Ethanol Inhibits High-Affinity Immunoglobulin E Receptor (FcεRI) Signaling in Mast Cells by Suppressing the Function of FcεRI-Cholesterol Signalosome

PubMed Central

Draberova, Lubica; Paulenda, Tomas; Halova, Ivana; Potuckova, Lucie; Bugajev, Viktor; Bambouskova, Monika; Tumova, Magda; Draber, Petr

2015-01-01

Ethanol has multiple effects on biochemical events in a variety of cell types, including the high-affinity immunoglobulin E receptor (FcεRI) signaling in antigen-activated mast cells. However, the underlying molecular mechanism remains unknown. To get better understanding of the effect of ethanol on FcεRI-mediated signaling we examined the effect of short-term treatment with non-toxic concentrations of ethanol on FcεRI signaling events in mouse bone marrow-derived mast cells. We found that 15 min exposure to ethanol inhibited antigen-induced degranulation, calcium mobilization, expression of proinflammatory cytokine genes (tumor necrosis factor-α, interleukin-6, and interleukin-13), and formation of reactive oxygen species in a dose-dependent manner. Removal of cellular cholesterol with methyl-β-cyclodextrin had a similar effect and potentiated some of the inhibitory effects of ethanol. In contrast, exposure of the cells to cholesterol-saturated methyl-β-cyclodextrin abolished in part the inhibitory effect of ethanol on calcium response and production of reactive oxygen species, supporting lipid-centric theories of ethanol action on the earliest stages of mast cell signaling. Further studies showed that exposure to ethanol and/or removal of cholesterol inhibited early FcεRI activation events, including tyrosine phosphorylation of the FcεRI β and γ subunits, SYK kinases, LAT adaptor protein, phospholipase Cγ, STAT5, and AKT and internalization of aggregated FcεRI. Interestingly, ethanol alone, and particularly in combination with methyl-β-cyclodextrin, enhanced phosphorylation of negative regulatory tyrosine 507 of LYN kinase. Finally, we found that ethanol reduced passive cutaneous anaphylactic reaction in mice, suggesting that ethanol also inhibits FcεRI signaling under in vivo conditions. The combined data indicate that ethanol interferes with early antigen-induced signaling events in mast cells by suppressing the function of FcεRI-cholesterol signalosomes at the plasma membrane. PMID:26658290

Gravitational Wave Detection of Compact Binaries Through Multivariate Analysis

NASA Astrophysics Data System (ADS)

Atallah, Dany Victor; Dorrington, Iain; Sutton, Patrick

2017-01-01

The first detection of gravitational waves (GW), GW150914, as produced by a binary black hole merger, has ushered in the era of GW astronomy. The detection technique used to find GW150914 considered only a fraction of the information available describing the candidate event: mainly the detector signal to noise ratios and chi-squared values. In hopes of greatly increasing detection rates, we want to take advantage of all the information available about candidate events. We employ a technique called Multivariate Analysis (MVA) to improve LIGO sensitivity to GW signals. MVA techniques are efficient ways to scan high dimensional data spaces for signal/noise classification. Our goal is to use MVA to classify compact-object binary coalescence (CBC) events composed of any combination of black holes and neutron stars. CBC waveforms are modeled through numerical relativity. Templates of the modeled waveforms are used to search for CBCs and quantify candidate events. Different MVA pipelines are under investigation to look for CBC signals and un-modelled signals, with promising results. One such MVA pipeline used for the un-modelled search can theoretically analyze far more data than the MVA pipelines currently explored for CBCs, potentially making a more powerful classifier. In principle, this extra information could improve the sensitivity to GW signals. We will present the results from our efforts to adapt an MVA pipeline used in the un-modelled search to classify candidate events from the CBC search.

