Kandemir, Melih; Saarinen, Veli-Matti; Hirvenkari, Lotta; Parkkonen, Lauri; Klami, Arto; Hari, Riitta; Kaski, Samuel

    2015-05-15

    We hypothesize that brain activity can be used to control future information retrieval systems. To this end, we conducted a feasibility study on predicting the relevance of visual objects from brain activity. We analyze both magnetoencephalographic (MEG) and gaze signals from nine subjects who were viewing image collages, a subset of which was relevant to a predetermined task. We report three findings: i) the relevance of an image a subject looks at can be decoded from MEG signals with performance significantly better than chance, ii) fusion of gaze-based and MEG-based classifiers significantly improves the prediction performance compared to using either signal alone, and iii) non-linear classification of the MEG signals using Gaussian process classifiers outperforms linear classification. These findings break new ground for building brain-activity-based interactive image retrieval systems, as well as for systems utilizing feedback both from brain activity and eye movements.

  4. ASBESTOS-INDUCED ACTIVATION OF CELL SIGNALING PATHWAYS IN HUMAN BRONCHIAL EPITHELIAL CELLS

    EPA Science Inventory

    Using respiratory epithelial cells transfected with either superoxide dismutase (SOD) or catalase, the authors tested the hypothesis that the activation of the epidermal growth factor (EGF) receptor signal pathway after asbestos exposure involves an oxidative stress. Western blot...

  5. Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways.

    PubMed

    Huang, Shurong; Rutkowsky, Jennifer M; Snodgrass, Ryan G; Ono-Moore, Kikumi D; Schneider, Dina A; Newman, John W; Adams, Sean H; Hwang, Daniel H

    2012-09-01

    Toll-like receptor 4 (TLR4) and TLR2 were shown to be activated by saturated fatty acids (SFAs) but inhibited by docosahexaenoic acid (DHA). However, one report suggested that SFA-induced TLR activation in cell culture systems is due to contaminants in BSA used for solubilizing fatty acids. This report raised doubt about proinflammatory effects of SFAs. Our studies herein demonstrate that sodium palmitate (C16:0) or laurate (C12:0) without BSA solubilization induced phosphorylation of inhibitor of nuclear factor-κB α, c-Jun N-terminal kinase (JNK), p44/42 mitogen-activated-kinase (ERK), and nuclear factor-κB subunit p65, and TLR target gene expression in THP1 monocytes or RAW264.7 macrophages, respectively, when cultured in low FBS (0.25%) medium. C12:0 induced NFκB activation through TLR2 dimerized with TLR1 or TLR6, and through TLR4. Because BSA was not used in these experiments, contaminants in BSA have no relevance. Unlike in suspension cells (THP-1), BSA-solubilized C16:0 instead of sodium C16:0 is required to induce TLR target gene expression in adherent cells (RAW264.7). C16:0-BSA transactivated TLR2 dimerized with TLR1 or TLR6 and through TLR4 as seen with C12:0. These results and additional studies with the LPS sequester polymixin B and in MyD88(-/-) macrophages indicated that SFA-induced activation of TLR2 or TLR4 is a fatty acid-specific effect, but not due to contaminants in BSA or fatty acid preparations.

  6. Big brown bats (Eptesicus fuscus) reveal diverse strategies for sonar target tracking in clutter.

    PubMed

    Mao, Beatrice; Aytekin, Murat; Wilkinson, Gerald S; Moss, Cynthia F

    2016-09-01

    Bats actively adjust the acoustic features of their sonar calls to control echo information specific to a given task and environment. A previous study investigated how bats adapted their echolocation behavior when tracking a moving target in the presence of a stationary distracter at different distances and angular offsets. The use of only one distracter, however, left open the possibility that a bat could reduce the interference of the distracter by turning its head. Here, bats tracked a moving target in the presence of one or two symmetrically placed distracters to investigate adaptive echolocation behavior in a situation where vocalizing off-axis would result in increased interference from distracter echoes. Both bats reduced bandwidth and duration but increased sweep rate in more challenging distracter conditions, and surprisingly, made more head turns in the two-distracter condition compared to one, but only when distracters were placed at large angular offsets. However, for most variables examined, subjects showed distinct strategies to reduce clutter interference, either by (1) changing spectral or temporal features of their calls, or (2) producing large numbers of sonar sound groups and consistent head-turning behavior. The results suggest that individual bats can use different strategies for target tracking in cluttered environments.

  7. Acoustic and foraging behavior of a Baird's beaked whale, Berardius bairdii, exposed to simulated sonar.

    PubMed

    Stimpert, A K; DeRuiter, S L; Southall, B L; Moretti, D J; Falcone, E A; Goldbogen, J A; Friedlaender, A; Schorr, G S; Calambokidis, J

    2014-11-13

    Beaked whales are hypothesized to be particularly sensitive to anthropogenic noise, based on previous strandings and limited experimental and observational data. However, few species have been studied in detail. We describe the underwater behavior of a Baird's beaked whale (Berardius bairdii) from the first deployment of a multi-sensor acoustic tag on this species. The animal exhibited shallow (23 ± 15 m max depth), intermediate (324 ± 49 m), and deep (1138 ± 243 m) dives. Echolocation clicks were produced with a mean inter-click interval of approximately 300 ms and peak frequency of 25 kHz. Two deep dives included presumed foraging behavior, with echolocation pulsed sounds (presumed prey capture attempts) associated with increased maneuvering, and sustained inverted swimming during the bottom phase of the dive. A controlled exposure to simulated mid-frequency active sonar (3.5-4 kHz) was conducted 4 hours after tag deployment, and within 3 minutes of exposure onset, the tagged whale increased swim speed and body movement, and continued to show unusual dive behavior for each of its next three dives, one of each type. These are the first data on the acoustic foraging behavior in this largest beaked whale species, and the first experimental demonstration of a response to simulated sonar.

  8. Acoustic and foraging behavior of a Baird's beaked whale, Berardius bairdii, exposed to simulated sonar

    PubMed Central

    Stimpert, A. K.; DeRuiter, S. L.; Southall, B. L.; Moretti, D. J.; Falcone, E. A.; Goldbogen, J. A.; Friedlaender, A.; Schorr, G. S.; Calambokidis, J.

    2014-01-01

    Beaked whales are hypothesized to be particularly sensitive to anthropogenic noise, based on previous strandings and limited experimental and observational data. However, few species have been studied in detail. We describe the underwater behavior of a Baird's beaked whale (Berardius bairdii) from the first deployment of a multi-sensor acoustic tag on this species. The animal exhibited shallow (23 ± 15 m max depth), intermediate (324 ± 49 m), and deep (1138 ± 243 m) dives. Echolocation clicks were produced with a mean inter-click interval of approximately 300 ms and peak frequency of 25 kHz. Two deep dives included presumed foraging behavior, with echolocation pulsed sounds (presumed prey capture attempts) associated with increased maneuvering, and sustained inverted swimming during the bottom phase of the dive. A controlled exposure to simulated mid-frequency active sonar (3.5–4 kHz) was conducted 4 hours after tag deployment, and within 3 minutes of exposure onset, the tagged whale increased swim speed and body movement, and continued to show unusual dive behavior for each of its next three dives, one of each type. These are the first data on the acoustic foraging behavior in this largest beaked whale species, and the first experimental demonstration of a response to simulated sonar. PMID:25391309

  9. Notchless encodes a novel WD40-repeat-containing protein that modulates Notch signaling activity.

    PubMed Central

    Royet, J; Bouwmeester, T; Cohen, S M

    1998-01-01

    Signaling by Notch family receptors is involved in many cell-fate decisions during development. Several modifiers of Notch activity have been identified, suggesting that regulation of Notch signaling is complex. In a genetic screen for modifiers of Notch activity, we identified a gene encoding a novel WD40-repeat protein. The gene is called Notchless, because loss-of-function mutant alleles dominantly suppress the wing notching caused by certain Notch alleles. Reducing Notchless activity increases Notch activity. Overexpression of Notchless in Xenopus or Drosophila appears to have a dominant-negative effect in that it also increases Notch activity. Biochemical studies show that Notchless binds to the cytoplasmic domain of Notch, suggesting that it serves as a direct regulator of Notch signaling activity. PMID:9857191

  10. 50 CFR 218.120 - Specified activity and geographical area.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... paragraph (b) of this section and that occur incidental to the activities described in paragraph (c) of this.... long.; 57°16′ N. lat., 151°00′ W. long.; and 55°30′ N. lat., 142°00′ W. long. (c) The taking of marine... the following mid-frequency active sonar (MFAS) sources, high-frequency active sonar (HFAS)...

  11. 50 CFR 218.120 - Specified activity and geographical area.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... paragraph (b) of this section and that occur incidental to the activities described in paragraph (c) of this.... long.; 57°16′ N. lat., 151°00′ W. long.; and 55°30′ N. lat., 142°00′ W. long. (c) The taking of marine... the following mid-frequency active sonar (MFAS) sources, high-frequency active sonar (HFAS)...

  12. Active transport improves the precision of linear long distance molecular signalling

    NASA Astrophysics Data System (ADS)

    Godec, Aljaž; Metzler, Ralf

    2016-09-01

    Molecular signalling in living cells occurs at low copy numbers and is thereby inherently limited by the noise imposed by thermal diffusion. The precision at which biochemical receptors can count signalling molecules is intimately related to the noise correlation time. In addition to passive thermal diffusion, messenger RNA and vesicle-engulfed signalling molecules can transiently bind to molecular motors and are actively transported across biological cells. Active transport is most beneficial when trafficking occurs over large distances, for instance up to the order of 1 metre in neurons. Here we explain how intermittent active transport allows for faster equilibration upon a change in concentration triggered by biochemical stimuli. Moreover, we show how intermittent active excursions induce qualitative changes in the noise in effectively one-dimensional systems such as dendrites. Thereby they allow for significantly improved signalling precision in the sense of a smaller relative deviation in the concentration read-out by the receptor. On the basis of linear response theory we derive the exact mean field precision limit for counting actively transported molecules. We explain how intermittent active excursions disrupt the recurrence in the molecular motion, thereby facilitating improved signalling accuracy. Our results provide a deeper understanding of how recurrence affects molecular signalling precision in biological cells and novel medical-diagnostic devices.

  13. Activation of the yeast Hippo pathway by phosphorylation-dependent assembly of signaling complexes.

    PubMed

    Rock, Jeremy M; Lim, Daniel; Stach, Lasse; Ogrodowicz, Roksana W; Keck, Jamie M; Jones, Michele H; Wong, Catherine C L; Yates, John R; Winey, Mark; Smerdon, Stephen J; Yaffe, Michael B; Amon, Angelika

    2013-05-17

    Scaffold-assisted signaling cascades guide cellular decision-making. In budding yeast, one such signal transduction pathway called the mitotic exit network (MEN) governs the transition from mitosis to the G1 phase of the cell cycle. The MEN is conserved and in metazoans is known as the Hippo tumor-suppressor pathway. We found that signaling through the MEN kinase cascade was mediated by an unusual two-step process. The MEN kinase Cdc15 first phosphorylated the scaffold Nud1. This created a phospho-docking site on Nud1, to which the effector kinase complex Dbf2-Mob1 bound through a phosphoserine-threonine binding domain, in order to be activated by Cdc15. This mechanism of pathway activation has implications for signal transmission through other kinase cascades and might represent a general principle in scaffold-assisted signaling.

  14. [Leukocyte mobility in modulation of activity of the cell signalling system].

    PubMed

    Luĭk, A I; Mogilevich, S E; Radchenko, I V; Kondrashova, L N

    1993-01-01

    The mobility of the rat polymorphonuclear leukocytes (PMNL) has been studied. It was shown, that it is greatly determined by the balance of adenylate cyclase (AdC) and Ca-polyphosphoinositide (Ca-PPI) cell signalling systems. Various compounds whose action on the activity of the signalling systems was previously connected with the membrane receptors, proved to be capable to affect the activity of submembrane elements of these systems. It is concluded that multiple areas of bioregulators fixation within the limits of the signal cascades are available.

  15. Microglial immunoreceptor tyrosine-based activation and inhibition motif signaling in neuroinflammation.

    PubMed

    Linnartz, Bettina; Wang, Yiner; Neumann, Harald

    2010-06-22

    Elimination of extracellular aggregates and apoptotic neural membranes without inflammation is crucial for brain tissue homeostasis. In the mammalian central nervous system, essential molecules in this process are the Fc receptors and the DAP12-associated receptors which both trigger the microglial immunoreceptor tyrosine-based activation motif- (ITAM-) Syk-signaling cascade. Microglial triggering receptor expressed on myeloid cells-2 (TREM2), signal regulatory protein-beta1, and complement receptor-3 (CD11b/CD18) signal via the adaptor protein DAP12 and activate phagocytic activity of microglia. Microglial ITAM-signaling receptors are counter-regulated by immunoreceptor tyrosine-based inhibition motif- (ITIM-) signaling molecules such as sialic acid-binding immunoglobulin superfamily lectins (Siglecs). Siglecs can suppress the proinflammatory and phagocytic activity of microglia via ITIM signaling. Moreover, microglial neurotoxicity is alleviated via interaction of Siglec-11 with sialic acids on the neuronal glycocalyx. Thus, ITAM- and ITIM-signaling receptors modulate microglial phagocytosis and cytokine expression during neuroinflammatory processes. Their dysfunction could lead to impaired phagocytic clearance and neurodegeneration triggered by chronic inflammation.

  16. Mobile phone electromagnetic radiation activates MAPK signaling and regulates viability in Drosophila.

    PubMed

    Lee, Kyu-Sun; Choi, Jong-Soon; Hong, Sae-Yong; Son, Tae-Ho; Yu, Kweon

    2008-07-01

    Mobile phones are widely used in the modern world. However, biological effects of electromagnetic radiation produced by mobile phones are largely unknown. In this report, we show biological effects of the mobile phone 835 MHz electromagnetic field (EMF) in the Drosophila model system. When flies were exposed to the specific absorption rate (SAR) 1.6 W/kg, which is the proposed exposure limit by the American National Standards Institute (ANSI), more than 90% of the flies were viable even after the 30 h exposure. However, in the SAR 4.0 W/kg strong EMF exposure, viability dropped from the 12 h exposure. These EMF exposures triggered stress response and increased the production of reactive oxygen species. The EMF exposures also activated extracellular signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling, but not p38 kinase signaling. Interestingly, SAR 1.6 W/kg activated mainly ERK signaling and expression of an anti-apoptotic gene, whereas SAR 4.0 W/kg strongly activated JNK signaling and expression of apoptotic genes. In addition, SAR 4.0 W/kg amplified the number of apoptotic cells in the fly brain. These findings demonstrate that the exposure limit on electromagnetic radiation proposed by ANSI triggered ERK-survival signaling but the strong electromagnetic radiation activated JNK-apoptotic signaling in Drosophila.

  17. Synthetic Aperture Sonar Low Frequency vs. High Frequency Automatic Contact Generation

    DTIC Science & Technology

    2010-06-01

    resurveyed the harbor with both sidescan sonar (on REMUS) and SAS (on the SSAM AUV) provided by NAVSEA Costal Systems Command. NOMWC, NAVOCEANO and...Synthetic Aperture Sonar Low Frequency vs. High Frequency Automatic Contact Generation J. R. Dubberley and M. L. Gendron Naval Research...Laboratory Code 7440.1 Building 1005 Stennis Space Center, MS 39529 USA Abstract- Synthetic Aperture Sonar (SAS) bottom mapping sensors are on the

  18. Frequency Domain Beamformer for a 3-D Sediment Volume Imaging Synthetic Aperture Sonar

    DTIC Science & Technology

    2010-06-01

    Frequency Domain Beamformer for a 3-D Sediment Volume Imaging Synthetic Aperture Sonar Jonathan R. Pearson Magoon,a Matthew A. Nelson,a Daniel D...synthetic aperture sonars (SAS). The beamformer, designed for systems with receiver arrays oriented transverse to the vehicle, performs standard delay and...volume imaging synthetic aperture sonars (SAS). The beamformer is designed for systems with receiver arrays oriented transverse to the vehicle such

  19. Technology Infusion of CodeSonar into the Space Network Ground Segment

    NASA Technical Reports Server (NTRS)

    Benson, Markland J.

    2009-01-01

    This slide presentation reviews the applicability of CodeSonar to the Space Network software. CodeSonar is a commercial off the shelf system that analyzes programs written in C, C++ or Ada for defects in the code. Software engineers use CodeSonar results as an input to the existing source code inspection process. The study is focused on large scale software developed using formal processes. The systems studied are mission critical in nature but some use commodity computer systems.

  20. Bedform Parameterization and Object Detection from Sonar Data- Application of Finger Print Algorithms

    DTIC Science & Technology

    2012-09-30

    areas with dynamic ripple bedforms and manmade structures. Our approach is to gather (1) the optical and acoustic backscatter properties of surface...sediment layers from an autonomous underwater platform and from surface vessel multibeam echosounder sonar, (2) the small scale (sub-meter) bathymetry...outputs from the finger print code (Figure 1) for use in a variety of sonar image formats (i.e. side-scan mosaic, rotary sonar images, multibeam

  1. Active control of shocks and sonic boom ground signal

    NASA Astrophysics Data System (ADS)

    Yagiz, Bedri

    The manipulation of a flow field to obtain a desired change is a much heightened subject. Active flow control has been the subject of the major research areas in fluid mechanics for the past two decades. It offers new solutions for mitigation of shock strength, sonic boom alleviation, drag minimization, reducing blade-vortex interaction noise in helicopters, stall control and the performance maximization of existing designs to meet the increasing requirements of the aircraft industries. Despite the wide variety of the potential applications of active flow control, the majority of studies have been performed at subsonic speeds. The active flow control cases were investigated in transonic speed in this study. Although the active flow control provides significant improvements, the sensibility of aerodynamic performance to design parameters makes it a nontrivial and expensive problem, so the designer has to optimize a number of different parameters. For the purpose of gaining understanding of the active flow control concepts, an automated optimization cycle process was generated. Also, the optimization cycle reduces cost and turnaround time. The mass flow coefficient, location, width and angle were chosen as design parameters to maximize the aerodynamic performance of an aircraft. As the main contribution of this study, a detailed parametric study and optimization process were presented. The second step is to appraise the practicability of weakening the shock wave and thereby reducing the wave drag in transonic flight regime using flow control devices such as two dimensional contour bump, individual jet actuator, and also the hybrid control which includes both control devices together, thereby gaining the desired improvements in aerodynamic performance of the air-vehicle. After this study, to improve the aerodynamic performance, the flow control and shape parameters are optimized separately, combined, and in a serial combination. The remarkable part of all these

  2. Crosstalk and Signaling Switches in Mitogen-Activated Protein Kinase Cascades

    PubMed Central

    Fey, Dirk; Croucher, David R.; Kolch, Walter; Kholodenko, Boris N.

    2012-01-01

    Mitogen-activated protein kinase (MAPK) cascades control cell fate decisions, such as proliferation, differentiation, and apoptosis by integrating and processing intra- and extracellular cues. However, similar MAPK kinetic profiles can be associated with opposing cellular decisions depending on cell type, signal strength, and dynamics. This implies that signaling by each individual MAPK cascade has to be considered in the context of the entire MAPK network. Here, we develop a dynamic model of feedback and crosstalk for the three major MAPK cascades; extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38), c-Jun N-terminal kinase (JNK), and also include input from protein kinase B (AKT) signaling. Focusing on the bistable activation characteristics of the JNK pathway, this model explains how pathway crosstalk harmonizes different MAPK responses resulting in pivotal cell fate decisions. We show that JNK can switch from a transient to sustained activity due to multiple positive feedback loops. Once activated, positive feedback locks JNK in a highly active state and promotes cell death. The switch is modulated by the ERK, p38, and AKT pathways. ERK activation enhances the dual specificity phosphatase (DUSP) mediated dephosphorylation of JNK and shifts the threshold of the apoptotic switch to higher inputs. Activation of p38 restores the threshold by inhibiting ERK activity via the PP1 or PP2A phosphatases. Finally, AKT activation inhibits the JNK positive feedback, thus abrogating the apoptotic switch and allowing only proliferative signaling. Our model facilitates understanding of how cancerous deregulations disturb MAPK signal processing and provides explanations for certain drug resistances. We highlight a critical role of DUSP1 and DUSP2 expression patterns in facilitating the switching of JNK activity and show how oncogene induced ERK hyperactivity prevents the normal apoptotic switch explaining the failure of certain drugs to

  3. K+ efflux agonists induce NLRP3 inflammasome activation independently of Ca2+ signaling1

    PubMed Central

    Katsnelson, Michael A.; Rucker, L. Graham; Russo, Hana M.; Dubyak, George R.