Bimolecular fluorescence complementation: lighting up seven transmembrane domain receptor signalling networks

PubMed Central

Rose, Rachel H; Briddon, Stephen J; Holliday, Nicholas D

2010-01-01

There is increasing complexity in the organization of seven transmembrane domain (7TM) receptor signalling pathways, and in the ability of their ligands to modulate and direct this signalling. Underlying these events is a network of protein interactions between the 7TM receptors themselves and associated effectors, such as G proteins and β-arrestins. Bimolecular fluorescence complementation, or BiFC, is a technique capable of detecting these protein–protein events essential for 7TM receptor function. Fluorescent proteins, such as those from Aequorea victoria, are split into two non-fluorescent halves, which then tag the proteins under study. On association, these fragments refold and regenerate a mature fluorescent protein, producing a BiFC signal indicative of complex formation. Here, we review the experimental criteria for successful application of BiFC, considered in the context of 7TM receptor signalling events such as receptor dimerization, G protein and β-arrestin signalling. The advantages and limitations of BiFC imaging are compared with alternative resonance energy transfer techniques. We show that the essential simplicity of the fluorescent BiFC measurement allows high-content and advanced imaging applications, and that it can probe more complex multi-protein interactions alone or in combination with resonance energy transfer. These capabilities suggest that BiFC techniques will become ever more useful in the analysis of ligand and 7TM receptor pharmacology at the molecular level of protein–protein interactions. This article is part of a themed section on Imaging in Pharmacology. To view the editorial for this themed section visit http://dx.doi.org/10.1111/j.1476-5381.2010.00685.x PMID:20015298

An FPGA-based trigger for the phase II of the MEG experiment

NASA Astrophysics Data System (ADS)

Baldini, A.; Bemporad, C.; Cei, F.; Galli, L.; Grassi, M.; Morsani, F.; Nicolò, D.; Ritt, S.; Venturini, M.

2016-07-01

For the phase II of MEG, we are going to develop a combined trigger and DAQ system. Here we focus on the former side, which operates an on-line reconstruction of detector signals and event selection within 450 μs from event occurrence. Trigger concentrator boards (TCB) are under development to gather data from different crates, each connected to a set of detector channels, to accomplish higher-level algorithms to issue a trigger in the case of a candidate signal event. We describe the major features of the new system, in comparison with phase I, as well as its performances in terms of selection efficiency and background rejection.

Modeling Array Stations in SIG-VISA

NASA Astrophysics Data System (ADS)

Ding, N.; Moore, D.; Russell, S.

2013-12-01

We add support for array stations to SIG-VISA, a system for nuclear monitoring using probabilistic inference on seismic signals. Array stations comprise a large portion of the IMS network; they can provide increased sensitivity and more accurate directional information compared to single-component stations. Our existing model assumed that signals were independent at each station, which is false when lots of stations are close together, as in an array. The new model removes that assumption by jointly modeling signals across array elements. This is done by extending our existing Gaussian process (GP) regression models, also known as kriging, from a 3-dimensional single-component space of events to a 6-dimensional space of station-event pairs. For each array and each event attribute (including coda decay, coda height, amplitude transfer and travel time), we model the joint distribution across array elements using a Gaussian process that learns the correlation lengthscale across the array, thereby incorporating information of array stations into the probabilistic inference framework. To evaluate the effectiveness of our model, we perform ';probabilistic beamforming' on new events using our GP model, i.e., we compute the event azimuth having highest posterior probability under the model, conditioned on the signals at array elements. We compare the results from our probabilistic inference model to the beamforming currently performed by IMS station processing.

CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation.

PubMed

Tang, Tiantian; Lang, Xueting; Xu, Congfei; Wang, Xiaqiong; Gong, Tao; Yang, Yanqing; Cui, Jun; Bai, Li; Wang, Jun; Jiang, Wei; Zhou, Rongbin