    2015-01-01

    Perturbation of intracellular ion homeostasis is a major cellular stress signal for activation of NLRP3 inflammasome signaling that results in caspase-1 mediated production of IL-1β and pyroptosis. However, the relative contributions of decreased cytosolic [K+] versus increased cytosolic [Ca2+] remain disputed and incompletely defined. We investigated roles for elevated cytosolic [Ca2+] in NLRP3 activation and downstream inflammasome signaling responses in primary murine dendritic cells and macrophages in response to two canonical NLRP3 agonists (ATP and nigericin) that facilitate primary K+ efflux by mechanistically distinct pathways or the lysosome-destabilizing agonist Leu-Leu-O-methyl ester (LLME). The study provides three major findings relevant to this unresolved area of NLRP3 regulation. First, increased cytosolic [Ca2+] was neither a necessary nor sufficient signal for the NLRP3 inflammasome cascade during activation by endogenous ATP-gated P2X7 receptor channels, the exogenous bacterial ionophore nigericin, or the lysosomotropic agent LLME. Second, agonists for three Ca2+-mobilizing G protein-coupled receptors (formyl peptide receptor/FPR; P2Y2 purinergic receptor/P2Y2R; calcium-sensing receptor/CaSR) expressed in murine dendritic cells were ineffective as activators of rapidly induced NLRP3 signaling when directly compared to the K+ efflux agonists. Third, the intracellular Ca2+ buffer, BAPTA, and the channel blocker, 2-aminoethoxydiphenyl borate (2-APB), widely used reagents for disruption of Ca2+-dependent signaling pathways, strongly suppressed nigericin-induced NLRP3 inflammasome signaling via mechanisms dissociated from their canonical or expected effects on Ca2+ homeostasis. The results indicate that the ability of K+ efflux agonists to activate NLRP3 inflammasome signaling can be dissociated from changes in cytosolic [Ca2+] as a necessary or sufficient signal. PMID:25762778

  4. Activation of proinflammatory signaling by 4-hydroxynonenal-Src adducts in aged kidneys

    PubMed Central

    Lee, Bonggi; Lee, Eun Kyeong; Chung, Ki Wung; Moon, Kyoung Mi; Kim, Min Jo; An, Hye Jin; Jeong, Ji Won; Kim, Ye Ra; Yu, Byung Pal; Chung, Hae Young

    2016-01-01

    In our previous study, reactive 4-hydroxy-2-nonenal (4-HNE) was shown to activate Src (a non-receptor tyrosine kinase) by forming an adduct on binding with a specific residue of Src, leading to the activation of proinflammatory signaling pathways in cultured cells. However, to date, the deleterious roles of 4-HNE in inflammatory signaling activation in kidneys during aging have not been explored. The purpose of the present study was to document the mechanisms by which 4-HNE induces inflammation in the kidney during aging. Initial experiments revealed that activated nuclear factor-κB (NF-κB) expression was caused by 4-HNE activation, which suppressed transcriptional activity in the aged kidney. Treatment of human umbilical vein endothelial cells with 4-HNE revealed that Src caused senescence via NF-κB activation. Furthermore, our immunohistochemistry data showed that 4-HNE-adducted Src significantly increased in aged kidney tissues. The data showed age-related upregulation of downstream signaling molecules such as mitogen activated protein kinases (MAPKs), activator protein-1 (AP-1), NF-κB, and COX-2 in a cell culture cell system. Taken together, the results of this study show that the formation of adducts between 4-HNE and Src activates inflammatory signaling pathways in the aged kidney, contributing to age-related nephropathy. PMID:27472463

  5. Characterization of swallowing sounds with the use of sonar Doppler in full-term and preterm newborns.

    PubMed

    Lagos, Hellen Nataly Correia; Santos, Rosane Sampaio; Abdulmassih, Edna Marcia da Silva; Gallinea, Liliane Friedrich; Langone, Mariangela

    2013-10-01

    Introduction Technological advances have provided a large variety of instruments to view the swallowing event, aiding in the evaluation, diagnosis, and monitoring of disturbances. These advances include electromyography of the surface, dynamic video fluoroscopy, and most recently sonar Doppler. Objective To characterize swallowing sounds in typical children through the use of sonar Doppler. Method Thirty newborns participated in this prospective study. All newborns received breast milk through either their mother's breasts or bottles during data collection. The newborns were placed in either right lateral or left lateral positions when given breast milk through their mother's breasts and in a sitting position when given a bottle. There were five variables measured: initial frequency of sound wave (FoI), frequency of the first peak of the sound wave (FoP1), frequency of the second peak of the sound wave (FoP2), initial intensity and final sound wave (II and IF), and swallowing length (T), the time elapsed from the beginning until the end of the analyzed acoustic signal measured by the audio signal, in seconds. Results The values obtained in the initial frequency of the babies had a mean of 850 Hz. In terms of frequency of first peak, only three presented with a subtle peak, which was due to the elevated larynx position. Conclusion The use of sonar Doppler as a complementary exam for clinical evaluations is of upmost importance because it is nonintrusive and painless, and it is not necessary to place patients in a special room or expose them to radiation.

  6. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression.

    PubMed

    Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A; Cardozo, Christopher P

    2011-10-14

    Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  7. Assessment of Marine Mammal Impact Zones for Use of Military Sonar in the Baltic Sea.

    PubMed

    Andersson, Mathias H; Johansson, Torbjörn

    2016-01-01

    Military sonars are known to have caused cetaceans to strand. Navies in shallow seas use different frequencies and sonar pulses, commonly frequencies between 25 and 100 kHz, compared with most studied NATO sonar systems that have been evaluated for their environmental impact. These frequencies match the frequencies of best hearing in the harbor porpoises and seals resident in the Baltic Sea. This study uses published temporary and permanent threshold shifts, measured behavioral response thresholds, technical specifications of a sonar system, and environmental parameters affecting sound propagation common for the Baltic Sea to estimate the impact zones for harbor porpoises and seals.

  8. Activation of Symbiosis Signaling by Arbuscular Mycorrhizal Fungi in Legumes and Rice[OPEN

    PubMed Central

    Sun, Jongho; Miller, J. Benjamin; Granqvist, Emma; Wiley-Kalil, Audrey; Gobbato, Enrico; Maillet, Fabienne; Cottaz, Sylvain; Samain, Eric; Venkateshwaran, Muthusubramanian; Fort, Sébastien; Morris, Richard J.; Ané, Jean-Michel; Dénarié, Jean; Oldroyd, Giles E.D.

    2015-01-01

    Establishment of arbuscular mycorrhizal interactions involves plant recognition of diffusible signals from the fungus, including lipochitooligosaccharides (LCOs) and chitooligosaccharides (COs). Nitrogen-fixing rhizobial bacteria that associate with leguminous plants also signal to their hosts via LCOs, the so-called Nod factors. Here, we have assessed the induction of symbiotic signaling by the arbuscular mycorrhizal (Myc) fungal-produced LCOs and COs in legumes and rice (Oryza sativa). We show that Myc-LCOs and tetra-acetyl chitotetraose (CO4) activate the common symbiosis signaling pathway, with resultant calcium oscillations in root epidermal cells of Medicago truncatula and Lotus japonicus. The nature of the calcium oscillations is similar for LCOs produced by rhizobial bacteria and by mycorrhizal fungi; however, Myc-LCOs activate distinct gene expression. Calcium oscillations were activated in rice atrichoblasts by CO4, but not the Myc-LCOs, whereas a mix of CO4 and Myc-LCOs activated calcium oscillations in rice trichoblasts. In contrast, stimulation of lateral root emergence occurred following treatment with Myc-LCOs, but not CO4, in M. truncatula, whereas both Myc-LCOs and CO4 were active in rice. Our work indicates that legumes and non-legumes differ in their perception of Myc-LCO and CO signals, suggesting that different plant species respond to different components in the mix of signals produced by arbuscular mycorrhizal fungi. PMID:25724637

  9. Lgd regulates the activity of the BMP/Dpp signalling pathway during Drosophila oogenesis.

    PubMed

    Morawa, Kim Sara; Schneider, Markus; Klein, Thomas

    2015-04-01

    The tumour suppressor gene lethal (2) giant discs (lgd) is involved in endosomal trafficking of transmembrane proteins in Drosophila. Loss of function results in the ligand-independent activation of the Notch pathway in all imaginal disc cells and follicle cells. Analysis of lgd loss of function has largely been restricted to imaginal discs and suggests that no other signalling pathway is affected. The devotion of Lgd to the Notch pathway was puzzling given that lgd loss of function also affects trafficking of components of other signalling pathways, such as the Dpp (a Drosophila BMP) pathway. Moreover, Lgd physically interacts with Shrub, a fundamental component of the ESCRT trafficking machinery, whose loss of function results in the activation of several signalling pathways. Here, we show that during oogenesis lgd loss of function causes ectopic activation of the Drosophila BMP signalling pathway. This activation occurs in somatic follicle cells as well as in germline cells. The activation in germline cells causes an extra round of division, producing egg chambers with 32 instead of 16 cells. Moreover, more germline stem cells were formed. The lgd mutant cells are defective in endosomal trafficking, causing an accumulation of the type I Dpp receptor Thickveins in maturing endosomes, which probably causes activation of the pathway. Taken together, these results show that lgd loss of function causes various effects among tissues and can lead to the activation of signalling pathways other than Notch. They further show that there is a role for the endosomal pathway during oogenesis.

  10. Constitutively active Lck kinase in T cells drives antigen receptor signal transduction.

    PubMed

    Nika, Konstantina; Soldani, Cristiana; Salek, Mogjiborahman; Paster, Wolfgang; Gray, Adrian; Etzensperger, Ruth; Fugger, Lars; Polzella, Paolo; Cerundolo, Vincenzo; Dushek, Omer; Höfer, Thomas; Viola, Antonella; Acuto, Oreste

    2010-06-25

    T cell antigen receptor (TCR) and coreceptor ligation is thought to initiate signal transduction by inducing activation of the kinase Lck. Here we showed that catalytically active Lck was present in unstimulated naive T cells and thymocytes and was readily detectable in these cells in lymphoid organs. In naive T cells up to approximately 40% of total Lck was constitutively activated, part of which was also phosphorylated on the C-terminal inhibitory site. Formation of activated Lck was independent of TCR and coreceptors but required Lck catalytic activity and its maintenance relied on monitoring by the HSP90-CDC37 chaperone complex to avoid degradation. The amount of activated Lck did not change after TCR and coreceptor engagement; however it determined the extent of TCR-zeta phosphorylation. Our findings suggest a dynamic regulation of Lck activity that can be promptly utilized to initiate T cell activation and have implications for signaling by other immune receptors.

  11. Algorithms for the Fusion of Two Sets of (Sonar) Data

    DTIC Science & Technology

    2006-12-01

    dB ifDT= 10. ONGERUBRICEERD ONGERUBRICEERD I TNO reportI TNO-DV 2006 A518 33/51 S........ .... -@"Z sonar 2 -> sonar 1so rI- 0.9 ... theory 0.8. 0.7...pings. ONGERUBRICEERD ONGERUBRICEERD I TNO reportI TNO-DV 2006 A518 37/51 •+• -0- Fade. - false SFire.- true 0.16 -=- True-fiji.-0= Tiuesi- trus -0...assumed SNRs. ONGERUBRICEERD ONGERUBRICEERD I TNO reportI TNO-DV 2006 A518 47/51 1 t m 1 0.0 -.-.- 4 1 o,::---::: ::.: :---’ • -’"o0

  12. Identification of Domains for Efficient Notch Signaling Activity in Immobilized Notch Ligand Proteins.

    PubMed

    Liu, Ledi; Wada, Hiroe; Matsubara, Natsuki; Hozumi, Katsuto; Itoh, Motoyuki

    2017-04-01

    Notch is a critical signaling pathway that controls cell fate and tissue homeostasis, but the functional characterization of Notch ligand domains that activate Notch receptors remains incomplete. Here, we established a method for immobilizing Notch ligand proteins onto beads to measure time-dependent Notch activity after the addition of Notch ligand-coated beads. A comparison between activities by the Notch ligand found on the cell surface to that of the ligand immobilized on beads showed that immobilized Notch ligand protein produces comparable signal activity during the first 10 h. Follow-up truncation studies showed that the N-terminal epidermal growth factor (EGF) repeat three region of delta like canonical Notch ligand 4 (DLL4) or jagged 1 (JAG1) is the minimum region for activating Notch signaling, and the DLL4 EGF repeat three domain may have a role in activation through a mechanism other than by increasing binding affinity. In addition, we found that reconstruction of the DLL4 delta and OSM-11 (DOS) motif (N257P) resulted in an increase in both binding affinity and signaling activity, which suggests that the role of the DOS motif is conserved among Notch ligands. Furthermore, active DLL4 protein on beads promoted T cell differentiation or inhibited B cell differentiation in vitro, whereas JAG1 proteins on beads did not have any effect. Taken together, our findings provide unambiguous evidence for the role of different Notch ligands and their domains in Notch signal activation, and may be potential tools for controlling Notch signaling activation. J. Cell. Biochem. 118: 785-796, 2017. © 2016 Wiley Periodicals, Inc.

  13. Go-activation endures following the presentation of a stop-signal: evidence from startle.

    PubMed

    Drummond, Neil M; Cressman, Erin K; Carlsen, Anthony N

    2017-01-01

    It has been proposed that, in a stop-signal task (SST), independent go- and stop-processes "race" to control behavior. If the go-process wins, an overt response is produced, whereas, if the stop-process wins, the response is withheld. One prediction that follows from this proposal is that, if the activation associated with one process is enhanced, it is more likely to win the race. We looked to determine whether these initiation and inhibition processes (and thus response outcomes) could be manipulated by using a startling acoustic stimulus (SAS), which has been shown to provide additional response activation. In the present study, participants were to respond to a visual go-stimulus; however, if a subsequent stop-signal appeared, they were to inhibit the response. The stop-signal was presented at a delay corresponding to a probability of responding of 0.4 (determined from a baseline block of trials). On stop-trials, a SAS was presented either simultaneously with the go-signal or stop-signal or 100, 150, or 200 ms following the stop-signal. Results showed that presenting a SAS during stop-trials led to an increase in probability of responding when presented with or following the stop-signal. The latency of SAS responses at the stop-signal + 150 ms and stop-signal + 200 ms probe times suggests that they would have been voluntarily inhibited but instead were involuntarily initiated by the SAS. Thus results demonstrate that go-activation endures even 200 ms following a stop-signal and remains accessible well after the response has been inhibited, providing evidence against a winner-take-all race between independent go- and stop-processes.

  14. Function Analysis of AN/SQS-510 Hull Mounted Sonar

    DTIC Science & Technology

    2001-12-01

    Which Support Behavioural Function The hardware dependency of a function will be considered in general this is the AN SQS 510 system Superordinate...Identifying mission types • Using the preliminary function list to identify all major system functions • Organising the functions into a relationship...Humansystems Incorporated® AN SQSSlO Sonar: Function Analysis Page9 P517348.PDF [Page: 20 of 91] 4. Results The results are organised as follows

  15. Wideband Sonar Arrays for UUV and Weapon System Applications

    DTIC Science & Technology

    2012-11-01

    transducers find many applications in underwater vehicles. Two methods can be used to design wideband acoustic transducers . The multiply resonant transducer ...differences, and none has investigated the possible additional benefits of combining the two methods in a single transducer element for greater benefit than is...Medeiros CO-PI Information: None Abstract Wideband sonar transducers find many applications in underwater vehicles. Two methods can be used to

  16. Suppression of hedgehog signaling regulates hepatic stellate cell activation and collagen secretion.

    PubMed

    Li, Tao; Leng, Xi-Sheng; Zhu, Ji-Ye; Wang, Gang

    2015-01-01

    Hepatic stellate cells (HSCs) play an important role in liver fibrosis. This study investigates the expression of hedgehog in HSC and the role of hedgehog signaling on activation and collagen secretion of HSC. Liver ex vivo perfusion with collagenase IV and density gradient centrifugation were used to isolate HSC. Expression of hedgehog signaling components Ihh, Smo, Ptc, Gli2 and Gli3 in HSC were detected by RT-PCR. Hedgehog siRNA vectors targeting Ihh, Smo and Gli2 were constructed and transfected into HSC respectively. Suppression of hedgehog signaling were detected by SYBR Green fluorescence quantitative RT-PCR. Effects of hedgehog signaling inhibition on HSC activation and collagen I secretion were analyzed. Hedgehog signaling components Ihh, Smo, Ptc, Gli2 and Gli3 were expressed in HSC. siRNA vectors targeting Ihh, Smo and Gli2 were successfully constructed and decreased target gene expression. Suppression of hedgehog signaling significantly decreased the expression of α-SMA in HSC (P<0.01). Collagen type I secretion of HSC were also significantly decreased (P<0.01). In summary, HSC activation and collagen secretion can be regulated by hedgehog signaling. Hedgehog may play a role in the pathogenesis of liver fibrosis.

  17. Hyperactivated Wnt signaling induces synthetic lethal interaction with Rb inactivation by elevating TORC1 activities.

    PubMed

    Zhang, Tianyi; Liao, Yang; Hsu, Fu-Ning; Zhang, Robin; Searle, Jennifer S; Pei, Xun; Li, Xuan; Ryoo, Hyung Don; Ji, Jun-Yuan; Du, Wei

    2014-05-01

    Inactivation of the Rb tumor suppressor can lead to increased cell proliferation or cell death depending on specific cellular context. Therefore, identification of the interacting pathways that modulate the effect of Rb loss will provide novel insights into the roles of Rb in cancer development and promote new therapeutic strategies. Here, we identify a novel synthetic lethal interaction between Rb inactivation and deregulated Wg/Wnt signaling through unbiased genetic screens. We show that a weak allele of axin, which deregulates Wg signaling and increases cell proliferation without obvious effects on cell fate specification, significantly alters metabolic gene expression, causes hypersensitivity to metabolic stress induced by fasting, and induces synergistic apoptosis with mutation of fly Rb ortholog, rbf. Furthermore, hyperactivation of Wg signaling by other components of the Wg pathway also induces synergistic apoptosis with rbf. We show that hyperactivated Wg signaling significantly increases TORC1 activity and induces excessive energy stress with rbf mutation. Inhibition of TORC1 activity significantly suppressed synergistic cell death induced by hyperactivated Wg signaling and rbf inactivation, which is correlated with decreased energy stress and decreased induction of apoptotic regulator expression. Finally the synthetic lethality between Rb and deregulated Wnt signaling is conserved in mammalian cells and that inactivation of Rb and APC induces synergistic cell death through a similar mechanism. These results suggest that elevated TORC1 activity and metabolic stress underpin the evolutionarily conserved synthetic lethal interaction between hyperactivated Wnt signaling and inactivated Rb tumor suppressor.

  18. MECHANISTIC PATHWAYS AND BIOLOGICAL ROLES FOR RECEPTOR-INDEPENDENT ACTIVATORS OF G-PROTEIN SIGNALING

    PubMed Central

    Blumer, Joe B.; Smrcka, Alan V.; Lanier, S.M.

    2007-01-01

    Signal processing via heterotrimeric G-proteins in response to cell surface receptors is a central and much investigated aspect of how cells integrate cellular stimuli to produce coordinated biological responses. The system is a target of numerous therapeutic agents, plays an important role in adaptive processes of organs, and aberrant processing of signals through these transducing systems is a component of various disease states. In addition to GPCR-mediated activation of G-protein signaling, nature has evolved creative ways to manipulate and utilize the Gαβγ heterotrimer or Gα and Gαβγ subunits independent of the cell surface receptor stimuli. In such situations, the G-protein subunits (Gα and Gαβγ) may actually be complexed with alternative binding partners independent of the typical heterotrimeric Gαβγ. Such regulatory accessory proteins include the family of RGS proteins that accelerate the GTPase activity of Gα and various entities that influence nucleotide binding properties and/or subunit interaction. The latter group of proteins includes receptor independent activators of G-protein signaling or AGS proteins that play surprising roles in signal processing. This review provides an overview of our current knowledge regarding AGS proteins. AGS proteins are indicative of a growing number of accessory proteins that influence signal propagation, facilitate cross talk between various types of signaling pathways and provide a platform for diverse functions of both the heterotrimeric Gαβγ and the individual Gα and Gαβγ subunits. PMID:17240454

  19. An active nuclear retention signal in the glucocorticoid receptor functions as a strong inducer of transcriptional activation.

    PubMed

    Carrigan, Amanda; Walther, Rhian F; Salem, Houssein Abdou; Wu, Dongmei; Atlas, Ella; Lefebvre, Yvonne A; Haché, Robert J G

    2007-04-13

    The glucocorticoid receptor (GR) cycles between a naive chaperone-complexed form in the cytoplasm and a transcriptionally active steroid-bound nuclear form. Nuclear import of GR occurs rapidly and is mediated through the importin alpha/beta karyopherin import pathway. By contrast, nuclear export of GR occurs only slowly under most conditions, despite a dependence on active signaling. In this study we have defined a nuclear retention signal (NRS) in the hinge region of GR that actively opposes the nuclear export of GR as well as the nuclear export mediated through an ectopic CRM1-dependent nuclear export signal (NES). The GR NRS overlaps closely with the basic NL1 nuclear localization signal (NLS) but can be distinguished from NL1 by targeted mutagenesis. Substitution of the classical NLS from SV40 T antigen for the GR NL1 results in a receptor in which nuclear export is accelerated. Remarkably, although the SV40-modified GR remains predominantly nuclear in the presence of steroid and is recruited to transcriptional regulatory regions indistinguishably from wild-type GR, the substitution dramatically weakens the ability of GR to activate transcription of a mouse mammary tumor virus reporter gene. These results suggest that active nuclear retention of GR plays an integral role in glucocorticoid signaling.

  20. Blue whales respond to simulated mid-frequency military sonar.

    PubMed

    Goldbogen, Jeremy A; Southall, Brandon L; DeRuiter, Stacy L; Calambokidis, John; Friedlaender, Ari S; Hazen, Elliott L; Falcone, Erin A; Schorr, Gregory S; Douglas, Annie; Moretti, David J; Kyburg, Chris; McKenna, Megan F; Tyack, Peter L

    2013-08-22

    Mid-frequency military (1-10 kHz) sonars have been associated with lethal mass strandings of deep-diving toothed whales, but the effects on endangered baleen whale species are virtually unknown. Here, we used controlled exposure experiments with simulated military sonar and other mid-frequency sounds to measure behavioural responses of tagged blue whales (Balaenoptera musculus) in feeding areas within the Southern California Bight. Despite using source levels orders of magnitude below some operational military systems, our results demonstrate that mid-frequency sound can significantly affect blue whale behaviour, especially during deep feeding modes. When a response occurred, behavioural changes varied widely from cessation of deep feeding to increased swimming speed and directed travel away from the sound source. The variability of these behavioural responses was largely influenced by a complex interaction of behavioural state, the type of mid-frequency sound and received sound level. Sonar-induced disruption of feeding and displacement from high-quality prey patches could have significant and previously undocumented impacts on baleen whale foraging ecology, individual fitness and population health.