2017-08-04

The NLRP3 inflammasome can sense different pathogens or danger signals, and has been reported to be involved in the development of many human diseases. Potassium efflux and mitochondrial damage are both reported to mediate NLRP3 inflammasome activation, but the underlying, orchestrating signaling events are still unclear. Here we show that chloride intracellular channels (CLIC) act downstream of the potassium efflux-mitochondrial reactive oxygen species (ROS) axis to promote NLRP3 inflammasome activation. NLRP3 agonists induce potassium efflux, which causes mitochondrial damage and ROS production. Mitochondrial ROS then induces the translocation of CLICs to the plasma membrane for the induction of chloride efflux to promote NEK7-NLRP3 interaction, inflammasome assembly, caspase-1 activation, and IL-1β secretion. Thus, our results identify CLICs-dependent chloride efflux as an essential and proximal upstream event for NLRP3 activation.The NLRP3 inflammasome is key to the regulation of innate immunity against pathogens or stress, but the underlying signaling regulation is still unclear. Here the authors show that chloride intracellular channels (CLIC) interface between mitochondria stress and inflammasome activation to modulate inflammatory responses.

Study of the early signal perturbations due to GJ and Elves using the LWPC code

NASA Astrophysics Data System (ADS)

Nait Amor, Samir; Ghalila, Hassen; Bouderba, Yasmina

2015-04-01

Early events are a Very Low Frequencies (VLF) signal perturbations recorded during a lightning activity. The properties of these signal perturbations and their association to the lightning peak current and/or Transient Luminous Events (TLEs) were widely studied. In a recently analysis a new early signal perturbations whose recovery time persists for several minutes were discovered. The underlying cause of these events is still unclear. In a recently published work, these events were attributed to the lightning peak current and the type of associated TLE. In others, and newly published papers, analyzes were done where all kind of early events were considered. Statistical results showed that the occurrence of long recovery events is independent of the lightning current amplitude and/or TLEs type. To understand which is the main cause of these events, we analyzed two types of early signal perturbations: One was a typical event (~200s time duration) in association with a Gigantic Jet and the second was a long recovery event in association with an elve recorded on December 12 2009 during the EuroSprite campaign. In addition to the VLF signal analysis, we used the Long Wave Propagation Capability (LWPC) code to simulate the unperturbed and perturbed signal parameters (amplitude and phase), to determine the signal modes attenuation coefficient and then to infer the electron density increases in the disturbed region. The results showed that the reference height was reduced from its ambient value (87km) to 66.4 km in the case of the GJ and 74.3 km for the elve. These reference heights decreases affected the propagating signal at the disturbed region by increasing the modes attenuation coefficient. Effectively, the number of modes was reduced from 28 at ambient condition to 9 modes (in the case of GJ) and 17 (in the case of elve). This high attenuation of modes leads to the appearance of null signal perturbations positions due to the interferences. Between two null positions the signal perturbation was negative (or decreasing) and sometimes positive (or increasing). It was also observed from the LWPC code results that the perturbation amplitude was maximum when the perturbed and unperturbed signals were in phase. Thus the main reason of these observations is the modal structure of the signal at the disturbed region and the receiver location. The electron density increases reached 104 cm-3 at 85 km independently on TLE kind. By the use of the signal perturbation parameters due to the long recovery event and the LWPC code, a recovery time profile of the electron density at each height below 87 km is obtained. The first order exponential decay fit gives different recovery constants depending on the height. This is in good agreement with the atmospheric model where the loss terms rates vary with altitude.

Low-mass dark matter search using ionization signals in XENON100

NASA Astrophysics Data System (ADS)