  1. Blue whales respond to simulated mid-frequency military sonar

    PubMed Central

    Goldbogen, Jeremy A.; Southall, Brandon L.; DeRuiter, Stacy L.; Calambokidis, John; Friedlaender, Ari S.; Hazen, Elliott L.; Falcone, Erin A.; Schorr, Gregory S.; Douglas, Annie; Moretti, David J.; Kyburg, Chris; McKenna, Megan F.; Tyack, Peter L.

    2013-01-01

    Mid-frequency military (1–10 kHz) sonars have been associated with lethal mass strandings of deep-diving toothed whales, but the effects on endangered baleen whale species are virtually unknown. Here, we used controlled exposure experiments with simulated military sonar and other mid-frequency sounds to measure behavioural responses of tagged blue whales (Balaenoptera musculus) in feeding areas within the Southern California Bight. Despite using source levels orders of magnitude below some operational military systems, our results demonstrate that mid-frequency sound can significantly affect blue whale behaviour, especially during deep feeding modes. When a response occurred, behavioural changes varied widely from cessation of deep feeding to increased swimming speed and directed travel away from the sound source. The variability of these behavioural responses was largely influenced by a complex interaction of behavioural state, the type of mid-frequency sound and received sound level. Sonar-induced disruption of feeding and displacement from high-quality prey patches could have significant and previously undocumented impacts on baleen whale foraging ecology, individual fitness and population health. PMID:23825206

  2. Activation of GRP/GRP-R signaling contributes to castration-resistant prostate cancer progression

    PubMed Central

    Qiao, Jingbo; Grabowska, Magdalena M.; Forestier, Ingrid S.; Mirosevich, Janni; Case, Thomas C.; Chung, Dai H.; Cates, Justin M.M.; Matusik, Robert J.; Manning, H. Charles; Jin, Renjie

    2016-01-01

    Numerous studies indicate that androgen receptor splice variants (ARVs) play a critical role in the development of castration-resistant prostate cancer (CRPC), including the resistance to the new generation of inhibitors of androgen receptor (AR) action. Previously, we demonstrated that activation of NF-κB signaling increases ARVs expression in prostate cancer (PC) cells, thereby promoting progression to CRPC. However, it is unclear how NF-κB signaling is activated in CRPC. In this study, we report that long-term treatment with anti-androgens increases a neuroendocrine (NE) hormone — gastrin-releasing peptide (GRP) and its receptor (GRP-R) expression in PC cells. In addition, activation of GRP/GRP-R signaling increases ARVs expression through activating NF-κB signaling. This results in an androgen-dependent tumor progressing to a castrate resistant tumor. The knock-down of AR-V7 restores sensitivity to antiandrogens of PC cells over-expressing the GRP/GRP-R signaling pathway. These findings strongly indicate that the axis of Androgen-Deprivation Therapy (ADT) induces GRP/GRP-R activity, activation NF-κB and increased levels of AR-V7 expression resulting in progression to CRPC. Both prostate adenocarcinoma and small cell NE prostate cancer express GRP-R. Since the GRP-R is clinically targetable by analogue-based approach, this provides a novel therapeutic approach to treat advanced CRPC. PMID:27542219

  3. Carbon nanotube-assisted optical activation of TGF-β signalling by near-infrared light

    NASA Astrophysics Data System (ADS)

    Lin, Liang; Liu, Ling; Zhao, Bing; Xie, Ran; Lin, Wei; Li, He; Li, Yaya; Shi, Minlong; Chen, Ye-Guang; Springer, Timothy A.; Chen, Xing

    2015-05-01

    Receptor-mediated signal transduction modulates complex cellular behaviours such as cell growth, migration and differentiation. Although photoactivatable proteins have emerged as a powerful tool for controlling molecular interactions and signalling cascades at precise times and spaces using light, many of these light-sensitive proteins are activated by ultraviolent or visible light, which has limited tissue penetration. Here, we report a single-walled carbon nanotube (SWCNT)-assisted approach that enables near-infrared light-triggered activation of transforming growth factor β (TGF-β) signal transduction, an important signalling pathway in embryonic development and cancer progression. The protein complex of TGF-β and its latency-associated peptide is conjugated onto SWCNTs, where TGF-β is inactive. Upon near-infrared irradiation, TGF-β is released through the photothermal effect of SWCNTs and becomes active. The released TGF-β activates downstream signal transduction in live cells and modulates cellular behaviours. Furthermore, preliminary studies show that the method can be used to mediate TGF-β signalling in living mice.

  4. ACTIVATION OF THE EGF RECEPTOR SIGNALING PATHWAY IN HUMAN AIRWAY EPITHELIAL CELLS EXPOSED TO METALS

    EPA Science Inventory

    We have previously shown that exposure to combustion-derived metals rapidly (within 20 min) activated mitogen-activated protein kinases (MAPK), including extracellular signal-regulated kinase (ERK), in the human bronchial epithelial cell line BEAS. To study the mechanisms respons...

  5. Blockade of constitutively activated ERK signaling enhances cytotoxicity of microtubule-destabilizing agents in tumor cells.

    PubMed

    Tanimura, Susumu; Uchiyama, Aya; Watanabe, Kazushi; Yasunaga, Masahiro; Inada, Yoshiyuki; Kawabata, Takumi; Iwashita, Ken-Ichi; Noda, Sinji; Ozaki, Kei-Ichi; Kohno, Michiaki

    2009-01-16

    The extracellular signal-regulated kinase (ERK) signaling pathway is constitutively activated in many human tumor cell types. Given the cytoprotective role of this pathway, we examined whether its specific blockade might sensitize human tumor cells to the induction of apoptosis by various anticancer drugs. Although blockade of ERK signaling alone did not induce substantial cell death, it resulted in marked and selective enhancement of the induction of apoptosis by microtubule-destabilizing agents in tumor cells in which the ERK pathway is constitutively activated. The synergistic activation of c-Jun NH(2)-terminal kinase by the combination of an ERK pathway inhibitor and a microtubule-destabilizing agent appeared to be responsible, at least in part, for this effect. These results suggest that administration of the combination of an ERK pathway inhibitor and a microtubule-destabilizing agent is a potential chemotherapeutic strategy for the treatment of tumor cells with constitutive activation of the ERK pathway.

  6. Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function

    PubMed Central

    Muhammad, Karzan; Reddy-Alla, Suneel; Driller, Jan H; Schreiner, Dietmar; Rey, Ulises; Böhme, Mathias A.; Hollmann, Christina; Ramesh, Niraja; Depner, Harald; Lützkendorf, Janine; Matkovic, Tanja; Götz, Torsten; Bergeron, Dominique D.; Schmoranzer, Jan; Goettfert, Fabian; Holt, Mathew; Wahl, Markus C.; Hell, Stefan W.; Scheiffele, Peter; Walter, Alexander M.; Loll, Bernhard; Sigrist, Stephan J.

    2015-01-01

    Assembly and maturation of synapses at the Drosophila neuromuscular junction (NMJ) depend on trans-synaptic neurexin/neuroligin signalling, which is promoted by the scaffolding protein Syd-1 binding to neurexin. Here we report that the scaffold protein spinophilin binds to the C-terminal portion of neurexin and is needed to limit neurexin/neuroligin signalling by acting antagonistic to Syd-1. Loss of presynaptic spinophilin results in the formation of excess, but atypically small active zones. Neuroligin-1/neurexin-1/Syd-1 levels are increased at spinophilin mutant NMJs, and removal of single copies of the neurexin-1, Syd-1 or neuroligin-1 genes suppresses the spinophilin-active zone phenotype. Evoked transmission is strongly reduced at spinophilin terminals, owing to a severely reduced release probability at individual active zones. We conclude that presynaptic spinophilin fine-tunes neurexin/neuroligin signalling to control active zone number and functionality, thereby optimizing them for action potential-induced exocytosis. PMID:26471740

  7. Analysis of EMG Signals in Aggressive and Normal Activities by Using Higher-Order Spectra

    PubMed Central

    Sezgin, Necmettin

    2012-01-01

    The analysis and classification of electromyography (EMG) signals are very important in order to detect some symptoms of diseases, prosthetic arm/leg control, and so on. In this study, an EMG signal was analyzed using bispectrum, which belongs to a family of higher-order spectra. An EMG signal is the electrical potential difference of muscle cells. The EMG signals used in the present study are aggressive or normal actions. The EMG dataset was obtained from the machine learning repository. First, the aggressive and normal EMG activities were analyzed using bispectrum and the quadratic phase coupling of each EMG episode was determined. Next, the features of the analyzed EMG signals were fed into learning machines to separate the aggressive and normal actions. The best classification result was 99.75%, which is sufficient to significantly classify the aggressive and normal actions. PMID:23193379

  8. Role of Mitochondrial Reactive Oxygen Species in the Activation of Cellular Signals, Molecules, and Function.

    PubMed

    Indo, Hiroko P; Hawkins, Clare L; Nakanishi, Ikuo; Matsumoto, Ken-Ichiro; Matsui, Hirofumi; Suenaga, Shigeaki; Davies, Michael J; St Clair, Daret K; Ozawa, Toshihiko; Majima, Hideyuki J

    2017-02-08

    Mitochondria are a major source of intracellular energy and reactive oxygen species in cells, but are also increasingly being recognized as a controller of cell death. Here, we review evidence of signal transduction control by mitochondrial superoxide generation via the nuclear factor-κB (NF-κB) and GATA signaling pathways. We have also reviewed the effects of ROS on the activation of MMP and HIF. There is significant evidence to support the hypothesis that mitochondrial superoxide can initiate signaling pathways following transport into the cytosol. In this study, we provide evidence of TATA signal transductions by mitochondrial superoxide. Oxidative phosphorylation via the electron transfer chain, glycolysis, and generation of superoxide from mitochondria could be important factors in regulating signal transduction, cellular homeostasis, and cell death.

  9. Supramolecular organizing centers (SMOCs) as signaling machines in innate immune activation.

    PubMed

    Qiao, Qi; Wu, Hao

    2015-11-01

    Innate immunity offers the first line of defense against infections and other types of danger such as tumorigenesis. Its discovery provides tremendous therapeutic opportunities for numerous human diseases. Delving into the structural basis of signal transduction by innate immune receptors, our lab has recently helped to establish the new paradigm in which innate immune receptors transduce ligand-binding signals through formation of higher-order assemblies containing intracellular adapters, signaling enzymes and their substrates. These large signalosome assemblies may be visible under light microscopy as punctate structures in the µm scale, connecting to the underlying molecular structures in the nm scale. They drive proximity-induced enzyme activation, and provide a mechanism for signaling amplification by nucleated polymerization. These supramolecular signaling complexes also open new questions on their cellular organization and mode of regulation, pose challenges to our methodology, and afford valuable implications in drug discovery against these medically important pathways.

  10. Control of macrophage metabolism and activation by mTOR and Akt signaling

    PubMed Central

    Covarrubias, Anthony J.; Aksoylar, H. Ibrahim; Horng, Tiffany

    2015-01-01

    Macrophages are pleiotropic cells that assume a variety of functions depending on their tissue of residence and tissue state. They maintain homeostasis as well as coordinate responses to stresses such as infection and metabolic challenge. The ability of macrophages to acquire diverse, context-dependent activities requires their activation (or polarization) to distinct functional states. While macrophage activation is well understood at the level of signal transduction and transcriptional regulation, the metabolic underpinnings are poorly understood. Importantly, emerging studies indicate that metabolic shifts play a pivotal role in control of macrophage activation and acquisition of context-dependent effector activities. The signals that drive macrophage activation impinge on metabolic pathways, allowing for coordinate control of macrophage activation and metabolism. Here we discuss how mTOR and Akt, major metabolic regulators and targets of such activation signals, control macrophage metabolism and activation. Dysregulated macrophage activities contribute to many diseases, including infectious, inflammatory, and metabolic diseases and cancer, thus a better understanding of metabolic control of macrophage activation could pave the way to the development of new therapeutic strategies. PMID:26360589

  11. Control of macrophage metabolism and activation by mTOR and Akt signaling.

    PubMed

    Covarrubias, Anthony J; Aksoylar, H Ibrahim; Horng, Tiffany

    2015-08-01

    Macrophages are pleiotropic cells that assume a variety of functions depending on their tissue of residence and tissue state. They maintain homeostasis as well as coordinate responses to stresses such as infection and metabolic challenge. The ability of macrophages to acquire diverse, context-dependent activities requires their activation (or polarization) to distinct functional states. While macrophage activation is well understood at the level of signal transduction and transcriptional regulation, the metabolic underpinnings are poorly understood. Importantly, emerging studies indicate that metabolic shifts play a pivotal role in control of macrophage activation and acquisition of context-dependent effector activities. The signals that drive macrophage activation impinge on metabolic pathways, allowing for coordinate control of macrophage activation and metabolism. Here we discuss how mTOR and Akt, major metabolic regulators and targets of such activation signals, control macrophage metabolism and activation. Dysregulated macrophage activities contribute to many diseases, including infectious, inflammatory, and metabolic diseases and cancer, thus a better understanding of metabolic control of macrophage activation could pave the way to the development of new therapeutic strategies.

  12. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma.

    PubMed

    Davis, R Eric; Ngo, Vu N; Lenz, Georg; Tolar, Pavel; Young, Ryan M; Romesser, Paul B; Kohlhammer, Holger; Lamy, Laurence; Zhao, Hong; Yang, Yandan; Xu, Weihong; Shaffer, Arthur L; Wright, George; Xiao, Wenming; Powell, John; Jiang, Jian-Kang; Thomas, Craig J; Rosenwald, Andreas; Ott, German; Muller-Hermelink, Hans Konrad; Gascoyne, Randy D; Connors, Joseph M; Johnson, Nathalie A; Rimsza, Lisa M; Campo, Elias; Jaffe, Elaine S; Wilson, Wyndham H; Delabie, Jan; Smeland, Erlend B; Fisher, Richard I; Braziel, Rita M; Tubbs, Raymond R; Cook, J R; Weisenburger, Dennis D; Chan, Wing C; Pierce, Susan K; Staudt, Louis M

    2010-01-07

    A role for B-cell-receptor (BCR) signalling in lymphomagenesis has been inferred by studying immunoglobulin genes in human lymphomas and by engineering mouse models, but genetic and functional evidence for its oncogenic role in human lymphomas is needed. Here we describe a form of 'chronic active' BCR signalling that is required for cell survival in the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). The signalling adaptor CARD11 is required for constitutive NF-kappaB pathway activity and survival in ABC DLBCL. Roughly 10% of ABC DLBCLs have mutant CARD11 isoforms that activate NF-kappaB, but the mechanism that engages wild-type CARD11 in other ABC DLBCLs was unknown. An RNA interference genetic screen revealed that a BCR signalling component, Bruton's tyrosine kinase, is essential for the survival of ABC DLBCLs with wild-type CARD11. In addition, knockdown of proximal BCR subunits (IgM, Ig-kappa, CD79A and CD79B) killed ABC DLBCLs with wild-type CARD11 but not other lymphomas. The BCRs in these ABC DLBCLs formed prominent clusters in the plasma membrane with low diffusion, similarly to BCRs in antigen-stimulated normal B cells. Somatic mutations affecting the immunoreceptor tyrosine-based activation motif (ITAM) signalling modules of CD79B and CD79A were detected frequently in ABC DLBCL biopsy samples but rarely in other DLBCLs and never in Burkitt's lymphoma or mucosa-associated lymphoid tissue lymphoma. In 18% of ABC DLBCLs, one functionally critical residue of CD79B, the first ITAM tyrosine, was mutated. These mutations increased surface BCR expression and attenuated Lyn kinase, a feedback inhibitor of BCR signalling. These findings establish chronic active BCR signalling as a new pathogenetic mechanism in ABC DLBCL, suggesting several therapeutic strategies.

  13. Context-dependent activation of Wnt signaling by tumor suppressor RUNX3 in gastric cancer cells.

    PubMed

    Ju, Xiaoli; Ishikawa, Tomo-O; Naka, Kazuhito; Ito, Kosei; Ito, Yoshiaki; Oshima, Masanobu

    2014-04-01

    RUNX3 is a tumor suppressor for a variety of cancers. RUNX3 suppresses the canonical Wnt signaling pathway by binding to the TCF4/β-catenin complex, resulting in the inhibition of binding of the complex to the Wnt target gene promoter. Here, we confirmed that RUNX3 suppressed Wnt signaling activity in several gastric cancer cell lines; however, we found that RUNX3 increased the Wnt signaling activity in KatoIII and SNU668 gastric cancer cells. Notably, RUNX3 expression increased the ratio of the Wnt signaling-high population in the KatoIII cells. although the maximum Wnt activation level of individual cells was similar to that in the control. As found previously, RUNX3 also binds to TCF4 and β-catenin in KatoIII cells, suggesting that these molecules form a ternary complex. Moreover, the ChIP analyses revealed that TCF4, β-catenin and RUNX3 bind the promoter region of the Wnt target genes, Axin2 and c-Myc, and the occupancy of TCF4 and β-catenin in these promoter regions is increased by the RUNX3 expression. These results suggest that RUNX3 stabilizes the TCF4/β-catenin complex on the Wnt target gene promoter in KatoIII cells, leading to activation of Wnt signaling. Although RUNX3 increased the Wnt signaling activity, its expression resulted in suppression of tumorigenesis of KatoIII cells, indicating that RUNX3 plays a tumor-suppressing role in KatoIII cells through a Wnt-independent mechanism. These results indicate that RUNX3 can either suppress or activate the Wnt signaling pathway through its binding to the TCF4/β-catenin complex by cell context-dependent mechanisms.

  14. Biophysical assay for tethered signaling reactions reveals tether-controlled activity for the phosphatase SHP-1.

    PubMed

    Goyette, Jesse; Salas, Citlali Solis; Coker-Gordon, Nicola; Bridge, Marcus; Isaacson, Samuel A; Allard, Jun; Dushek, Omer

    2017-03-01

    Tethered enzymatic reactions are ubiquitous in signaling networks but are poorly understood. A previously unreported mathematical analysis is established for tethered signaling reactions in surface plasmon resonance (SPR). Applying the method to the phosphatase SHP-1 interacting with a phosphorylated tether corresponding to an immune receptor cytoplasmic tail provides five biophysical/biochemical constants from a single SPR experiment: two binding rates, two catalytic rates, and a reach parameter. Tether binding increases the activity of SHP-1 by 900-fold through a binding-induced allosteric activation (20-fold) and a more significant increase in local substrate concentration (45-fold). The reach parameter indicates that this local substrate concentration is exquisitely sensitive to receptor clustering. We further show that truncation of the tether leads not only to a lower reach but also to lower binding and catalysis. This work establishes a new framework for studying tethered signaling processes and highlights the tether as a control parameter in clustered receptor signaling.

  15. Biophysical assay for tethered signaling reactions reveals tether-controlled activity for the phosphatase SHP-1

    PubMed Central

    Goyette, Jesse; Salas, Citlali Solis; Coker-Gordon, Nicola; Bridge, Marcus; Isaacson, Samuel A.; Allard, Jun; Dushek, Omer

    2017-01-01

    Tethered enzymatic reactions are ubiquitous in signaling networks but are poorly understood. A previously unreported mathematical analysis is established for tethered signaling reactions in surface plasmon resonance (SPR). Applying the method to the phosphatase SHP-1 interacting with a phosphorylated tether corresponding to an immune receptor cytoplasmic tail provides five biophysical/biochemical constants from a single SPR experiment: two binding rates, two catalytic rates, and a reach parameter. Tether binding increases the activity of SHP-1 by 900-fold through a binding-induced allosteric activation (20-fold) and a more significant increase in local substrate concentration (45-fold). The reach parameter indicates that this local substrate concentration is exquisitely sensitive to receptor clustering. We further show that truncation of the tether leads not only to a lower reach but also to lower binding and catalysis. This work establishes a new framework for studying tethered signaling processes and highlights the tether as a control parameter in clustered receptor signaling. PMID:28378014

  16. The Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway as a Discovery Target in Stroke.

    PubMed

    Sun, Jing; Nan, Guangxian

    2016-05-01

    Protein kinases are critical modulators of a variety of intracellular and extracellular signal transduction pathways, and abnormal phosphorylation events can contribute to disease progression in a variety of diseases. As a result, protein kinases have emerged as important new drug targets for small molecule therapeutics. The mitogen-activated protein kinase (MAPK) signaling pathway transmits signals from the cell membrane to the nucleus in response to a variety of different stimuli. Because this pathway controls a broad spectrum of cellular processes, including growth, inflammation, and stress responses, it is accepted as a therapeutic target for cancer and peripheral inflammatory disorders. There is also increasing evidence that MAPK is an important regulator of ischemic and hemorrhagic cerebral vascular disease, raising the possibility that it might be a drug discovery target for stroke. In this review, we discuss the MAPK signaling pathway in association with its activation in stroke-induced brain injury.