Aprile, E.; Aalbers, J.; Agostini, F.; Alfonsi, M.; Amaro, F. D.; Anthony, M.; Arneodo, F.; Barrow, P.; Baudis, L.; Bauermeister, B.; Benabderrahmane, M. L.; Berger, T.; Breur, P. A.; Brown, A.; Brown, E.; Bruenner, S.; Bruno, G.; Budnik, R.; Buss, A.; Bütikofer, L.; Cardoso, J. M. R.; Cervantes, M.; Cichon, D.; Coderre, D.; Colijn, A. P.; Conrad, J.; Cussonneau, J. P.; Decowski, M. P.; de Perio, P.; di Gangi, P.; di Giovanni, A.; Duchovni, E.; Ferella, A. D.; Fieguth, A.; Franco, D.; Fulgione, W.; Galloway, M.; Garbini, M.; Geis, C.; Goetzke, L. W.; Greene, Z.; Grignon, C.; Gross, E.; Hasterok, C.; Hogenbirk, E.; Itay, R.; Kaminsky, B.; Kessler, G.; Kish, A.; Landsman, H.; Lang, R. F.; Levinson, L.; Le Calloch, M.; Levy, C.; Linde, F.; Lindemann, S.; Lindner, M.; Lopes, J. A. M.; Lyashenko, A.; Manfredini, A.; Marrodán Undagoitia, T.; Masbou, J.; Massoli, F. V.; Masson, D.; Mayani, D.; Melgarejo Fernandez, A. J.; Meng, Y.; Messina, M.; Micheneau, K.; Miguez, B.; Molinario, A.; Murra, M.; Naganoma, J.; Oberlack, U.; Orrigo, S. E. A.; Pakarha, P.; Pelssers, B.; Persiani, R.; Piastra, F.; Pienaar, J.; Plante, G.; Priel, N.; Rauch, L.; Reichard, S.; Reuter, C.; Rizzo, A.; Rosendahl, S.; Rupp, N.; Dos Santos, J. M. F.; Sartorelli, G.; Scheibelhut, M.; Schindler, S.; Schreiner, J.; Schumann, M.; Scotto Lavina, L.; Selvi, M.; Shagin, P.; Simgen, H.; Stein, A.; Thers, D.; Tiseni, A.; Trinchero, G.; Tunnell, C. D.; von Sivers, M.; Wall, R.; Wang, H.; Weber, M.; Wei, Y.; Weinheimer, C.; Wulf, J.; Zhang, Y.; Xenon Collaboration

2016-11-01

We perform a low-mass dark matter search using an exposure of 30 kg ×yr with the XENON100 detector. By dropping the requirement of a scintillation signal and using only the ionization signal to determine the interaction energy, we lowered the energy threshold for detection to 0.7 keV for nuclear recoils. No dark matter detection can be claimed because a complete background model cannot be constructed without a primary scintillation signal. Instead, we compute an upper limit on the WIMP-nucleon scattering cross section under the assumption that every event passing our selection criteria could be a signal event. Using an energy interval from 0.7 keV to 9.1 keV, we derive a limit on the spin-independent WIMP-nucleon cross section that excludes WIMPs with a mass of 6 GeV /c2 above 1.4 ×10-41 cm2 at 90% confidence level.

Seismic Characterization of EGS Reservoirs

NASA Astrophysics Data System (ADS)

Templeton, D. C.; Pyle, M. L.; Matzel, E.; Myers, S.; Johannesson, G.

2014-12-01

To aid in the seismic characterization of Engineered Geothermal Systems (EGS), we enhance the traditional microearthquake detection and location methodologies at two EGS systems. We apply the Matched Field Processing (MFP) seismic imaging technique to detect new seismic events using known discrete microearthquake sources. Events identified using MFP are typically smaller magnitude events or events that occur within the coda of a larger event. Additionally, we apply a Bayesian multiple-event seismic location algorithm, called MicroBayesLoc, to estimate the 95% probability ellipsoids for events with high signal-to-noise ratios (SNR). Such probability ellipsoid information can provide evidence for determining if a seismic lineation could be real or simply within the anticipated error range. We apply this methodology to the Basel EGS data set and compare it to another EGS dataset. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Event-Triggered Fault Detection of Nonlinear Networked Systems.

PubMed

Li, Hongyi; Chen, Ziran; Wu, Ligang; Lam, Hak-Keung; Du, Haiping

2017-04-01

This paper investigates the problem of fault detection for nonlinear discrete-time networked systems under an event-triggered scheme. A polynomial fuzzy fault detection filter is designed to generate a residual signal and detect faults in the system. A novel polynomial event-triggered scheme is proposed to determine the transmission of the signal. A fault detection filter is designed to guarantee that the residual system is asymptotically stable and satisfies the desired performance. Polynomial approximated membership functions obtained by Taylor series are employed for filtering analysis. Furthermore, sufficient conditions are represented in terms of sum of squares (SOSs) and can be solved by SOS tools in MATLAB environment. A numerical example is provided to demonstrate the effectiveness of the proposed results.