  17. Sonar Dome Reliability XVIII: Measured Deflections of the USS Kauffman Sonar Rubber Dome, 15-25 November 1992

    DTIC Science & Technology

    1994-01-07

    there was insufficient room left in the existing cableways for the addition of our system control cables. Thus, we requested a new cableway be installed...between the SRD area and the sonar equipment room, shown in Figures 6 and 7, to provide a pathway for these new cables. The new cableway would also...decided that a new separate cableway was not needed; the installation of the wave height sensors was made parallel with the ships rail instead of the

  18. The c-Jun kinase signaling cascade promotes glial engulfment activity through activation of draper and phagocytic function.

    PubMed

    Macdonald, J M; Doherty, J; Hackett, R; Freeman, M R

    2013-09-01

    After neuronal injury or death glial cells become reactive, exhibiting dramatic changes in morphology and patterns of gene expression and ultimately engulfing neuronal debris. Rapid clearance of degenerating neuronal material is thought to be crucial for suppression of inflammation and promotion of functional recovery. Here we demonstrate that Drosophila c-Jun N-terminal kinase (dJNK) signaling is a critical in vivo mediator of glial engulfment activity. In response to axotomy, we find glial dJNK signals through a cascade involving the upstream mitogen-activated protein kinase kinase kinases Slipper and Tak1, the mitogen-activated protein kinase kinase MKK4, and ultimately the Drosophila activator protein 1 (AP-1) transcriptional complex composed of Jra and Kayak to initiate glial phagocytosis of degenerating axons. Interestingly, loss of dJNK also blocked injury-induced upregulation of Draper levels in glia, and glial-specific overexpression of Draper was sufficient to rescue engulfment defects associated with loss of dJNK signaling. This work identifies that the dJNK pathway is a novel mediator of glial engulfment activity and a primary role for the glial Slipper/Tak1 →MKK4 →dJNK →dAP-1 signaling cascade appears to be activation of draper expression after axon injury.

  19. Cooperativity between MAPK and PI3K signaling activation is required for glioblastoma pathogenesis

    PubMed Central

    Vitucci, Mark; Karpinich, Natalie O.; Bash, Ryan E.; Werneke, Andrea M.; Schmid, Ralf S.; White, Kristen K.; McNeill, Robert S.; Huff, Byron; Wang, Sophie; Van Dyke, Terry; Miller, C. Ryan

    2013-01-01

    Background Glioblastoma (GBM) genomes feature recurrent genetic alterations that dysregulate core intracellular signaling pathways, including the G1/S cell cycle checkpoint and the MAPK and PI3K effector arms of receptor tyrosine kinase (RTK) signaling. Elucidation of the phenotypic consequences of activated RTK effectors is required for the design of effective therapeutic and diagnostic strategies. Methods Genetically defined, G1/S checkpoint-defective cortical murine astrocytes with constitutively active Kras and/or Pten deletion mutations were used to systematically investigate the individual and combined roles of these 2 RTK signaling effectors in phenotypic hallmarks of glioblastoma pathogenesis, including growth, migration, and invasion in vitro. A novel syngeneic orthotopic allograft model system was used to examine in vivo tumorigenesis. Results Constitutively active Kras and/or Pten deletion mutations activated both MAPK and PI3K signaling. Their combination led to maximal growth, migration, and invasion of G1/S-defective astrocytes in vitro and produced progenitor-like transcriptomal profiles that mimic human proneural GBM. Activation of both RTK effector arms was required for in vivo tumorigenesis and produced highly invasive, proneural-like GBM. Conclusions These results suggest that cortical astrocytes can be transformed into GBM and that combined dysregulation of MAPK and PI3K signaling revert G1/S-defective astrocytes to a primitive gene expression state. This genetically-defined, immunocompetent model of proneural GBM will be useful for preclinical development of MAPK/PI3K-targeted, subtype-specific therapies. PMID:23814263

  20. Integrin-Dependent Activation of the JNK Signaling Pathway by Mechanical Stress

    PubMed Central

    Kanger, Johannes S.; Subramaniam, Vinod; Martin-Blanco, Enrique

    2011-01-01

    Mechanical force is known to modulate the activity of the Jun N-terminal kinase (JNK) signaling cascade. However, the effect of mechanical stresses on JNK signaling activation has previously only been analyzed by in vitro detection methods. It still remains unknown how living cells activate the JNK signaling cascade in response to mechanical stress and what its functions are in stretched cells. We assessed in real-time the activity of the JNK pathway in Drosophila cells by Fluorescence Lifetime Imaging Microscopy (FLIM), using an intramolecular phosphorylation-dependent dJun-FRET (Fluorescence Resonance Energy Transfer) biosensor. We found that quantitative FRET-FLIM analysis and confocal microscopy revealed sustained dJun-FRET biosensor activation and stable morphology changes in response to mechanical stretch for Drosophila S2R+ cells. Further, these cells plated on different substrates showed distinct levels of JNK activity that associate with differences in cell morphology, integrin expression and focal adhesion organization. These data imply that alterations in the cytoskeleton and matrix attachments may act as regulators of JNK signaling, and that JNK activity might feed back to modulate the cytoskeleton and cell adhesion. We found that this dynamic system is highly plastic; at rest, integrins at focal adhesions and talin are key factors suppressing JNK activity, while multidirectional static stretch leads to integrin-dependent, and probably talin-independent, Jun sensor activation. Further, our data suggest that JNK activity has to coordinate with other signaling elements for the regulation of the cytoskeleton and cell shape remodeling associated with stretch. PMID:22180774

  1. Relationship Between Pak-Mediated Cell Death and Stress-Activated Kinase Signaling in Breast Cancer

    DTIC Science & Technology

    2000-02-01

    part of the cell death execution machinery. Here we show that a correlation exists in breast cancer cells between caspase- dependent cleavage of the...inhibits its activity might allow us to specifically inhibit signaling pathways downstream of Pak and evaluate how the cell death process is affected. In...a biochemical approach screening for substrates and possible mediators of cell death signaling components via Pak kinases we identified a guanine

  2. Quercitrin attenuates osteoporosis in ovariectomized rats by regulating mitogen-activated protein kinase (MAPK) signaling pathways.

    PubMed

    Xing, Li-Zhi; Ni, Huai-Jun; Wang, Yu-Ling

    2017-03-13

    MAPK signaling pathways are crucial in regulating osteogenesis, a genetic disorder affecting the bones. Quercitrin, a type of flavonoid, is widely distributed in nature and involved in many pharmacological activities. But its osteoprotective functions and mechanism in osteoporosis are far from being understood clearly. In this paper, the MAPK upregulation was observed in the ovariectomy-induced bone loss. Quercitrin was found to downregulate MAPK signaling pathways and prevent the ovariectomy-induced deterioration of bone mineral density (BMD), trabecular microstructure, and bone mechanical characteristics. In this study, quercitrin was seen to prevent the progression of the postmenopausal osteoporosis among the rats, which may be mediated by the downregulated MAPK signaling pathways.

  3. A Requirement for ZAK Kinase Activity in Canonical TGF-β Signaling.

    PubMed

    Nyati, Shyam; Chator, Areeb; Schinske, Katerina; Gregg, Brandon S; Ross, Brian Dale; Rehemtulla, Alnawaz

    2016-12-01

    The sterile alpha motif and leucine zipper containing kinase ZAK (AZK, MLT, MLK7), is a MAPK-kinase kinase (MKKK). Like most MAPKKKs which are known to activate the c-Jun. amino-terminal kinase (JNK) pathway, ZAK has been shown to participate in the transduction of Transforming growth factor-β (TGF-β)-mediated non-canonical signaling. A role for ZAK in SMAD-dependent, canonical TGF-β signaling has not been previously appreciated. Using a combination of functional genomics and biochemical techniques, we demonstrate that ZAK regulates canonical TGFβRI/II signaling in lung and breast cancer cell lines and may serve as a key node in the regulation of TGFBR kinase activity. Remarkably, we demonstrate that siRNA mediated depletion of ZAK strongly inhibited TGF-β dependent SMAD2/3 activation and subsequent promoter activation (SMAD binding element driven luciferase expression; SBE4-Luc). A ZAK specific inhibitor (DHP-2), dose-dependently activated the bioluminescent TGFBR-kinase activity reporter (BTR), blocked TGF-β induced SMAD2/3 phosphorylation and SBE4-Luc activation and cancer cell-invasion. In aggregate, these findings identify a novel role for the ZAK kinase in canonical TGF-β signaling and an invasive cancer cell phenotype thus providing a novel target for TGF-β inhibition.

  4. Murine Polyomavirus Cell Surface Receptors Activate Distinct Signaling Pathways Required for Infection

    PubMed Central

    O’Hara, Samantha D.

    2016-01-01

    ABSTRACT Virus binding to the cell surface triggers an array of host responses, including activation of specific signaling pathways that facilitate steps in virus entry. Using mouse polyomavirus (MuPyV), we identified host signaling pathways activated upon virus binding to mouse embryonic fibroblasts (MEFs). Pathways activated by MuPyV included the phosphatidylinositol 3-kinase (PI3K), FAK/SRC, and mitogen-activated protein kinase (MAPK) pathways. Gangliosides and α4-integrin are required receptors for MuPyV infection. MuPyV binding to both gangliosides and the α4-integrin receptors was required for activation of the PI3K pathway; however, either receptor interaction alone was sufficient for activation of the MAPK pathway. Using small-molecule inhibitors, we confirmed that the PI3K and FAK/SRC pathways were required for MuPyV infection, while the MAPK pathway was dispensable. Mechanistically, the PI3K pathway was required for MuPyV endocytosis, while the FAK/SRC pathway enabled trafficking of MuPyV along microtubules. Thus, MuPyV interactions with specific cell surface receptors facilitate activation of signaling pathways required for virus entry and trafficking. Understanding how different viruses manipulate cell signaling pathways through interactions with host receptors could lead to the identification of new therapeutic targets for viral infection. PMID:27803182

  5. Tcra enhancer activation by inducible transcription factors downstream of pre-TCR signaling.

    PubMed

    del Blanco, Beatriz; García-Mariscal, Alberto; Wiest, David L; Hernández-Munain, Cristina

    2012-04-01

    The Tcra enhancer (Eα) is essential for pre-TCR-mediated activation of germline transcription and V(D)J recombination. Eα is considered an archetypical enhanceosome that acts through the functional synergy and cooperative binding of multiple transcription factors. Based on dimethylsulfate genomic footprinting experiments, there has been a long-standing paradox regarding Eα activation in the absence of differences in enhancer occupancy. Our data provide the molecular mechanism of Eα activation and an explanation of this paradox. We found that germline transcriptional activation of Tcra is dependent on constant phospholipase Cγ, as well as calcineurin- and MAPK/ERK-mediated signaling, indicating that inducible transcription factors are crucially involved. NFAT, AP-1, and early growth response factor 1, together with CREB-binding protein/p300 coactivators, bind to Eα as part of an active enhanceosome assembled during pre-TCR signaling. We favor a scenario in which the binding of lymphoid-restricted and constitutive transcription factors to Eα prior to its activation forms a regulatory scaffold to recruit factors induced by pre-TCR signaling. Thus, the combinatorial assembly of tissue- and signal-specific transcription factors dictates the Eα function. This mechanism for enhancer activation may represent a general paradigm in tissue-restricted and stimulus-responsive gene regulation.

  6. Potential Function of Exogenous Vimentin on the Activation of Wnt Signaling Pathway in Cancer Cells

    PubMed Central

    Satelli, Arun; Hu, Jiemiao; Xia, Xueqing; Li, Shulin

    2016-01-01

    Cancer cell signaling, growth, morphology, proliferation and tumorigenic potential are largely depending on the signaling molecules present naturally in the tumor microenvironment and the identification of key molecules that drive the tumor progression is critical for the development of new modalities for the prevention of tumor progression. High concentrations of vimentin in the blood of cancer patients have been reported, however the function of blood circulating vimentin remains unknown. Here, we investigated the functional role of exogenously supplemented vimentin on colon cancer cells and examined the Wnt Signaling activation and cancer cell invasion. Vimentin when supplemented to the cancer cells remained bound to the surface of the cancer cells. Furthermore, bound vimentin activates Wnt signaling pathway as detectable by increased β-catenin accumulation in the nucleus with concomitant activation of β-catenin-dependent transcription of Wnt signaling downstream targets. Functionally, there was an increase in the rate of cellular invasion in these cancer cells upon binding with vimentin. Our results thus suggest that free vimentin in the tumor microenvironment acts as a positive regulator of the β-catenin signaling pathway, thus providing a basis for cancer invasive properties. PMID:27698922

  7. Constitutive activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor κB signaling in glioblastoma cancer stem cells regulates the Notch pathway.

    PubMed

    Garner, Jo Meagan; Fan, Meiyun; Yang, Chuan He; Du, Ziyun; Sims, Michelle; Davidoff, Andrew M; Pfeffer, Lawrence M

    2013-09-06

    Malignant gliomas are locally aggressive, highly vascular tumors that have a dismal prognosis, and present therapies provide little improvement in the disease course and outcome. Many types of malignancies, including glioblastoma, originate from a population of cancer stem cells (CSCs) that are able to initiate and maintain tumors. Although CSCs only represent a small fraction of cells within a tumor, their high tumor-initiating capacity and therapeutic resistance drives tumorigenesis. Therefore, it is imperative to identify pathways associated with CSCs to devise strategies to selectively target them. In this study, we describe a novel relationship between glioblastoma CSCs and the Notch pathway, which involves the constitutive activation of STAT3 and NF-κB signaling. Glioma CSCs were isolated and maintained in vitro using an adherent culture system, and the biological properties were compared with the traditional cultures of CSCs grown as multicellular spheres under nonadherent culture conditions. Interestingly, both adherent and spheroid glioma CSCs show constitutive activation of the STAT3/NF-κB signaling pathway and up-regulation of STAT3- and NF-κB-dependent genes. Gene expression profiling also identified components of the Notch pathway as being deregulated in glioma CSCs, and the deregulated expression of these genes was sensitive to treatment with STAT3 and NF-κB inhibitors. This finding is particularly important because Notch signaling appears to play a key role in CSCs in a variety of cancers and controls cell fate determination, survival, proliferation, and the maintenance of stem cells. The constitutive activation of STAT3 and NF-κB signaling pathways that leads to the regulation of Notch pathway genes in glioma CSCs identifies novel therapeutic targets for the treatment of glioma.

  8. Activation of Melatonin Signaling Promotes β-Cell Survival and Function.

    PubMed

    Costes, Safia; Boss, Marti; Thomas, Anthony P; Matveyenko, Aleksey V

    2015-05-01

    Type 2 diabetes mellitus (T2DM) is characterized by pancreatic islet failure due to loss of β-cell secretory function and mass. Studies have identified a link between a variance in the gene encoding melatonin (MT) receptor 2, T2DM, and impaired insulin secretion. This genetic linkage raises the question whether MT signaling plays a role in regulation of β-cell function and survival in T2DM. To address this postulate, we used INS 832/13 cells to test whether activation of MT signaling attenuates proteotoxicity-induced β-cell apoptosis and through which molecular mechanism. We also used nondiabetic and T2DM human islets to test the potential of MT signaling to attenuate deleterious effects of glucotoxicity and T2DM on β-cell function. MT signaling in β-cells (with duration designed to mimic typical nightly exposure) significantly enhanced activation of the cAMP-dependent signal transduction pathway and attenuated proteotoxicity-induced β-cell apoptosis evidenced by reduced caspase-3 cleavage (∼40%), decreased activation of stress-activated protein kinase/Jun-amino-terminal kinase (∼50%) and diminished oxidative stress response. Activation of MT signaling in human islets was shown to restore glucose-stimulated insulin secretion in islets exposed to chronic hyperglycemia as well as in T2DM islets. Our data suggest that β-cell MT signaling is important for the regulation of β-cell survival and function and implies a preventative and therapeutic potential for preservation of β-cell mass and function in T2DM.

  9. Task Control Signals in Pediatric Tourette Syndrome Show Evidence of Immature and Anomalous Functional Activity

    PubMed Central

    Church, Jessica A.; Wenger, Kristin K.; Dosenbach, Nico U. F.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.

    2009-01-01

    Tourette Syndrome (TS) is a pediatric movement disorder that may affect control signaling in the brain. Previous work has proposed a dual-networks architecture of control processing involving a task-maintenance network and an adaptive control network (Dosenbach et al., 2008). A prior resting-state functional connectivity MRI (rs-fcMRI) analysis in TS has revealed functional immaturity in both putative control networks, with “anomalous” correlations (i.e., correlations outside the typical developmental range) limited to the adaptive control network (Church et al., 2009). The present study used functional MRI (fMRI) to study brain activity related to adaptive control (by studying start-cues signals), and to task-maintenance (by studying signals sustained across a task set). Two hypotheses from the previous rs-fcMRI results were tested. First, adaptive control (i.e., start-cue) activity will be altered in TS, including activity inconsistent with typical development (“anomalous”). Second, group differences found in task-maintenance (i.e., sustained) activity will be consistent with functional immaturity in TS. We examined regions found through a direct comparison of adolescents with and without TS, as well as regions derived from a previous investigation that showed differences between unaffected children and adults. The TS group showed decreased start-cue signal magnitude in regions where start-cue activity is unchanged over typical development, consistent with anomalous adaptive control. The TS group also had higher magnitude sustained signals in frontal cortex regions that overlapped with regions showing differences over typical development, consistent with immature task-maintenance in TS. The results demonstrate task-related fMRI signal differences anticipated by the atypical functional connectivity found previously in adolescents with TS, strengthening the evidence for functional immaturity and anomalous signaling in control networks in adolescents with TS

  10. Studies on Sonar Clutter and Reverberation

    DTIC Science & Technology

    2012-09-30

    ABSTRACT SAR 18. NUMBER OF PAGES 8 19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b. ABSTRACT unclassified c. THIS PAGE unclassified... Bistatic signal excess calculations over variable bottom topography using adiabatic normal modes, In Nielsen et al. [13], pages 97–104. [15] M...Results, Kos, Greece, June 2011, pages 657-664, (Invited). [20] D. A. Abraham and J. R. Preston, “Statistical analysis of monostatic and bistatic

  11. Methylglyoxal activates the target of rapamycin complex 2-protein kinase C signaling pathway in Saccharomyces cerevisiae.

    PubMed

    Nomura, Wataru; Inoue, Yoshiharu

    2015-04-01

    Methylglyoxal is a typical 2-oxoaldehyde derived from glycolysis. We show here that methylglyoxal activates the Pkc1-Mpk1 mitogen-activated protein (MAP) kinase cascade in a target of rapamycin complex 2 (TORC2)-dependent manner in the budding yeast Saccharomyces cerevisiae. We demonstrate that TORC2 phosphorylates Pkc1 at Thr(1125) and Ser(1143). Methylglyoxal enhanced the phosphorylation of Pkc1 at Ser(1143), which transmitted the signal to the downstream Mpk1 MAP kinase cascade. We found that the phosphorylation status of Pkc1(T1125) affected the phosphorylation of Pkc1 at Ser(1143), in addition to its protein levels. Methylglyoxal activated mammalian TORC2 signaling, which, in turn, phosphorylated Akt at Ser(473). Our results suggest that methylglyoxal is a conserved initiator of TORC2 signaling among eukaryotes.

  12. Methylglyoxal Activates the Target of Rapamycin Complex 2-Protein Kinase C Signaling Pathway in Saccharomyces cerevisiae

    PubMed Central

    Nomura, Wataru

    2015-01-01

    Methylglyoxal is a typical 2-oxoaldehyde derived from glycolysis. We show here that methylglyoxal activates the Pkc1-Mpk1 mitogen-activated protein (MAP) kinase cascade in a target of rapamycin complex 2 (TORC2)-dependent manner in the budding yeast Saccharomyces cerevisiae. We demonstrate that TORC2 phosphorylates Pkc1 at Thr1125 and Ser1143. Methylglyoxal enhanced the phosphorylation of Pkc1 at Ser1143, which transmitted the signal to the downstream Mpk1 MAP kinase cascade. We found that the phosphorylation status of Pkc1T1125 affected the phosphorylation of Pkc1 at Ser1143, in addition to its protein levels. Methylglyoxal activated mammalian TORC2 signaling, which, in turn, phosphorylated Akt at Ser473. Our results suggest that methylglyoxal is a conserved initiator of TORC2 signaling among eukaryotes. PMID:25624345

  13. Interrogating the signaling dynamics of T cell activation with quantum dots

    NASA Astrophysics Data System (ADS)

    Warnement, Michael R.; Faley, Shannon L.; Wikswo, John P.; Rosenthal, Sandra J.

    2006-02-01

    We report the use of antibody-conjugated quantum dots (QDs) to monitor the expression dynamics of the membrane bound cytokine receptor interleukin-2 receptor-α (IL-2Rα) throughout the course of Jurkat T cell activation. Maximal receptor expression is observed 32-48 hours after activation, followed by a sharp decrease subsequent to 48 hours consistent with IL-2R internalization. Fluorescence microscopy, ELISA, and FACS analyses were used to verify controlled activation and specificity of QD labeling. Additionally, confocal microscopy demonstrated receptor internalization subsequent to expression and QD labeling. Antibody-conjugated QDs provide a convenient means to rapidly determine cell state and interrogate end products of cell signaling pathways. Interrogation of other signaling pathways can eventually be carried out in a similar manner upon identification of relevant membrane associated receptors. Ultimately, the multiplexing capabilities of QDs will allow the examination of several signaling pathways simultaneously and aid in toxin detection and discrimination.

  14. Phagocyte respiratory burst activates macrophage erythropoietin signalling to promote acute inflammation resolution

    PubMed Central

    Luo, Bangwei; Wang, Jinsong; Liu, Zongwei; Shen, Zigang; Shi, Rongchen; Liu, Yu-Qi; Liu, Yu; Jiang, Man; Wu, Yuzhang; Zhang, Zhiren

    2016-01-01

    Inflammation resolution is an active process, the failure of which causes uncontrolled inflammation which underlies many chronic diseases. Therefore, endogenous pathways that regulate inflammation resolution are fundamental and of wide interest. Here, we demonstrate that phagocyte respiratory burst-induced hypoxia activates macrophage erythropoietin signalling to promote acute inflammation resolution. This signalling is activated following acute but not chronic inflammation. Pharmacological or genetical inhibition of the respiratory burst suppresses hypoxia and macrophage erythropoietin signalling. Macrophage-specific erythropoietin receptor-deficient mice and chronic granulomatous disease (CGD) mice, which lack the capacity for respiratory burst, display impaired inflammation resolution, and exogenous erythropoietin enhances this resolution in WT and CGD mice. Mechanistically, erythropoietin increases macrophage engulfment of apoptotic neutrophils via PPARγ, promotes macrophage removal of debris and enhances macrophage migration to draining lymph nodes. Together, our results provide evidences of an endogenous pathway that regulates inflammation resolution, with important implications for treating inflammatory conditions. PMID:27397585

  15. Highly Parallel Modern Signal Processing.

    DTIC Science & Technology

    1982-02-28

    looked at the application of these techniques to systems with coherent speckle noise, such as synthetic aperature (SAR) imagery, coherent sonar and...pprtitioned matrix inversion , comput;atio-n o"f crossambigul ty fun~ctions, formation of outer prCdu1cL tAand skewed outer products, and multiplication of...operations are multiplication, inversion , and L-U decomposition. In signal processing such operations can be found in adaptive filtering, data

  16. Signalling pathways induced by protease-activated receptors and integrins in T cells.

    PubMed

    Bar-Shavit, Rachel; Maoz, Miriam; Yongjun, Yin; Groysman, Maya; Dekel, Idit; Katzav, Shulamit

    2002-01-01

    Recent characterization of the thrombin receptor indicates that it plays a role in T-cell signalling pathways. However, little is known regarding the signalling events following stimulation of additional members of the protease-activated receptor (PAR) family, i.e. PAR2 and PAR3. Most of the postligand cascades are largely unknown. Here, we illustrate that in Jurkat T-leukaemic cells, activation of PAR1, PAR2 and PAR3 induce tyrosine phosphorylation of Vav1. This response was impaired in Jurkat T cells deficient in p56lck (JCaM1.6). Activation of PARs also led to an increase in tyrosine phosphorylation of ZAP-70 and SLP-76, two key proteins in T-cell receptor (TCR) signalling. We also demonstrated that p56lck is meaningful for integrin signalling. Thus, JCaM1.6 cells exhibited a marked reduction in their adherence to fibronectin-coated plates, as compared to the level of adherence of Jurkat T cells. While the phosphorylation of Vav1 in T cells is augmented following adhesion, no additional increase was noted following treatment of the adhered cells with PARs. Altogether, we have identified key components in the postligand-signalling cascade of PARs and integrins. Furthermore, we have identified Lck as a critical and possibly upstream component of PAR-induced Vav1 phosphorylation, as well as integrin activation, in Jurkat T cells.

  17. Eviprostat activates cAMP signaling pathway and suppresses bladder smooth muscle cell proliferation.

    PubMed

    Li, Kai; Yao, Jian; Chi, Yuan; Sawada, Norifumi; Araki, Isao; Kitamura, Masanori; Takeda, Masayuki

    2013-06-06

    Eviprostat is a popular phytotherapeutic agent for the treatment of lower urinary tract symptoms (LUTS). At present, the signaling mechanisms underlying its therapeutic effects are still poorly understood. Given that cAMP has been reported to suppress cell hyperplasia and hypertrophy in various pathological situations, we asked whether the effect of Eviprostat could be ascribed to the activation of the cAMP signaling pathway. In the study, exposure of cAMP response element (CRE)-secreted alkaline phosphatase (SEAP) (CRE-SEAP)-reporter cells to Eviprostat elevated SEAP secretion, which was associated with an increased phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and cAMP-response element-binding protein (CREB), as well as enhanced expression of CRE-regulated protein connexin43, indicating an activation of the cAMP signaling pathway. Consistent with these observations, Eviprostat-induced expression of Cx43 was abolished in the presence of adenylyl cyclase inhibitor SQ22536 or PKA inhibitor H89, whereas it was mimicked by adenylyl cyclase activator, forskolin. Further analysis demonstrated that Eviprostat significantly potentiated the effect of phosphodiesterase 3 (PDE3) inhibitor, but not that of PDE4 inhibitor, on CRE activation. Moreover, Eviprostat suppressed PDGF-induced activation of ERK and Akt and inhibited cell proliferation and hillock formation in both mesangial cells and bladder smooth muscle cells. Collectively, activation of the cAMP signaling pathway could be an important mechanism by which Eviprostat exerts its therapeutic effects for LUTS.

  18. A role for Raptor phosphorylation in the mechanical activation of mTOR signaling.

    PubMed

    Frey, John W; Jacobs, Brittany L; Goodman, Craig A; Hornberger, Troy A

    2014-02-01

    The activation of mTOR signaling is necessary for mechanically-induced changes in skeletal muscle mass, but the mechanisms that regulate the mechanical activation of mTOR signaling remain poorly defined. In this study, we set out to determine if changes in the phosphorylation of Raptor contribute to the mechanical activation of mTOR. To accomplish this goal, mouse skeletal muscles were subjected to mechanical stimulation via a bout of eccentric contractions (EC). Using mass spectrometry and Western blot analysis, we found that ECs induced an increase in Raptor S696, T706, and S863 phosphorylation, and this effect was not inhibited by rapamycin. This observation suggested that changes in Raptor phosphorylation might be an upstream event in the pathway through which mechanical stimuli activate mTOR. To test this, we employed a phospho-defective mutant of Raptor (S696A/T706A/S863A) and found that the EC-induced activation of mTOR signaling was significantly blunted in muscles expressing this mutant. Furthermore, mutation of the three phosphorylation sites altered the interactions of Raptor with PRAS40 and p70(S6k), and it also prevented the EC-induced dissociation of Raptor from p70(S6k). Combined, these results suggest that changes in the phosphorylation of Raptor play an important role in the pathway through which mechanical stimuli activate mTOR signaling.

  19. The lack of autophagy triggers precocious activation of Notch signaling during Drosophila oogenesis

    PubMed Central

    2012-01-01

    Background The proper balance of autophagy, a lysosome-mediated degradation process, is indispensable for oogenesis in Drosophila. We recently demonstrated that egg development depends on autophagy in the somatic follicle cells (FC), but not in the germline cells (GCs). However, the lack of autophagy only affects oogenesis when FCs are autophagy-deficient but GCs are wild type, indicating that a dysfunctional signaling between soma and germline may be responsible for the oogenesis defects. Thus, autophagy could play an essential role in modulating signal transduction pathways during egg development. Results Here, we provide further evidence for the necessity of autophagy during oogenesis and demonstrate that autophagy is especially required in subsets of FCs. Generation of autophagy-deficient FCs leads to a wide range of phenotypes that are similar to mutants with defects in the classical cell-cell signaling pathways in the ovary. Interestingly, we observe that loss of autophagy leads to a precocious activation of the Notch pathway in the FCs as monitored by the expression of Cut and Hindsight, two downstream effectors of Notch signaling. Conclusion Our findings point to an unexpected function for autophagy in the modulation of the Notch signaling pathway during Drosophila oogenesis and suggest a function for autophagy in proper receptor activation. Egg development is affected by an imbalance of autophagy between signal sending (germline) and signal receiving cell (FC), thus the lack of autophagy in the germline is likely to decrease the amount of active ligand and accordingly compensates for increased signaling in autophagy-defective follicle cells. PMID:23217079

  20. Voltage-gated Na+ Channel Activity Increases Colon Cancer Transcriptional Activity and Invasion Via Persistent MAPK Signaling.

    PubMed

    House, Carrie D; Wang, Bi-Dar; Ceniccola, Kristin; Williams, Russell; Simaan, May; Olender, Jacqueline; Patel, Vyomesh; Baptista-Hon, Daniel T; Annunziata, Christina M; Gutkind, J Silvio; Hales, Tim G; Lee, Norman H

    2015-06-22

    Functional expression of voltage-gated Na(+) channels (VGSCs) has been demonstrated in multiple cancer cell types where channel activity induces invasive activity. The signaling mechanisms by which VGSCs promote oncogenesis remain poorly understood. We explored the signal transduction process critical to VGSC-mediated invasion on the basis of reports linking channel activity to gene expression changes in excitable cells. Coincidentally, many genes transcriptionally regulated by the SCN5A isoform in colon cancer have an over-representation of cis-acting sites for transcription factors phosphorylated by ERK1/2 MAPK. We hypothesized that VGSC activity promotes MAPK activation to induce transcriptional changes in invasion-related genes. Using pharmacological inhibitors/activators and siRNA-mediated gene knockdowns, we correlated channel activity with Rap1-dependent persistent MAPK activation in the SW620 human colon cancer cell line. We further demonstrated that VGSC activity induces downstream changes in invasion-related gene expression via a PKA/ERK/c-JUN/ELK-1/ETS-1 transcriptional pathway. This is the first study illustrating a molecular mechanism linking functional activity of VGSCs to transcriptional activation of invasion-related genes.

  1. Voltage-gated Na+ Channel Activity Increases Colon Cancer Transcriptional Activity and Invasion Via Persistent MAPK Signaling

    NASA Astrophysics Data System (ADS)

    House, Carrie D.; Wang, Bi-Dar; Ceniccola, Kristin; Williams, Russell; Simaan, May; Olender, Jacqueline; Patel, Vyomesh; Baptista-Hon, Daniel T.; Annunziata, Christina M.; Silvio Gutkind, J.; Hales, Tim G.; Lee, Norman H.

    2015-06-01

    Functional expression of voltage-gated Na+ channels (VGSCs) has been demonstrated in multiple cancer cell types where channel activity induces invasive activity. The signaling mechanisms by which VGSCs promote oncogenesis remain poorly understood. We explored the signal transduction process critical to VGSC-mediated invasion on the basis of reports linking channel activity to gene expression changes in excitable cells. Coincidentally, many genes transcriptionally regulated by the SCN5A isoform in colon cancer have an over-representation of cis-acting sites for transcription factors phosphorylated by ERK1/2 MAPK. We hypothesized that VGSC activity promotes MAPK activation to induce transcriptional changes in invasion-related genes. Using pharmacological inhibitors/activators and siRNA-mediated gene knockdowns, we correlated channel activity with Rap1-dependent persistent MAPK activation in the SW620 human colon cancer cell line. We further demonstrated that VGSC activity induces downstream changes in invasion-related gene expression via a PKA/ERK/c-JUN/ELK-1/ETS-1 transcriptional pathway. This is the first study illustrating a molecular mechanism linking functional activity of VGSCs to transcriptional activation of invasion-related genes.

  2. Digital image processing techniques for enhancement and classification of SeaMARC II side scan sonar imagery

    NASA Astrophysics Data System (ADS)

    Reed, Thomas Beckett, IV; Hussong, Donald

    1989-06-01

    The recent growth in the production rate of digital side scan sonar images, coupled with the rapid expansion of systematic seafloor exploration programs, has created a need for fast and quantitative means of processing seafloor imagery. Computer-aided analytical techniques fill this need. A number of numerical techniques used to enhance and classify imagery produced by SeaMARC II, a long-range combination side scan sonar, and bathymetric seafloor mapping system are documented. Three categories of techniques are presented: (1) preprocessing corrections (radiometric and geometric), (2) feature extraction, and (3) image segmentation and classification. An introduction to the concept of "feature vectors" is provided, along with an explanation of the method of evaluation of a texture feature vector based upon gray-level co-occurrence matrices (GLCM). An alternative to the a priori texel (texture element) subdivision of images is presented in the form of region growing and texture analysis (REGATA). This routine provides a texture map of spatial resolution superior to that obtainable with arbitrarily assigned texel boundaries and minimizes the possibility of mixed texture signals due to the combination of two or more textures in an arbitrarily assigned texel. Computer classification of these textural features extracted via the GLCM technique results in transformation of images into maps of image texture. These maps may either be interpreted in terms of the theoretical relationships shown between texture signatures and wavelength or converted to geologic maps by correlation of texture signatures with ground truth data. These techniques are applied to SeaMARC II side scan sonar imagery from a variety of geologic environments, including lithified and nonlithified sedimentary formations, volcanic and sedimentary debris flows, and crystalline basaltic outcrops. Application of the above processing steps provided not only superior images for both subjective and quantitative

  3. An alternative mode of CD43 signal transduction activates pro-survival pathways of T lymphocytes.

    PubMed

    Bravo-Adame, Maria Elena; Vera-Estrella, Rosario; Barkla, Bronwyn J; Martínez-Campos, Cecilia; Flores-Alcantar, Angel; Ocelotl-Oviedo, Jose Pablo; Pedraza-Alva, Gustavo; Rosenstein, Yvonne

    2017-01-01

    CD43 is one of the most abundant co-stimulatory molecules on a T-cell surface; it transduces activation signals through its cytoplasmic domain, contributing to modulation of the outcome of T-cell responses. The aim of this study was to uncover new signalling pathways regulated by this sialomucin. Analysis of changes in protein abundance allowed us to identify pyruvate kinase isozyme M2 (PKM2), an enzyme of the glycolytic pathway, as an element potentially participating in the signalling cascade resulting from the engagement of CD43 and the T-cell receptor (TCR). We found that the glycolytic activity of this enzyme was not significantly increased in response to TCR+CD43 co-stimulation, but that PKM2 was tyrosine phosphorylated, suggesting that it was performing moonlight functions. We report that phosphorylation of both Y(105) of PKM2 and of Y(705) of signal transducer and activator of transcription 3 was induced in response to TCR+CD43 co-stimulation, resulting in activation of the mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) pathway. ERK5 and the cAMP response element binding protein (CREB) were activated, and c-Myc and nuclear factor-κB (p65) nuclear localization, as well as Bad phosphorylation, were augmented. Consistent with this, expression of human CD43 in a murine T-cell hybridoma favoured cell survival. Altogether, our data highlight novel signalling pathways for the CD43 molecule in T lymphocytes, and underscore a role for CD43 in promoting cell survival through non-glycolytic functions of metabolic enzymes.

  4. Range compensation for backscattering measurements in the difference-frequency nearfield of a parametric sonar.

    PubMed

    Foote, Kenneth G

    2012-05-01

    Measurement of acoustic backscattering properties of targets requires removal of the range dependence of echoes. This process is called range compensation. For conventional sonars making measurements in the transducer farfield, the compensation removes effects of geometrical spreading and absorption. For parametric sonars consisting of a parametric acoustic transmitter and a conventional-sonar receiver, two additional range dependences require compensation when making measurements in the nonlinearly generated difference-frequency nearfield: an apparently increasing source level and a changing beamwidth. General expressions are derived for range compensation functions in the difference-frequency nearfield of parametric sonars. These are evaluated numerically for a parametric sonar whose difference-frequency band, effectively 1-6 kHz, is being used to observe Atlantic herring (Clupea harengus) in situ. Range compensation functions for this sonar are compared with corresponding functions for conventional sonars for the cases of single and multiple scatterers. Dependences of these range compensation functions on the parametric sonar transducer shape, size, acoustic power density, and hydrography are investigated. Parametric range compensation functions, when applied with calibration data, will enable difference-frequency echoes to be expressed in physical units of volume backscattering, and backscattering spectra, including fish-swimbladder-resonances, to be analyzed.

  5. Quantifying Effects of Mid-Frequency Sonar Transmissions on Fish and Whale

    DTIC Science & Technology

    2010-09-30

    different cruises with different vessels and TOPAS parametric sonars. The first calibration trial was conducted with R/V “G. O. Sars” in the Sørfolla fjord ...sonar during the calibration exercise with R/V “G. O. Sars” in Sørfolla fjord on 10 December 2008 has been addressed in a preliminary study (Foote et al

  6. Activation of MAPK/ERK signaling by Burkholderia pseudomallei cycle inhibiting factor (Cif)

    PubMed Central

    Ng, Mei Ying; Wang, Mei; Casey, Patrick J.; Gan, Yunn-Hwen; Hagen, Thilo

    2017-01-01

    Cycle inhibiting factors (Cifs) are virulence proteins secreted by the type III secretion system of some Gram-negative pathogenic bacteria including Burkholderia pseudomallei. Cif is known to function to deamidate Nedd8, leading to inhibition of Cullin E3 ubiquitin ligases (CRL) and consequently induction of cell cycle arrest. Here we show that Cif can function as a potent activator of MAPK/ERK signaling without significant activation of other signaling pathways downstream of receptor tyrosine kinases. Importantly, we found that the ability of Cif to activate ERK is dependent on its deamidase activity, but independent of Cullin E3 ligase inhibition. This suggests that apart from Nedd8, other cellular targets of Cif-dependent deamidation exist. We provide evidence that the mechanism involved in Cif-mediated ERK activation is dependent on recruitment of the Grb2-SOS1 complex to the plasma membrane. Further investigation revealed that Cif appears to modify the phosphorylation status of SOS1 in a region containing the CDC25-H and proline-rich domains. It is known that prolonged Cullin E3 ligase inhibition leads to cellular apoptosis. Therefore, we hypothesize that ERK activation is an important mechanism to counter the pro-apoptotic effects of Cif. Indeed, we show that Cif dependent ERK activation promotes phosphorylation of the proapoptotic protein Bim, thereby potentially conferring a pro-survival signal. In summary, we identified a novel deamidation-dependent mechanism of action of the B. pseudomallei virulence factor Cif/CHBP to activate MAPK/ERK signaling. Our study demonstrates that bacterial proteins such as Cif can serve as useful molecular tools to uncover novel aspects of mammalian signaling pathways. PMID:28166272

  7. Inhibition of a signaling pathway in cardiac muscle cells by active mitogen-activated protein kinase kinase.

    PubMed Central

    Thorburn, J; Carlson, M; Mansour, S J; Chien, K R; Ahn, N G; Thorburn, A

    1995-01-01

    Signaling via the Ras pathway involves sequential activation of Ras, Raf-1, mitogen-activated protein kinase kinase (MKK), and the extracellular signal-regulated (ERK) group of mitogen-activated protein (MAP) kinases. Expression from the c-Fos, atrial natriuretic factor (ANF), and myosin light chain-2 (MLC-2) promoters during phenylephrine-induced cardiac muscle cell hypertrophy requires activation of this pathway. Furthermore, constitutively active Ras or Raf-1 can mimic the action of phenylephrine in inducing expression from these promoters. In this study, we tested whether constitutively active MKK, the molecule immediately downstream of Raf, was sufficient to induce expression. Expression of constitutively active MKK induce ERK2 kinase activity and caused expression from the c-Fos promoter, but did not significantly activate expression of reporter genes under the control of either the ANF or MLC-2 promoters. Expression of CL100, a phosphatase that inactivates ERKs, prevented expression from all of the promoters. Taken together, these data suggest that ERK activation is required for expression from the Fos, ANF, and MLC-2 promoters but MKK and ERK activation is sufficient for expression only from the Fos promoter. Constitutively active MKK synergized with phenylephrine to increase expression from a c-Fos- or an AP1-driven reporter. However, active MKK inhibited phenylephrine- and Raf-1-induced expression from the ANF and MLC-2 promoters. A DNA sequence in the MLC-2 promoter that is a target for inhibition by active MKK, but not CL100, was mapped to a previously characterized DNA element (HF1) that is responsible for cardiac specificity. Thus, activation of cardiac gene expression during phenylephrine-induced hypertrophy requires ERK activation but constitutive activation by MKK can inhibit expression by targeting a DNA element that controls the cardiac specificity of gene expression. PMID:8589450

  8. CD5-CK2 Signaling Modulates Erk Activation and Thymocyte Survival

    PubMed Central

    Mier-Aguilar, Carlos A.; Cashman, Kevin S.; Raman, Chander; Soldevila, Gloria

    2016-01-01

    CD5 is well recognized for its importance in thymic selection. Although this property of CD5 has been attributed to its ITIM-domain dependent regulation of TCR-signal strength, the mechanism has not been established. A second major signaling domain within the cytoplasmic tail of CD5 is a CK2 binding/activation domain (CD5-CK2BD). Using a gene-targeted mouse in which the CD5-CK2BD is selectively ablated (CD5-ΔCK2BD), we determined that loss of function of CD5-CK2 signaling in a MHC-II selecting TCR transgenic (OT-II) mouse resulted in decrease in double positive (DP) thymocytes, which correlated with enhanced apoptosis. Remarkably, DP cells expressing high levels of CD5 and CD69 and single positive (CD4+SP) thymocytes were increased in CD5-ΔCK2BD mice indicating that CD5-CK2 signaling regulates positive selection and promotes survival. Consistent with this possibility, we determined that the activation and nuclear localization of ERK as well as apoptosis was greater in thymic populations from OTII CD5-ΔCK2BD mice than OTII CD5-WT mice following injection of OVA323-339-peptide. The mobilization of Ca2+, an early event of TCR activation, was not altered by the loss of CD5-CK2 signaling. Collectively, these data demonstrate that the CD5-CK2 signaling axis regulates positive selection by modulating activation of ERK and promoting survival independent of proximal TCR signals. PMID:28030587

  9. Luminance and chromatic signals interact differently with melanopsin activation to control the pupil light response

    PubMed Central

    Barrionuevo, Pablo A.; Cao, Dingcai

    2016-01-01

    Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin. These cells receive afferent inputs from rods and cones, which provide inputs to the postreceptoral visual pathways. It is unknown, however, how melanopsin activation is integrated with postreceptoral signals to control the pupillary light reflex. This study reports human flicker pupillary responses measured using stimuli generated with a five-primary photostimulator that selectively modulated melanopsin, rod, S-, M-, and L-cone excitations in isolation, or in combination to produce postreceptoral signals. We first analyzed the light adaptation behavior of melanopsin activation and rod and cones signals. Second, we determined how melanopsin is integrated with postreceptoral signals by testing with cone luminance, chromatic blue-yellow, and chromatic red-green stimuli that were processed by magnocellular (MC), koniocellular (KC), and parvocellular (PC) pathways, respectively. A combined rod and melanopsin response was also measured. The relative phase of the postreceptoral signals was varied with respect to the melanopsin phase. The results showed that light adaptation behavior for all conditions was weaker than typical Weber adaptation. Melanopsin activation combined linearly with luminance, S-cone, and rod inputs, suggesting the locus of integration with MC and KC signals was retinal. The melanopsin contribution to phasic pupil responses was lower than luminance contributions, but much higher than S-cone contributions. Chromatic red-green modulation interacted with melanopsin activation nonlinearly as described by a “winner-takes-all” process, suggesting the integration with PC signals might be mediated by a postretinal site. PMID:27690169

  10. [Combination of two signals of danger--a principal cause of activation of chronic inflammatory processes].