Digital Electronics for Nuclear Physics Experiments

NASA Astrophysics Data System (ADS)

Skulski, Wojtek; Hunter, David; Druszkiewicz, Eryk; Khaitan, Dev Ashish; Yin, Jun; Wolfs, Frank; SkuTek Instrumentation Team; Department of Physics; Astronomy, University of Rochester Team

2015-10-01

Future detectors in nuclear physics will use signal sampling as one of primary techniques of data acquisition. Using the digitized waveforms, the electronics can select events based on pulse shape, total energy, multiplicity, and the hit pattern. The DAQ for the LZ Dark Matter detector, now under development in Rochester, is a good example of the power of digital signal processing. This system, designed around 32-channel, FPGA-based, digital signal processors collects data from more than one thousand channels. The solutions developed for this DAQ can be applied to nuclear physics experiments. Supported by the Department of Energy Office of Science under Grant DE-SC0009543.

Using Boosting Decision Trees in Gravitational Wave Searches triggered by Gamma-ray Bursts

NASA Astrophysics Data System (ADS)

Zuraw, Sarah; LIGO Collaboration

2015-04-01

The search for gravitational wave bursts requires the ability to distinguish weak signals from background detector noise. Gravitational wave bursts are characterized by their transient nature, making them particularly difficult to detect as they are similar to non-Gaussian noise fluctuations in the detector. The Boosted Decision Tree method is a powerful machine learning algorithm which uses Multivariate Analysis techniques to explore high-dimensional data sets in order to distinguish between gravitational wave signal and background detector noise. It does so by training with known noise events and simulated gravitational wave events. The method is tested using waveform models and compared with the performance of the standard gravitational wave burst search pipeline for Gamma-ray Bursts. It is shown that the method is able to effectively distinguish between signal and background events under a variety of conditions and over multiple Gamma-ray Burst events. This example demonstrates the usefulness and robustness of the Boosted Decision Tree and Multivariate Analysis techniques as a detection method for gravitational wave bursts. LIGO, UMass, PREP, NEGAP.

Reference set for performance testing of pediatric vaccine safety signal detection methods and systems.

PubMed

Brauchli Pernus, Yolanda; Nan, Cassandra; Verstraeten, Thomas; Pedenko, Mariia; Osokogu, Osemeke U; Weibel, Daniel; Sturkenboom, Miriam; Bonhoeffer, Jan

2016-12-12

Safety signal detection in spontaneous reporting system databases and electronic healthcare records is key to detection of previously unknown adverse events following immunization. Various statistical methods for signal detection in these different datasources have been developed, however none are geared to the pediatric population and none specifically to vaccines. A reference set comprising pediatric vaccine-adverse event pairs is required for reliable performance testing of statistical methods within and across data sources. The study was conducted within the context of the Global Research in Paediatrics (GRiP) project, as part of the seventh framework programme (FP7) of the European Commission. Criteria for the selection of vaccines considered in the reference set were routine and global use in the pediatric population. Adverse events were primarily selected based on importance. Outcome based systematic literature searches were performed for all identified vaccine-adverse event pairs and complemented by expert committee reports, evidence based decision support systems (e.g. Micromedex), and summaries of product characteristics. Classification into positive (PC) and negative control (NC) pairs was performed by two independent reviewers according to a pre-defined algorithm and discussed for consensus in case of disagreement. We selected 13 vaccines and 14 adverse events to be included in the reference set. From a total of 182 vaccine-adverse event pairs, we classified 18 as PC, 113 as NC and 51 as unclassifiable. Most classifications (91) were based on literature review, 45 were based on expert committee reports, and for 46 vaccine-adverse event pairs, an underlying pathomechanism was not plausible classifying the association as NC. A reference set of vaccine-adverse event pairs was developed. We propose its use for comparing signal detection methods and systems in the pediatric population. Published by Elsevier Ltd.