    PubMed

    Lebedev, K A

    2012-01-01

    Chronic inflammatory processes have long current during which there is a change of remission by an aggravation of disease. Until recently was considered, that occurrence and activation of chronic inflammatory process is caused by one signal of danger. Most often it are served with microorganisms. The sum of our end literary data shows that activation is connected with accumulation in the center of an inflammation of macrophages and their hyperactivation as a result of action of two signals of danger--microorganisms and xenobiotics.

  11. In the newborn hippocampus, neurotrophin-dependent survival requires spontaneous activity and integrin signaling

    PubMed Central

    Murase, Sachiko; Owens, David F.; McKay, Ronald D.

    2012-01-01

    The nervous system develops through a program that first produces neurons in excess and then eliminates as many as half in a specific period of early post-natal life. Neurotrophins are widely thought to regulate neuronal survival but this role has not been clearly defined in the central nervous system. Here we show that neurotrophins promote survival of young neurons by promoting spontaneous activity. Survival of hippocampal neurons in neonatal rat requires spontaneous activity that depends on the excitatory action of γ-aminobutyric acid (GABA). Neurotrophins facilitate recruitment of cultured neurons into active networks, and it is this activity, combined with integrin receptor signaling, that controls neuronal survival. In vivo, neurotrophins require integrin signaling to control neuron number. These data are the first to link the early excitatory action of GABA to the developmental death period and to assign an essential role for activity in neurotrophin-mediated survival that establishes appropriate networks. PMID:21613492

  12. Aurora A drives early signalling and vesicle dynamics during T-cell activation.

    PubMed

    Blas-Rus, Noelia; Bustos-Morán, Eugenio; Pérez de Castro, Ignacio; de Cárcer, Guillermo; Borroto, Aldo; Camafeita, Emilio; Jorge, Inmaculada; Vázquez, Jesús; Alarcón, Balbino; Malumbres, Marcos; Martín-Cófreces, Noa B; Sánchez-Madrid, Francisco

    2016-04-19

    Aurora A is a serine/threonine kinase that contributes to the progression of mitosis by inducing microtubule nucleation. Here we have identified an unexpected role for Aurora A kinase in antigen-driven T-cell activation. We find that Aurora A is phosphorylated at the immunological synapse (IS) during TCR-driven cell contact. Inhibition of Aurora A with pharmacological agents or genetic deletion in human or mouse T cells severely disrupts the dynamics of microtubules and CD3ζ-bearing vesicles at the IS. The absence of Aurora A activity also impairs the activation of early signalling molecules downstream of the TCR and the expression of IL-2, CD25 and CD69. Aurora A inhibition causes delocalized clustering of Lck at the IS and decreases phosphorylation levels of tyrosine kinase Lck, thus indicating Aurora A is required for maintaining Lck active. These findings implicate Aurora A in the propagation of the TCR activation signal.

  13. Aurora A drives early signalling and vesicle dynamics during T-cell activation

    PubMed Central

    Blas-Rus, Noelia; Bustos-Morán, Eugenio; Pérez de Castro, Ignacio; de Cárcer, Guillermo; Borroto, Aldo; Camafeita, Emilio; Jorge, Inmaculada; Vázquez, Jesús; Alarcón, Balbino; Malumbres, Marcos; Martín-Cófreces, Noa B.; Sánchez-Madrid, Francisco

    2016-01-01

    Aurora A is a serine/threonine kinase that contributes to the progression of mitosis by inducing microtubule nucleation. Here we have identified an unexpected role for Aurora A kinase in antigen-driven T-cell activation. We find that Aurora A is phosphorylated at the immunological synapse (IS) during TCR-driven cell contact. Inhibition of Aurora A with pharmacological agents or genetic deletion in human or mouse T cells severely disrupts the dynamics of microtubules and CD3ζ-bearing vesicles at the IS. The absence of Aurora A activity also impairs the activation of early signalling molecules downstream of the TCR and the expression of IL-2, CD25 and CD69. Aurora A inhibition causes delocalized clustering of Lck at the IS and decreases phosphorylation levels of tyrosine kinase Lck, thus indicating Aurora A is required for maintaining Lck active. These findings implicate Aurora A in the propagation of the TCR activation signal. PMID:27091106

  14. Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans*

    PubMed Central

    Andrusiak, Matthew G.; Jin, Yishi

    2016-01-01

    Stress-associated p38 and JNK mitogen-activated protein (MAP) kinase signaling cascades trigger specific cellular responses and are involved in multiple disease states. At the root of MAP kinase signaling complexity is the differential use of common components on a context-specific basis. The roundworm Caenorhabditis elegans was developed as a system to study genes required for development and nervous system function. The powerful genetics of C. elegans in combination with molecular and cellular dissections has led to a greater understanding of how p38 and JNK signaling affects many biological processes under normal and stress conditions. This review focuses on the studies revealing context specificity of different stress-activated MAPK components in C. elegans. PMID:26907690

  15. Activation of aryl hydrocarbon receptor signaling by extracts of teak and other wood dusts.

    PubMed

    Wilson, Mark J; Sabbioni, Gabriele; Rando, Roy; Miller, Charles A

    2015-12-01

    Wood dusts, as a group, are categorized as known human carcinogens, but the risks of exposure to specific types of wood dusts and the carcinogenic chemicals they contain are not well studied. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is linked to the carcinogenic action of specific classes of chemicals. Here we examined whether chemicals in various wood dusts had the potential to activate AhR signaling as a potential toxic mechanism of action. We found that methanol extracts of teak, walnut, mahogany, and poplar dusts contained a wide range of AhR ligand activity, whereas extracts of oak, pine, and other softwoods did not contain appreciable activity. Teak dust extract, being particularly potent, was subjected to chemical analysis. The 2-methylanthraquinone (2-MAQ) accounted for the AhR ligand activity and was present at an average concentration of 0.27 parts per hundred in teak dust. Pure 2-MAQ potently induced AhR signaling (EC50 115 nM), confirming that this was the active ligand. Aqueous extracts of teak dust made using yeast or mammalian cell culture medium also contained robust AhR activity, suggesting the 2-MAQ ligand is soluble at bioactive concentrations in physiologically relevant fluids. The high concentration and potency of 2-MAQ in teak wood suggest it may mediate toxic effects through activation of AhR signaling in exposed wood workers.

  16. Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland.

    PubMed

    Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

    2016-04-25

    Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2(+) and Sox9(+) adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors.

  17. Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland

    PubMed Central

    Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

    2016-01-01

    Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2+ and Sox9+ adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors. PMID:27109116

  18. Clicks, whistles and pulses: Passive and active signal use in dolphin communication

    NASA Astrophysics Data System (ADS)

    Herzing, Denise L.

    2014-12-01

    The search for signals out of noise is a problem not only with radio signals from the sky but in the study of animal communication. Dolphins use multiple modalities to communicate including body postures, touch, vision, and most elaborately sound. Like SETI radio signal searches, dolphin sound analysis includes the detection, recognition, analysis, and interpretation of signals. Dolphins use both passive listening and active production to communicate. Dolphins use three main types of acoustic signals: frequency modulated whistles (narrowband with harmonics), echolocation (broadband clicks) and burst pulsed sounds (packets of closely spaced broadband clicks). Dolphin sound analysis has focused on frequency-modulated whistles, yet the most commonly used signals are burst-pulsed sounds which, due to their graded and overlapping nature and bimodal inter-click interval (ICI) rates are hard to categorize. We will look at: 1) the mechanism of sound production and categories of sound types, 2) sound analysis techniques and information content, and 3) examples of lessons learned in the study of dolphin acoustics. The goal of this paper is to provide perspective on how animal communication studies might provide insight to both passive and active SETI in the larger context of searching for life signatures.

  19. Boehmenan, a lignan from Hibiscus ficulneus, showed Wnt signal inhibitory activity.

    PubMed

    Shono, Takumi; Ishikawa, Naoki; Toume, Kazufumi; Arai, Midori A; Ahmed, Firoj; Sadhu, Samir K; Ishibashi, Masami

    2015-07-15

    The Wnt signal pathway modulates numerous biological processes, and its aberrant activation is related to various diseases. Therefore, inhibition of the Wnt signal may provide an effective (or efficient) strategy for these diseases. Cell-based luciferase assay targeting the Wnt signal (TOP assay) revealed that Hibiscus ficulneus extract inhibited the Wnt signal. The activity-guided isolation of the MeOH extract of H. ficulneus stems yielded four known (1-4) lignans along with myriceric acid (5). Compounds 1-4 potently inhibited the Wnt signal with TOPflash IC50 values of 1.0, 4.5, 6.3, and 1.9 μM, respectively. Compound 1 exhibited cytotoxicity against both Wnt-dependent (HCT116) and Wnt-independent (RKO) cells. Western blot analysis showed that 1 decreased the expression of full, cytosolic and nuclear β-catenin along with c-myc in STF/293 cells. Our results suggested that 1 may have inhibited the Wnt signal by decreasing β-catenin levels.

  20. TRIM5 Retroviral Restriction Activity Correlates with the Ability To Induce Innate Immune Signaling

    PubMed Central

    Lascano, Josefina; Uchil, Pradeep D.; Mothes, Walther

    2015-01-01

    ABSTRACT Host restriction factor TRIM5 inhibits retroviral transduction in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. However, the restriction mechanism may not be that simple since TRIM5 E3 ubiquitin ligase activity, the proteasome, autophagy, and TAK1-dependent AP-1 signaling have been suggested to contribute to restriction. Here, we show that, among a panel of seven primate and Carnivora TRIM5 orthologues, each of which has potential for potent retroviral restriction activity, all activated AP-1 signaling. In contrast, TRIM family paralogues most closely related to TRIM5 did not. While each primate species has a single TRIM5 gene, mice have at least seven TRIM5 homologues that cluster into two groups, Trim12a, -b, and -c and Trim30a, -b, -c, and -d. The three Trim12 proteins activated innate immune signaling, while the Trim30 proteins did not, though none of the murine Trim5 homologues restricted any of a panel of cloned retroviruses. To determine if any mouse TRIM5 homologues had potential for restriction activity, each was fused to the human immunodeficiency virus type 1 (HIV-1) CA binding protein cyclophilin A (CypA). The three Trim12-CypA fusions all activated AP-1 and restricted HIV-1 transduction, whereas the Trim30-CypA fusions did neither. AP-1 activation and HIV-1 restriction by the Trim12-CypA fusions were inhibited by disruption of TAK1. Overall then, these experiments demonstrate that there is a strong correlation between TRIM5 retroviral restriction activity and the ability to activate TAK1-dependent innate immune signaling. IMPORTANCE The importance of retroviruses for the evolution of susceptible host organisms cannot be overestimated. Eight percent of the human genome is retrovirus sequence, fixed in the germ line during past infection. Understanding how metazoa protect their genomes from mutagenic retrovirus infection is therefore of fundamental importance to

  1. P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration.

    PubMed

    Hernández-Negrete, Ivette; Carretero-Ortega, Jorge; Rosenfeldt, Hans; Hernández-García, Ricardo; Calderón-Salinas, J Victor; Reyes-Cruz, Guadalupe; Gutkind, J Silvio; Vázquez-Prado, José

    2007-08-10

    Polarized cell migration results from the transduction of extra-cellular cues promoting the activation of Rho GTPases with the intervention of multidomain proteins, including guanine exchange factors. P-Rex1 and P-Rex2 are Rac GEFs connecting Gbetagamma and phosphatidylinositol 3-kinase signaling to Rac activation. Their complex architecture suggests their regulation by protein-protein interactions. Novel mechanisms of activation of Rho GTPases are associated with mammalian target of rapamycin (mTOR), a serine/threonine kinase known as a central regulator of cell growth and proliferation. Recently, two independent multiprotein complexes containing mTOR have been described. mTORC1 links to the classical rapamycin-sensitive pathways relevant for protein synthesis; mTORC2 links to the activation of Rho GTPases and cytoskeletal events via undefined mechanisms. Here we demonstrate that P-Rex1 and P-Rex2 establish, through their tandem DEP domains, interactions with mTOR, suggesting their potential as effectors in the signaling of mTOR to Rac activation and cell migration. This possibility was consistent with the effect of dominant-negative constructs and short hairpin RNA-mediated knockdown of P-Rex1, which decreased mTOR-dependent leucine-induced activation of Rac and cell migration. Rapamycin, a widely used inhibitor of mTOR signaling, did not inhibit Rac activity and cell migration induced by leucine, indicating that P-Rex1, which we found associated to both mTOR complexes, is only active when in the mTORC2 complex. mTORC2 has been described as the catalytic complex that phosphorylates AKT/PKB at Ser-473 and elicits activation of Rho GTPases and cytoskeletal reorganization. Thus, P-Rex1 links mTOR signaling to Rac activation and cell migration.

  2. False Alarm Reduction in BSN-Based Cardiac Monitoring Using Signal Quality and Activity Type Information

    PubMed Central

    Tanantong, Tanatorn; Nantajeewarawat, Ekawit; Thiemjarus, Surapa

    2015-01-01

    False alarms in cardiac monitoring affect the quality of medical care, impacting on both patients and healthcare providers. In continuous cardiac monitoring using wireless Body Sensor Networks (BSNs), the quality of ECG signals can be deteriorated owing to several factors, e.g., noises, low battery power, and network transmission problems, often resulting in high false alarm rates. In addition, body movements occurring from activities of daily living (ADLs) can also create false alarms. This paper presents a two-phase framework for false arrhythmia alarm reduction in continuous cardiac monitoring, using signals from an ECG sensor and a 3D accelerometer. In the first phase, classification models constructed using machine learning algorithms are used for labeling input signals. ECG signals are labeled with heartbeat types and signal quality levels, while 3D acceleration signals are labeled with ADL types. In the second phase, a rule-based expert system is used for combining classification results in order to determine whether arrhythmia alarms should be accepted or suppressed. The proposed framework was validated on datasets acquired using BSNs and the MIT-BIH arrhythmia database. For the BSN dataset, acceleration and ECG signals were collected from 10 young and 10 elderly subjects while they were performing ADLs. The framework reduced the false alarm rate from 9.58% to 1.43% in our experimental study, showing that it can potentially assist physicians in diagnosing a vast amount of data acquired from wireless sensors and enhance the performance of continuous cardiac monitoring. PMID:25671512

  3. Recordings of mucociliary activity in vivo: benefit of fast Fourier transformation of the photoelectric signal.

    PubMed

    Lindberg, S; Cervin, A; Runer, T; Thomasson, L

    1996-09-01

    Investigations of mucociliary activity in vivo are based on photoelectric recordings of light reflections from the mucosa. The alterations in light intensity produced by the beating cilia are picked up by a photodetector and converted to photoelectric signals. The optimal processing of these signals is not known, but in vitro recordings have been reported to benefit from fast Fourier transformation (FFT) of the signal. The aim of the investigation was to study the effect of FFT for frequency analysis of photoelectric signals originating from an artificial light source simulating mucociliary activity or from sinus or nasal mucosa in vivo, as compared to a conventional method of calculating mucociliary wave frequency, in which each peak in the signal is interpreted as a beat (old method). In the experiments with the artificial light source, the FFT system was superior to the conventional method by a factor of 50 in detecting weak signals. By using FFT signal processing, frequency could be correctly calculated in experiments with a compound signal. In experiments in the rabbit maxillary sinus, the spontaneous variations were greater when signals were processed by FFT. The correlation between the two methods was excellent: r = .92. The increase in mucociliary activity in response to the ciliary stimulant methacholine at a dosage of 0.5 microgram/kg was greater measured with the FFT than with the old method (55.3% +/- 8.3% versus 43.0% +/- 8.2%, p < .05, N = 8), and only with the FFT system could a significant effect of a threshold dose (0.05 microgram/kg) of methacholine be detected. In the human nose, recordings from aluminum foil placed on the nasal dorsum and from the nasal septa mucosa displayed some similarities in the lower frequency spectrum (< 5 Hz) attributable to artifacts. The predominant cause of these artifacts was the pulse beat, whereas in the frequency spectrum above 5 Hz, results differed for the two sources of reflected light, the mean frequency in

  4. Rictor/mTORC2 signaling mediates TGFβ1-induced fibroblast activation and kidney fibrosis.

    PubMed

    Li, Jianzhong; Ren, Jiafa; Liu, Xin; Jiang, Lei; He, Weichun; Yuan, Weiping; Yang, Junwei; Dai, Chunsun

    2015-09-01

    The mammalian target of rapamycin (mTOR) was recently identified in two structurally distinct multiprotein complexes: mTORC1 and mTORC2. Previously, we found that Rictor/mTORC2 protects against cisplatin-induced acute kidney injury, but the role and mechanisms for Rictor/mTORC2 in TGFβ1-induced fibroblast activation and kidney fibrosis remains unknown. To study this, we initially treated NRK-49F cells with TGFβ1 and found that TGFβ1 could activate Rictor/mTORC2 signaling in cultured cells. Blocking Rictor/mTORC2 signaling with Rictor or Akt1 small interfering RNAs markedly inhibited TGFβ1-induced fibronection and α-smooth muscle actin expression. Ensuing western blotting or immunostaining results showed that Rictor/mTORC2 signaling was activated in kidney interstitial myofibroblasts from mice with unilateral ureteral obstruction. Next, a mouse model with fibroblast-specific deletion of Rictor was generated. These knockout mice were normal at birth and had no obvious kidney dysfunction or kidney morphological abnormality within 2 months of birth. Compared with control littermates, the kidneys of Rictor knockout mice developed less interstitial extracellular matrix deposition and inflammatory cell infiltration at 1 or 2 weeks after ureteral obstruction. Thus our study suggests that Rictor/mTORC2 signaling activation mediates TGFβ1-induced fibroblast activation and contributes to the development of kidney fibrosis. This may provide a therapeutic target for chronic kidney diseases.

  5. Is bone formation induced by high-frequency mechanical signals modulated by muscle activity?

    PubMed

    Judex, S; Rubin, C T

    2010-03-01

    Bone formation and resorption are sensitive to both external loads arising from gravitational loading as well to internal loads generated by muscular activity. The question as to which of the two sources provides the dominant stimulus for bone homeostasis and new bone accretion is arguably tied to the specific type of activity and anatomical site but it is often assumed that, because of their purportedly greater magnitude, muscle loads modulate changes in bone morphology. High-frequency mechanical signals may provide benefits at low- (<1g) and high- (>1g) acceleration magnitudes. While the mechanisms by which cells perceive high-frequency signals are largely unknown, higher magnitude vibrations can cause large muscle loads and may therefore be sensed by pathways similar to those associated with exercise. Here, we review experimental data to examine whether vibrations applied at very low magnitudes may be sensed directly by transmittance of the signal through the skeleton or whether muscle activity modulates, and perhaps amplifies, the externally applied mechanical stimulus. Current data indicate that the anabolic and anti-catabolic effects of whole body vibrations on the skeleton are unlikely to require muscular activity to become effective. Even high-frequency signals that induce bone matrix deformations of far less than five microstrain can promote bone formation in the absence of muscular activity. This independence of cells on large strains suggests that mechanical interventions can be designed that are both safe and effective.

  6. Cholesterol activates the G-protein coupled receptor Smoothened to promote Hedgehog signaling

    PubMed Central

    Luchetti, Giovanni; Sircar, Ria; Kong, Jennifer H; Nachtergaele, Sigrid; Sagner, Andreas; Byrne, Eamon FX; Covey, Douglas F; Siebold, Christian; Rohatgi, Rajat

    2016-01-01

    Cholesterol is necessary for the function of many G-protein coupled receptors (GPCRs). We find that cholesterol is not just necessary but also sufficient to activate signaling by the Hedgehog (Hh) pathway, a prominent cell-cell communication system in development. Cholesterol influences Hh signaling by directly activating Smoothened (SMO), an orphan GPCR that transmits the Hh signal across the membrane in all animals. Unlike many GPCRs, which are regulated by cholesterol through their heptahelical transmembrane domains, SMO is activated by cholesterol through its extracellular cysteine-rich domain (CRD). Residues shown to mediate cholesterol binding to the CRD in a recent structural analysis also dictate SMO activation, both in response to cholesterol and to native Hh ligands. Our results show that cholesterol can initiate signaling from the cell surface by engaging the extracellular domain of a GPCR and suggest that SMO activity may be regulated by local changes in cholesterol abundance or accessibility. DOI: http://dx.doi.org/10.7554/eLife.20304.001 PMID:27705744

  7. Effects of anesthesia on BOLD signal and neuronal activity in the somatosensory cortex

    PubMed Central

    Aksenov, Daniil P; Li, Limin; Miller, Michael J; Iordanescu, Gheorghe; Wyrwicz, Alice M

    2015-01-01

    Most functional magnetic resonance imaging (fMRI) animal studies rely on anesthesia, which can induce a variety of drug-dependent physiological changes, including depression of neuronal activity and cerebral metabolism as well as direct effects on the vasculature. The goal of this study was to characterize the effects of anesthesia on the BOLD signal and neuronal activity. Simultaneous fMRI and electrophysiology were used to measure changes in single units (SU), multi-unit activity (MUA), local field potentials (LFP), and the blood oxygenation level-dependent (BOLD) response in the somatosensory cortex during whisker stimulation of rabbits before, during and after anesthesia with fentanyl or isoflurane. Our results indicate that anesthesia modulates the BOLD signal as well as both baseline and stimulus-evoked neuronal activity, and, most significantly, that the relationship between the BOLD and electrophysiological signals depends on the type of anesthetic. Specifically, the behavior of LFP observed under isoflurane did not parallel the behavior of BOLD, SU, or MUA. These findings suggest that the relationship between these signals may not be straightforward. BOLD may scale more closely with the best measure of the excitatory subcomponents of the underlying neuronal activity, which may vary according to experimental conditions that alter the excitatory/inhibitory balance in the cortex. PMID:26104288

  8. Immune signaling pathways activated in response to different pathogenic micro-organisms in Bombyx mori.

    PubMed

    Liu, Wei; Liu, Jiabin; Lu, Yahong; Gong, Yongchang; Zhu, Min; Chen, Fei; Liang, Zi; Zhu, Liyuan; Kuang, Sulan; Hu, Xiaolong; Cao, Guangli; Xue, Renyu; Gong, Chengliang

    2015-06-01

    The JAK/STAT, Toll, Imd, and RNAi pathways are the major signaling pathways associated with insect innate immunity. To explore the different immune signaling pathways triggered in response to pathogenic micro-organism infections in the silkworm, Bombyx mori, the expression levels of the signal transducer and activator of transcription (BmSTAT), spatzle-1 (Bmspz-1), peptidoglycan-recognition protein LB (BmPGRP-LB), peptidoglycan-recognition protein LE (BmPGRP-LE), argonaute 2 (Bmago2), and dicer-2 (Bmdcr2) genes after challenge with Escherichia coli (E. coli), Serratiamarcescens (Sm), Bacillus bombyseptieus (Bab), Beauveriabassiana (Beb), nucleopolyhedrovirus (BmNPV), cypovirus (BmCPV), bidensovirus (BmBDV), or Nosemabombycis (Nb) were determined using real-time PCR. We found that the JAK/STAT pathway could be activated by challenge with BmNPV and BmBDV, the Toll pathway could be most robustly induced by challenge with Beb, the Imd pathway was mainly activated in response to infection by E. coli and Sm, and the RNAi pathway was not activated by viral infection, but could be triggered by some bacterial infections. These findings yield insights into the immune signaling pathways activated in response to different pathogenic micro-organisms in the silkworm.

  9. Bz-423 superoxide signals apoptosis via selective activation of JNK, Bak, and Bax.

    PubMed

    Blatt, Neal B; Boitano, Anthony E; Lyssiotis, Costas A; Opipari, Anthony W; Glick, Gary D

    2008-11-01

    Bz-423 is a proapoptotic 1,4-benzodiazepine with potent therapeutic properties in murine models of lupus and psoriasis. Bz-423 modulates the F(1)F(0)-ATPase, inducing the formation of superoxide within the mitochondrial respiratory chain, which then functions as a second messenger initiating apoptosis. Herein, we report the signaling pathway activated by Bz-423 in mouse embryonic fibroblasts containing knockouts of key apoptotic proteins. Bz-423-induced superoxide activates cytosolic ASK1 and its release from thioredoxin. A mitogen-activated protein kinase cascade follows, leading to the specific phosphorylation of JNK. JNK signals activation of Bax and Bak which then induces mitochondrial outer membrane permeabilization to cause the release of cytochrome c and a commitment to apoptosis. The response of these cells to Bz-423 is critically dependent on both superoxide and JNK activation as antioxidants and the JNK inhibitor SP600125 prevents Bax translocation, cytochrome c release, and cell death. These results demonstrate that superoxide generated from the mitochondrial respiratory chain as a consequence of a respiratory transition can signal a sequential and specific apoptotic response. Collectively, these data suggest that the selectivity of Bz-423 observed in vivo results from cell-type specific differences in redox balance and signaling by ASK1 and Bcl-2 proteins.

  10. Surfactant Protein A integrates activation signal strength to differentially modulate T cell proliferation

    PubMed Central

    Mukherjee, Sambuddho; Giamberardino, Charles; Thomas, Joseph; Evans, Kathy; Goto, Hisatsugu; Ledford, Julie G; Hsia, Bethany; Pastva, Amy M; Wright, Jo Rae

    2011-01-01

    Pulmonary surfactant lipoproteins lower the surface tension at the alveolar:airway interface of the lung and participate in host defense. Previous studies reported that surfactant protein A (SP-A) inhibits lymphocyte proliferation. We hypothesized that SP-A mediated modulation of T cell activation depends upon the strength, duration and type of lymphocyte activating signals. Modulation of T cell signal strength imparted by different activating agents ex and in vivo in different mouse models, and in vitro with human T cells show a strong correlation between strength of signal (SoS) and functional effects of SP-A interactions. T cell proliferation is enhanced in the presence of SP-A at low SoS imparted by exogenous mitogens, specific antibodies, APCs or in homeostatic proliferation. Proliferation is inhibited at higher SoS imparted by different doses of the same T cell mitogens, or indirect stimuli such as LPS. Importantly, reconstitution with exogenous SP-A into the lungs of SP-A-/- mice stimulated with a strong signal also resulted in suppression of T cell proliferation, while elevating baseline proliferation in unstimulated T cells. These signal strength and SP-A dependent effects are mediated by changes in intracellular Ca2+ levels over time, involving extrinsic Ca2+ activated channels late during activation. These effects are intrinsic to the global T cell population, and are manifested in vivo in naïve as well as memory phenotype T cells. Thus, SP-A appears to integrate signal thresholds to control T cell proliferation. PMID:22219327

  11. Sucralose activates an ERK1/2-ribosomal protein S6 signaling axis.

    PubMed

    Guerra, Marcy L; Kalwat, Michael A; McGlynn, Kathleen; Cobb, Melanie H

    2017-02-01

    The sweetener sucralose can signal through its GPCR receptor to induce insulin secretion from pancreatic β cells, but the downstream signaling pathways involved are not well-understood. Here we measure responses to sucralose, glucagon-like peptide 1, and amino acids in MIN6 β cells. Our data suggest a signaling axis, whereby sucralose induces calcium and cAMP, activation of ERK1/2, and site-specific phosphorylation of ribosomal protein S6. Interestingly, sucralose acted independently of mTORC1 or ribosomal S6 kinase (RSK). These results suggest that sweeteners like sucralose can influence β-cell responses to secretagogues like glucose through metabolic as well as GPCR-mediated pathways. Future investigation of novel sweet taste receptor signaling pathways in β cells will have implications for diabetes and other emergent fields involving these receptors.

  12. Cell-autonomous activation of Hedgehog signaling inhibits brown adipose tissue development.

    PubMed

    Nosavanh, LaGina; Yu, Da-Hai; Jaehnig, Eric J; Tong, Qiang; Shen, Lanlan; Chen, Miao-Hsueh

    2015-04-21

    Although recent studies have shown that brown adipose tissue (BAT) arises from progenitor cells that also give rise to skeletal muscle, the developmental signals that control the formation of BAT remain largely unknown. Here, we show that brown preadipocytes possess primary cilia and can respond to Hedgehog (Hh) signaling. Furthermore, cell-autonomous activation of Hh signaling blocks early brown-preadipocyte differentiation, inhibits BAT formation in vivo, and results in replacement of neck BAT with poorly differentiated skeletal muscle. Finally, we show that Hh signaling inhibits BAT formation partially through up-regulation of chicken ovalbumin upstream promoter transcription factor II (COUP-TFII). Taken together, our studies uncover a previously unidentified role for Hh as an inhibitor of BAT development.

  13. Low-cost detection of RC-IED activation signals in VHF band

    NASA Astrophysics Data System (ADS)

    Camargo Suarez, Victor Hugo; Marulanda B., Jose Ignacio

    2014-05-01

    The proliferation of Radio Controlled Improvised Explosive Devices (RC-IED) is a growing threat around the world. The ease of construction and low cost of these devices are transforming common things in lethal tramps. The fight against this threats normally involves the use of sophisticated and expensive equipment of Electronic Warfare based on high speed DSP systems, just to detect the presence of detonation signals. In this work is showed how to find activation signals based on the characteristic of the power in a specific band and the previous knowledge about the detonation signals. As proof of concept we have taken the information about the RC-IEDs used in the Colombian conflict and develop an algorithm to find detonation signals based on the measured power in frequencies between 136 MHz and 174 MHz (2 meter civil band)

  14. Cross Psi(B)-energy operator-based signal detection.

    PubMed

    Boudraa, Abdel-Ouahab; Cexus, Jean-Christophe; Abed-Meraim, Karim

    2008-06-01

    In this paper, two methods for signal detection and time-delay estimation based on the cross Psi(B)-energy operator are proposed. These methods are well suited for mono-component AM-FM signals. The Psi(B) energy operator measures how much one signal is present in another one. The peak of the Psi(B) operator corresponds to the maximum of interaction between the two signals. Compared to the cross-correlation function, the Psi(B) operator includes temporal information and relative changes of the signal which are reflected in its first and second derivatives. The discrete version of the continuous-time form of the Psi(B) operator, which is used in its implementation, is presented. The methods are illustrated on synthetic and real signals and the results compared to those of the matched filter and the cross correlation. The real signals correspond to impulse responses of buried objects obtained by active sonar in iso-speed single path environments.

  15. A Phosphatase Activity of Sts-1 Contributes to the Suppression of TCR Signaling

    SciTech Connect

    Mikhailik,A.; Ford, B.; Keller, J.; Chen, Y.; Nassar, N.; Carpino, N.

    2007-01-01

    Precise signaling by the T cell receptor (TCR) is crucial for a proper immune response. To ensure that T cells respond appropriately to antigenic stimuli, TCR signaling pathways are subject to multiple levels of regulation. Sts-1 negatively regulates signaling pathways downstream of the TCR by an unknown mechanism(s). Here, we demonstrate that Sts-1 is a phosphatase that can target the tyrosine kinase Zap-70 among other proteins. The X-ray structure of the Sts-1 C terminus reveals that it has homology to members of the phosphoglycerate mutase/acid phosphatase (PGM/AcP) family of enzymes, with residues known to be important for PGM/AcP catalytic activity conserved in nature and position in Sts-1. Point mutations that impair Sts-1 phosphatase activity in vitro also impair the ability of Sts-1 to regulate TCR signaling in T cells. These observations reveal a PGM/AcP-like enzyme activity involved in the control of antigen receptor signaling.

  16. Prostaglandin F2α regulates the expression of uterine activation proteins via multiple signalling pathways.

    PubMed

    Xu, Chen; You, Xingji; Liu, Weina; Sun, Qianqian; Ding, Xiaoying; Huang, Ying; Ni, Xin

    2015-01-01

    Prostaglandin F2α (PGF2A) has multiple roles in the birth process in addition to its vital contractile role. Our previous study has demonstrated that PGF2A can modulate uterine activation proteins (UAPs) in cultured pregnant human myometrial smooth muscle cells (HMSMCs). The objective of this study was to define the signalling pathways responsible for PGF2A modulation of UAPs in myometrium. It was found that PGF2A stimulated the expression of (GJA1) connexin 43 (CX43), prostaglandin endoperoxide synthase 2 (PTGS2) and oxytocin receptor (OTR) in cultured HMSMCs. The inhibitors of phospholipase C (PLC) and protein kinase C (PKC) blocked PGF2A-stimulated expression of CX43. The inhibitors of ERK, P38 and NFκB also blocked the effect of PGF2A on CX43 expression, whereas PI3K and calcineurin/nuclear factor of activated T-cells (NFAT) pathway inhibitors did not reverse the effect of PGF2A on CX43. For PTGS2 and OTR, PLC, PI3K, P38 and calcineurin/NFAT signalling pathways were involved in PGF2A action, whereas PKC and NFκB signalling were not involved. In addition, PGF2A activated NFAT, PI3K, NFκB, ERK and P38 signalling pathways. Our data suggest that PGF2A stimulates CX43, PTGS2 and OTR through divergent signalling pathways.

  17. Graded boosting of synaptic signals by low-threshold voltage-activated calcium conductance

    PubMed Central

    Carbó Tano, Martín; Vilarchao, María Eugenia

    2015-01-01

    Low-threshold voltage-activated calcium conductances (LT-VACCs) play a substantial role in shaping the electrophysiological attributes of neurites. We have investigated how these conductances affect synaptic integration in a premotor nonspiking (NS) neuron of the leech nervous system. These cells exhibit an extensive neuritic tree, do not fire Na+-dependent spikes, but express an LT-VACC that was sensitive to 250 μM Ni2+ and 100 μM NNC 55-0396 (NNC). NS neurons responded to excitation of mechanosensory pressure neurons with depolarizing responses for which amplitude was a linear function of the presynaptic firing frequency. NNC decreased these synaptic responses and abolished the concomitant widespread Ca2+ signals. Coherent with the interpretation that the LT-VACC amplified signals at the postsynaptic level, this conductance also amplified the responses of NS neurons to direct injection of sinusoidal current. Synaptic amplification thus is achieved via a positive feedback in which depolarizing signals activate an LT-VACC that, in turn, boosts these signals. The wide distribution of LT-VACC could support the active propagation of depolarizing signals, turning the complex NS neuritic tree into a relatively compact electrical compartment. PMID:25972583

  18. Epithelial membrane protein 3 regulates TGF-β signaling activation in CD44-high glioblastoma.

    PubMed

    Jun, Fu; Hong, Jidong; Liu, Qin; Guo, Yong; Liao, Yiwei; Huang, Jianghai; Wen, Sailan; Shen, Liangfang

    2016-08-05

    Although epithelial membrane protein 3 (EMP3) has been implicated as a candidate tumor suppressor gene for low grade glioma, its biological function in glioblastoma multiforme (GBM) still remains poorly understood. Herein, we showed that EMP3 was highly expressed in CD44-high primary GBMs. Depletion of EMP3 expression suppressed cell proliferation, impaired in vitro tumorigenic potential and induced apoptosis in CD44-high GBM cell lines. We also identified TGF-β/Smad2/3 signaling pathway as a potential target of EMP3. EMP3 interacts with TGF-β receptor type 2 (TGFBR2) upon TGF-β stimulation in GBM cells. Consequently, the EMP3-TGFBR2 interaction regulates TGF-β/Smad2/3 signaling activation and positively impacts on TGF-β-stimulated gene expression and cell proliferation in vitro and in vivo. Highly correlated protein expression of EMP3 and TGF-β/Smad2/3 signaling pathway components was also observed in GBM specimens, confirming the clinical relevancy of activated EMP3/TGF-β/Smad2/3 signaling in GBM. In conclusion, our findings revealed that EMP3 might be a potential target for CD44-high GBMs and highlight the essential functions of EMP3 in TGF-β/Smad2/3 signaling activation and tumor progression.

  19. A phosphatase activity of Sts-1 contributes to the suppression TCR signaling

    PubMed Central

    Mikhailik, Anatoly; Ford, Bradley; Keller, James; Chen, Yunting; Nassar, Nicolas; Carpino, Nick

    2009-01-01

    Summary Precise signaling by the T cell receptor (TCR) is crucial for a proper immune response. To ensure that T cells respond appropriately to antigenic stimuli, TCR signaling pathways are subject to multiple levels of regulation. Sts-1 negatively regulates signaling pathways downstream of the TCR by an unknown mechanism(s). Here, we demonstrate that Sts-1 is a phosphatase that can target the tyrosine kinase Zap-70 among other proteins. The x-ray structure of the Sts-1 C-terminus reveals that it has homology to members of the phosphoglycerate mutase/acid phosphatase (PGM/AcP) family of enzymes, with residues known to be important for PGM/AcP catalytic activity conserved in nature and position in Sts-1. Point mutations that impair Sts-1 phosphatase activity in vitro also impair the ability of Sts-1 to regulate TCR signaling in T cells. These observations reveal a PGM/AcP-like enzyme activity involved in the control of antigen receptor signaling. PMID:17679096

  20. Mechanical Stretch-Induced Activation of ROS/RNS Signaling in Striated Muscle

    PubMed Central

    Ward, Christopher W.; Prosser, Benjamin L.

    2014-01-01

    Significance: Mechanical activation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) occurs in striated muscle and affects Ca2+ signaling and contractile function. ROS/RNS signaling is tightly controlled, spatially compartmentalized, and source specific. Recent Advances: Here, we review the evidence that within the contracting myocyte, the trans-membrane protein NADPH oxidase 2 (Nox2) is the primary source of ROS generated during contraction. We also review a newly characterized signaling cascade in cardiac and skeletal muscle in which the microtubule network acts as a mechanotransduction element that activates Nox2-dependent ROS generation during mechanical stretch, a pathway termed X-ROS signaling. Critical Issues: In the heart, X-ROS acts locally and affects the sarcoplasmic reticulum (SR) Ca2+ release channels (ryanodine receptors) and tunes Ca2+ signaling during physiological behavior, but excessive X-ROS can promote Ca2+-dependent arrhythmias in pathology. In skeletal muscle, X-ROS sensitizes Ca2+-permeable sarcolemmal “transient receptor potential” channels, a pathway that is critical for sustaining SR load during repetitive contractions, but when in excess, it is maladaptive in diseases such as Duchenne Musclar dystrophy. Future Directions: New advances in ROS/RNS detection as well as molecular manipulation of signaling pathways will provide critical new mechanistic insights into the details of X-ROS signaling. These efforts will undoubtedly reveal new avenues for therapeutic intervention in the numerous diseases of striated muscle in which altered mechanoactivation of ROS/RNS production has been identified. Antioxid. Redox Signal. 20, 929–936. PMID:23971496

  1. 50 CFR 216.270 - Specified activity and specified geographical region.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... the activities described in paragraph (c) of this section. (b) The taking of marine mammals by the.... lat.; 127°10′04″ W. long. and 24°00′01″ N. lat.; 125°00′03″ W. long. (c) The taking of marine mammals... the following mid-frequency active sonar (MFAS) and high frequency active sonar (HFAS) sources,...

  2. 50 CFR 216.270 - Specified activity and specified geographical region.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... the activities described in paragraph (c) of this section. (b) The taking of marine mammals by the.... lat.; 127°10′04″ W. long. and 24°00′01″ N. lat.; 125°00′03″ W. long. (c) The taking of marine mammals... the following mid-frequency active sonar (MFAS) and high frequency active sonar (HFAS) sources,...

  3. Binaural sonar electronic travel aid provides vibrotactile cues for landmark, reflector motion and surface texture classification.

    PubMed

    Kuc, Roman

    2002-10-01

    Electronic travel aids (ETAs) for the blind commonly employ conventional time-of-flight sonars to provide range measurements, but their wide beams prevent accurate determination of object bearing. We describe a binaural sonar that detects objects over a wider bearing interval compared with a single transducer and also determines if the object lies to the left or right of the sonar axis in a robust manner. The sonar employs a pair of Polaroid 6500 ranging modules connected to Polaroid 7000 transducers operating simultaneously in a binaural array configuration. The sonar determines which transducer detects the echo first. An outward vergence angle between the transducers improves the first-echo detection reliability by increasing the delay between the two detected echoes, a consequence of threshold detection. We exploit this left/right detection capability in an ETA that provides vibrotactile feedback. Pager motors mount on both sides of the sonar, possibly worn on the user's wrists. The motor on the same side as the reflecting object vibrates with speed inversely related to range. As the sonar or object moves, vibration patterns provide landmark, motion and texture cues. Orienting the sonar at 45 degrees relative to the travel direction and passing a right-angle corner produces a characteristic vibrational pattern. When pointing the sonar at a moving object, such as a fluttering flag, the motors alternate in a manner to give the user a perception of the object motion. When the sonar translates or rotates to scan a foliage surface, the vibrational patterns are related to the surface scatterer distribution, allowing the user to identify the foliage.

  4. Optimized passive sonar placement to allow improved interdiction

    NASA Astrophysics Data System (ADS)

    Johnson, Bruce A.; Matthews, Cameron

    2016-05-01

    footprint. The resulting coverage optimizes the likelihood of encounter given an arbitrary sensor profile and threat from a free field statistical model approach. The free field statistical model is particularly applicable to worst case scenario modeling in open ocean operational profiles where targets to do not follow a particular pattern in any of the modeled dimensions. We present an algorithmic testbed which shows how to achieve approximately optimal solutions to the AGP for a network of underwater sensor nodes with or without effector systems for engagement while operating under changing environmental circumstances. The means by which we accomplish this goal are three-fold: 1) Develop a 3D model for the sonar signal propagating through the underwater environment 2) Add rigorous physics-based modeling of environmental events which can affect sensor information acquisition 3) Provide innovative solutions to the AGP which account for the environmental circumstances affecting sensor performance.

  5. Activation of the wnt/β-Catenin Signaling Pathway in Polymyositis, Dermatomyositis and Duchenne Muscular Dystrophy

    PubMed Central

    Liu, Fuchen; Liang, Zonglai; Xu, Jingwen; Li, Wei; Zhao, Dandan; Zhao, Yuying

    2016-01-01

    Background and Purpose The wnt/β-catenin signaling pathway plays a critical role in embryonic development and adult-tissue homeostasis. Recent investigations implicate the importance of wnt/β-catenin signaling in normal wound healing and its sustained activation being associated with fibrogenesis. We investigated the immunolocalization and activation of wnt/β-catenin in polymyositis (PM), dermatomyositis (DM), and Duchenne muscular dystrophy (DMD). Methods Immunofluorescence staining and Western blot analysis of β-catenin were performed in muscle specimens from 6 PM, 8 DM, and 6 DMD subjects. The β-catenin/Tcf4 DNA-binding activity in muscle was studied using an electrophoretic mobility shift assay (EMSA), and serum wnt/β-catenin/Tcf transcriptional activity was measured using a luciferase reporter gene assay. Results Immunoreactivity for β-catenin was found in the cytoplasm and nuclei of muscle fibers in PM, DM, and DMD. The protein level of β-catenin was elevated, and EMSA analysis confirmed the activation of wnt/β-catenin signaling. The transcriptional activities of β-catenin/Tcf in the circulation were increased in patients with PM, DM, and DMD, especially in those with interstitial lung disease, and these transcriptional activities decreased when PM or DM patients exhibited obvious clinical improvements. Conclusions Our findings indicate that wnt/β-catenin signaling is activated in PM, DM, and DMD. Its activation in muscle tissue and the circulation may play a role in modulating muscle regeneration and be at least partly involved in the process of muscle and pulmonary fibrosis. PMID:27165423

  6. Discrete Dynamics Model for the Speract-Activated Ca2+ Signaling Network Relevant to Sperm Motility

    PubMed Central

    Espinal, Jesús; Aldana, Maximino; Guerrero, Adán; Wood, Christopher

    2011-01-01

    Understanding how spermatozoa approach the egg is a central biological issue. Recently a considerable amount of experimental evidence has accumulated on the relation between oscillations in intracellular calcium ion concentration ([Ca]) in the sea urchin sperm flagellum, triggered by peptides secreted from the egg, and sperm motility. Determination of the structure and dynamics of the signaling pathway leading to these oscillations is a fundamental problem. However, a biochemically based formulation for the comprehension of the molecular mechanisms operating in the axoneme as a response to external stimulus is still lacking. Based on experiments on the S. purpuratus sea urchin spermatozoa, we propose a signaling network model where nodes are discrete variables corresponding to the pathway elements and the signal transmission takes place at discrete time intervals according to logical rules. The validity of this model is corroborated by reproducing previous empirically determined signaling features. Prompted by the model predictions we performed experiments which identified novel characteristics of the signaling pathway. We uncovered the role of a high voltage-activated channel as a regulator of the delay in the onset of fluctuations after activation of the signaling cascade. This delay time has recently been shown to be an important regulatory factor for sea urchin sperm reorientation. Another finding is the participation of a voltage-dependent calcium-activated channel in the determination of the period of the fluctuations. Furthermore, by analyzing the spread of network perturbations we find that it operates in a dynamically critical regime. Our work demonstrates that a coarse-grained approach to the dynamics of the signaling pathway is capable of revealing regulatory sperm navigation elements and provides insight, in terms of criticality, on the concurrence of the high robustness and adaptability that the reproduction processes are predicted to have developed

  7. Phosphatidylserine enhances IKBKAP transcription by activating the MAPK/ERK signaling pathway.

    PubMed

    Donyo, Maya; Hollander, Dror; Abramovitch, Ziv; Naftelberg, Shiran; Ast, Gil

    2016-04-01

    Familial dysautonomia (FD) is a genetic disorder manifested due to abnormal development and progressive degeneration of the sensory and autonomic nervous system. FD is caused by a point mutation in the IKBKAP gene encoding the IKAP protein, resulting in decreased protein levels. A promising potential treatment for FD is phosphatidylserine (PS); however, the manner by which PS elevates IKAP levels has yet to be identified. Analysis of ChIP-seq results of the IKBKAP promoter region revealed binding of the transcription factors CREB and ELK1, which are regulated by the mitogen-activated protein kinase (MAPK)/extracellular-regulated kinase (ERK) signaling pathway. We show that PS treatment enhanced ERK phosphorylation in cells derived from FD patients. ERK activation resulted in elevated IKBKAP transcription and IKAP protein levels, whereas pretreatment with the MAPK inhibitor U0126 blocked elevation of the IKAP protein level. Overexpression of either ELK1 or CREB activated the IKBKAP promoter, whereas downregulation of these transcription factors resulted in a decrease of the IKAP protein. Additionally, we show that PS improves cell migration, known to be enhanced by MAPK/ERK activation and abrogated in FD cells. In conclusion, our results demonstrate that PS activates the MAPK/ERK signaling pathway, resulting in activation of transcription factors that bind the promoter region of IKBKAP and thus enhancing its transcription. Therefore, compounds that activate the MAPK/ERK signaling pathway could constitute potential treatments for FD.

  8. Activation of Notch1 signaling in cardiogenic mesoderm induces abnormal heart morphogenesis in mouse.

    PubMed

    Watanabe, Yusuke; Kokubo, Hiroki; Miyagawa-Tomita, Sachiko; Endo, Maho; Igarashi, Katsuhide; Aisaki, Ken ichi; Kanno, Jun; Saga, Yumiko

    2006-05-01

    Notch signaling is implicated in many developmental processes. In our current study, we have employed a transgenic strategy to investigate the role of Notch signaling during cardiac development in the mouse. Cre recombinase-mediated Notch1 (NICD1) activation in the mesodermal cell lineage leads to abnormal heart morphogenesis, which is characterized by deformities of the ventricles and atrioventricular (AV) canal. The major defects observed include impaired ventricular myocardial differentiation, the ectopic appearance of cell masses in the AV cushion, the right-shifted interventricular septum (IVS) and impaired myocardium of the AV canal. However, the fates of the endocardium and myocardium were not disrupted in NICD1-activated hearts. One of the Notch target genes, Hesr1, was found to be strongly induced in both the ventricle and the AV canal of NICD1-activated hearts. However, a knockout of the Hesr1 gene from NICD-activated hearts rescues only the abnormality of the AV myocardium. We searched for additional possible targets of NICD1 activation by GeneChip analysis and found that Wnt2, Bmp6, jagged 1 and Tnni2 are strongly upregulated in NICD1-activated hearts, and that the activation of these genes was also observed in the absence of Hesr1. Our present study thus indicates that the Notch1 signaling pathway plays a suppressive role both in AV myocardial differentiation and the maturation of the ventricular myocardium.

  9. Characteristics of a sandy depositional lobe on the outer Mississippi fan from SeaMARC IA sidescan sonar images

    SciTech Connect

    Twichell, D.C.; Schwab, W.C. ); Nelson, C.H.; Lee, H.J. ); Kenyon, N.H. )

    1992-08-01

    SeaMARC IA sidescan sonar images of the distal reaches of a depositional lobe on the Mississippi Fan show that channelized rather than unconfined transport was the dominant transport mechanism for coarse-grained sediment during the formation of this part of the deep-sea fan. Overbank sheet flow of sands was not an important process in the transport and deposition of the sandy and silty sediment found on this fan. The dendritic distributary pattern and the high order of splaying of the channels, only one which appears to have been active at a time, suggest that coarse-grained deposits on this fan are laterally discontinuous.

  10. GABA and neuroligin signaling: linking synaptic activity and adhesion in inhibitory synapse development

    PubMed Central

    Huang, Z. Josh; Scheiffele, Peter

    2013-01-01

    GABA-mediated synaptic inhibition is crucial in neural circuit operations. In mammalian brains, the development of inhibitory synapses and innervation patterns is often a prolonged postnatal process, regulated by neural activity. Emerging evidence indicates that GABA acts beyond inhibitory transmission and regulates inhibitory synapse development. Indeed, GABAA receptors not only function as chloride channels that regulate membrane voltage and conductance but also play structural roles in synapse maturation and stabilization. The link from GABAA receptors to post- and pre- synaptic adhesion is likely mediated, in part, by neuroligin-reurexin interactions, which are potent in promoting GABAergic synapse formation. Therefore, similar to glutamate signaling at excitatory synapse, GABA signaling may coordinate maturation of pre- and post- synaptic sites at inhibitory synapses. Defining the many steps from GABA signaling to receptor trafficking/stability and neuroligin function will provide further mechanistic insights into activity-dependent development and possibly plasticity of inhibitory synapses. PMID:18513949

  11. Activation of Wnt Signaling by Chemically Induced Dimerization of LRP5 Disrupts Cellular Homeostasis

    PubMed Central

    Pond, Adam C.; Seethammagari, Mamatha; Chiou, Shin-Heng; Cho, Kyucheol; Carstens, Julienne L.; Decker, William K.; McCrea, Pierre D.; Ittmann, Michael M.; Rosen, Jeffrey M.; Spencer, David M.

    2012-01-01

    Wnt signaling is crucial for a variety of biological processes, including body axis formation, planar polarity, stem cell maintenance and cellular differentiation. Therefore, targeted manipulation of Wnt signaling in vivo would be extremely useful. By applying chemical inducer of dimerization (CID) technology, we were able to modify the Wnt co-receptor, low-density lipoprotein (LDL)-receptor-related protein 5 (LRP5), to generate the synthetic ligand inducible Wnt switch, iLRP5. We show that iLRP5 oligomerization results in its localization to disheveled-containing punctate structures and sequestration of scaffold protein Axin, leading to robust β-catenin-mediated signaling. Moreover, we identify a novel LRP5 cytoplasmic domain critical for its intracellular localization and casein kinase 1-dependent β-catenin signaling. Finally, by utilizing iLRP5 as a Wnt signaling switch, we generated the Ubiquitous Activator of β-catenin (Ubi-Cat) transgenic mouse line. The Ubi-Cat line allows for nearly ubiquitous expression of iLRP5 under control of the H-2Kb promoter. Activation of iLRP5 in isolated prostate basal epithelial stem cells resulted in expansion of p63+ cells and development of hyperplasia in reconstituted murine prostate grafts. Independently, iLRP5 induction in adult prostate stroma enhanced prostate tissue regeneration. Moreover, induction of iLRP5 in male Ubi-Cat mice resulted in prostate tumor progression over several months from prostate hyperplasia to adenocarcinoma. We also investigated iLRP5 activation in Ubi-Cat-derived mammary cells, observing that prolonged activation results in mammary tumor formation. Thus, in two distinct experimental mouse models, activation of iLRP5 results in disruption of tissue homeostasis, demonstrating the utility of iLRP5 as a novel research tool for determining the outcome of Wnt activation in a precise spatially and temporally determined fashion. PMID:22303459

  12. Signal integration by Ca(2+) regulates intestinal stem-cell activity.

    PubMed

    Deng, Hansong; Gerencser, Akos A; Jasper, Heinrich

    2015-12-10

    Somatic stem cells maintain tissue homeostasis by dynamically adjusting proliferation and differentiation in response to stress and metabolic cues. Here we identify Ca(2+) signalling as a central regulator of intestinal stem cell (ISC) activity in Drosophila. We show that dietary L-glutamate stimulates ISC division and gut growth. The metabotropic glutamate receptor (mGluR) is required in ISCs for this response, and for an associated modulation of cytosolic Ca(2+) oscillations that results in sustained high cytosolic Ca(2+) concentrations. High cytosolic Ca(2+) concentrations induce ISC proliferation by regulating Calcineurin and CREB-regulated transcriptional co-activator (Crtc). In response to a wide range of dietary and stress stimuli, ISCs reversibly transition between Ca(2+) oscillation states that represent poised or activated modes of proliferation, respectively. We propose that the dynamic regulation of intracellular Ca(2+) levels allows effective integration of diverse mitogenic signals in ISCs to adapt their proliferative activity to the needs of the tissue.

  13. Activity-dependent signaling: influence on plasticity in circuits controlling fear-related behavior

    PubMed Central

    Hill, Julia L; Martinowich, Keri

    2015-01-01

    Fear regulation is impaired in anxiety and trauma-related disorders. Patients experience heightened fear expression and reduced ability to extinguish fear memories. Because fear regulation is abnormal in these disorders and extinction recapitulates current treatment strategies, understanding the underlying mechanisms is vital for developing new treatments. This is critical because although extinction-based exposure therapy is a mainstay of treatment, relapse is common. We examine recent findings describing changes in network activity and functional connectivity within limbic circuits during fear regulation, and explore how activity-dependent signaling contributes to the neural activity patterns that control fear and anxiety. We review the role of the prototypical activity-dependent molecule, brain-derived neurotrophic factor (BDNF), whose signaling has been critically linked to regulation of fear behavior. PMID:26485574

  14. Bridging the gap between GPCR activation and behaviour: oxytocin and prolactin signalling in the hypothalamus.

    PubMed

    van den Burg, Erwin H; Neumann, Inga D

    2011-02-01

    Neuropeptides of the brain are important neuromodulators, controlling behaviour and physiology. They signal through G protein-coupled receptors (GPCR) that couple to complex intracellular signalling pathways. These signalling networks integrate information from multiple sources, resulting in appropriate physiological and behavioural responses to environmental and internal cues. This paper will focus on the neuropeptides oxytocin and prolactin with respect to (1) the regulation of neuroendocrine stress responses and anxiety, and (2) the receptor-mediated molecular mechanisms underlying these actions of the neuropeptides. Besides its significant reproductive functions when released into the bloodstream, brain oxytocin reduces the activity of the hypothalamo-pituitary-adrenal (HPA) axis as well as anxiety-related behaviour in male and female rats. Oxytocin mediates its anxiolytic effect, at least in part, via binding to its GPCR in the hypothalamic paraventricular nucleus, followed by transactivation of the epidermal growth factor receptor, and subsequent activation of a MEK-extracellular signal-regulated kinase (ERK) MAP kinase pathway. Prolactin, by binding to its GPCR receptors, of which there are short and long forms, also activates ERK, and this is necessary for the control of the expression of corticotrophin-releasing hormone-an important regulator of the HPA axis. Liganded oxytocin and prolactin may also recruit other signalling pathways, but how these pathways contribute to the observed behavioural and physiological effects remains to be established. GPCR-mediated oxytocin and prolactin neuronal signalling are illustrative of the complexity of GPCR-activated regulation of appropriate neuroendocrine and behavioural responses to environmental and physiological demands.

  15. Activation of Wnt Signaling in Cortical Neurons Enhances Glucose Utilization through Glycolysis.

    PubMed

    Cisternas, Pedro; Salazar, Paulina; Silva-Álvarez, Carmen; Barros, L Felipe; Inestrosa, Nibaldo C

    2016-12-09

    The Wnt signaling pathway is critical for a number of functions in the central nervous system, including regulation of the synaptic cleft structure and neuroprotection against injury. Deregulation of Wnt signaling has been associated with several brain pathologies, including Alzheimer's disease. In recent years, it has been suggested that the Wnt pathway might act as a central integrator of metabolic signals from peripheral organs to the brain, which would represent a new role for Wnt signaling in cell metabolism. Energy metabolism is critical for normal neuronal function, which mainly depends on glucose utilization. Brain energy metabolism is important in almost all neurological disorders, to which a decrease in the capacity of the brain to utilize glucose has been linked. However, little is known about the relationship between Wnt signaling and neuronal glucose metabolism in the cellular context. In the present study, we found that acute treatment with the Wnt3a ligand induced a large increase in glucose uptake, without changes in the expression or localization of glucose transporter type 3. In addition, we observed that Wnt3a treatment increased the activation of the metabolic sensor Akt. Moreover, we observed an increase in the activity of hexokinase and in the glycolytic rate, and both processes were dependent on activation of the Akt pathway. Furthermore, we did not observe changes in the activity of glucose-6-phosphate dehydrogenase or in the pentose phosphate pathway. The effect of Wnt3a was independent of both the transcription of Wnt target genes and synaptic effects of Wnt3a. Together, our results suggest that Wnt signaling stimulates glucose utilization in cortical neurons through glycolysis to satisfy the high energy demand of these cells.

  16. Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling

    PubMed Central

    Delvendahl, Igor; Jablonski, Lukasz; Baade, Carolin; Matveev, Victor; Neher, Erwin; Hallermann, Stefan

    2015-01-01

    Fast synchronous neurotransmitter release at the presynaptic active zone is triggered by local Ca2+ signals, which are confined in their spatiotemporal extent by endogenous Ca2+ buffers. However, it remains elusive how rapid and reliable Ca2+ signaling can be sustained during repetitive release. Here, we established quantitative two-photon Ca2+ imaging in cerebellar mossy fiber boutons, which fire at exceptionally high rates. We show that endogenous fixed buffers have a surprisingly low Ca2+-binding ratio (∼15) and low affinity, whereas mobile buffers have high affinity. Experimentally constrained modeling revealed that the low endogenous buffering promotes fast clearance of Ca2+ from the active zone during repetitive firing. Measuring Ca2+ signals at different distances from active zones with ultra-high-resolution confirmed our model predictions. Our results lead to the concept that reduced Ca2+ buffering enables fast active zone Ca2+ signaling, suggesting that the strength of endogenous Ca2+ buffering limits the rate of synchronous synaptic transmission. PMID:26015575

  17. TAK1 regulates caspase 8 activation and necroptotic signaling via multiple cell death checkpoints

    PubMed Central

    Guo, Xiaoyun; Yin, Haifeng; Chen, Yi; Li, Lei; Li, Jing; Liu, Qinghang

    2016-01-01

    Necroptosis has emerged as a new form of programmed cell death implicated in a number of pathological conditions such as ischemic injury, neurodegenerative disease, and viral infection. Recent studies indicate that TGFβ-activated kinase 1 (TAK1) is nodal regulator of necroptotic cell death, although the underlying molecular regulatory mechanisms are not well defined. Here we reported that TAK1 regulates necroptotic signaling as well as caspase 8-mediated apoptotic signaling through both NFκB-dependent and -independent mechanisms. Inhibition of TAK1 promoted TNFα-induced cell death through the induction of RIP1 phosphorylation/activation and necrosome formation. Further, inhibition of TAK1 triggered two caspase 8 activation pathways through the induction of RIP1-FADD-caspase 8 complex as well as FLIP cleavage/degradation. Mechanistically, our data uncovered an essential role for the adaptor protein TNF receptor-associated protein with death domain (TRADD) in caspase 8 activation and necrosome formation triggered by TAK1 inhibition. Moreover, ablation of the deubiqutinase CYLD prevented both apoptotic and necroptotic signaling induced by TAK1 inhibition. Finally, blocking the ubiquitin-proteasome pathway prevented the degradation of key pro-survival signaling proteins and necrosome formation. Thus, we identified new regulatory mechanisms underlying the critical role of TAK1 in cell survival through regulation of multiple cell death checkpoints. Targeting key components of the necroptotic pathway (e.g., TRADD and CYLD) and the ubiquitin-proteasome pathway may represent novel therapeutic strategies for pathological conditions driven by necroptosis. PMID:27685625

  18. Electrochemical detection of protein kinase activity based on carboxypeptidase Y digestion triggered signal amplification.

    PubMed

    Yin, Huanshun; Wang, Xinxu; Guo, Yunlong; Zhou, Yunlei; Ai, Shiyun

    2015-04-15

    An effective assay method for monitoring protein kinase activity and screening inhibitors is greatly beneficial to kinase-related drug discovery, early diagnosis of diseases, and therapeutic effect evaluation. Herein, we develop a simple electrochemical method for detecting the activity of casein kinase II (CK2) based on phosphorylation against carboxypeptidase Y (CPY) digestion triggered signal amplification, where CK2 catalyzed phosphorylation event protects the substrate peptide from the digestion of CPY, maintains the repulsive force of the substrate peptide towards the redox probe, and results in a weak electrochemical signal. Whereas, without phosphorylation, the substrate peptide is digested by CPY and a strong electrochemical signal is obtained. The detection feasibility is demonstrated for the assay of CK2 activity with low detection limit of 0.047unit/mL. Moreover, the biosensor was used for the analysis of kinase inhibition. Based on the electrochemical signal dependent inhibitor concentration, the IC50 value of ellagic acid was estimated to be 39.77nM. The proposed method is also successfully applied to analyze CK2 activity in cell lysates, proving the applicability in complex biological samples.

  19. ASBESTOS-INDUCED ACTIVATION OF SIGNALING PATHWAYS IN HUMAN BRONCHIAL EPITHELIAL CELLS

    EPA Science Inventory

    Title: Asbestos-Induced Activation of Signaling Pathways in Human
    Bronchial Epithelial Cells

    X. Wang, MD 1, J. M. Samet, PhD 2 and A. J. Ghio, MD 2. 1 Center for
    Environmental Medicine, Asthma and Lung Biology, University of North
    Carolina, Chapel Hill, NC, Uni...

  20. Activation of Hh Signaling: A Critical Biological Consequence of ETS Gene Anomalies in Prostate Cancer

    DTIC Science & Technology

    2011-03-31

    consequence of ETS gene overexpression in prostate cells is increased expression and activity of Gli transcription factors that are normally induced by...Additionally, we identified Gli overexpression induces androgen-independent growth of prostate cancer cells and this action is mediated by...interaction between GLIs and androgen receptor (AR) which leads to activation of AR signaling under androgen-deprived conditions. 15. SUBJECT TERMS