Analysis of strong scintillation events by using GPS data at low latitudes

NASA Astrophysics Data System (ADS)

Forte, Biagio; Jakowski, Norbert; Wilken, Volker

2010-05-01

Drifting structures charaterised by inhomogeneities in the spatial electron density distribution at ionospheric heights originate scintillation of radio waves propagating through. The fractional electron density fluctuations and the corresponding scintillation levels may reach extreme values at low latitudes during high solar activity. Strong scintillation events have disruptive effects on a number of technological applications. In particular, operations and services based on GPS signals and receivers may experience severe disruption due to a significant degradation of the signal-to-noise ratio, eventually leading to signal loss of lock. Experimental scintillation data collected in the Asian sector at low latitudes by means of a GPS dual frequency receiver under moderate solar activity (2006) have been analysed. The GPS receiver is particularly modified in firmware in order to record power estimates on the C/A code as well as on the carriers L1 and L2. Strong scintillation activity is recorded in the post-sunset period (saturating S4 and SI as high as 20 dB). An overview of these events is presented, by taking into account scintillation impact on the signal intensity, phase, and dynamics. In particular, the interpretation of these events based on a refined scattering theory is provided with possible consequences for standard scintillation models.

Characteristics of High Latitude Ionosphere Scintillations

NASA Astrophysics Data System (ADS)

Morton, Y.

2012-12-01

As we enter a new solar maximum period, global navigation satellite systems (GNSS) receivers, especially the ones operating in high latitude and equatorial regions, are facing an increasing threat from ionosphere scintillations. The increased solar activities, however, also offer a great opportunity to collect scintillation data to characterize scintillation signal parameters and ionosphere irregularities. While there are numerous GPS receivers deployed around the globe to monitor ionosphere scintillations, most of them are commercial receivers whose signal processing mechanisms are not designed to operate under ionosphere scintillation. As a result, they may distort scintillation signal parameters or lose lock of satellite signals under strong scintillations. Since 2008, we have established and continuously improved a unique GNSS receiver array at HAARP, Alaska. The array contains high ends commercial receivers and custom RF front ends which can be automatically triggered to collect high quality GPS and GLONASS satellite signals during controlled heating experiments and natural scintillation events. Custom designed receiver signal tracking algorithms aim to preserve true scintillation signatures are used to process the raw RF samples. Signal strength, carrier phase, and relative TEC measurements generated by the receiver array since its inception have been analyzed to characterize high latitude scintillation phenomena. Daily, seasonal, and solar events dependency of scintillation occurrence, spectral contents of scintillation activities, and plasma drifts derived from these measurements will be presented. These interesting results demonstrate the feasibility and effectiveness of our experimental data collection system in providing insightful details of ionosphere responses to active perturbations and natural disturbances.

Adaptive Neural Network-Based Event-Triggered Control of Single-Input Single-Output Nonlinear Discrete-Time Systems.

PubMed

Sahoo, Avimanyu; Xu, Hao; Jagannathan, Sarangapani

2016-01-01

This paper presents a novel adaptive neural network (NN) control of single-input and single-output uncertain nonlinear discrete-time systems under event sampled NN inputs. In this control scheme, the feedback signals are transmitted, and the NN weights are tuned in an aperiodic manner at the event sampled instants. After reviewing the NN approximation property with event sampled inputs, an adaptive state estimator (SE), consisting of linearly parameterized NNs, is utilized to approximate the unknown system dynamics in an event sampled context. The SE is viewed as a model and its approximated dynamics and the state vector, during any two events, are utilized for the event-triggered controller design. An adaptive event-trigger condition is derived by using both the estimated NN weights and a dead-zone operator to determine the event sampling instants. This condition both facilitates the NN approximation and reduces the transmission of feedback signals. The ultimate boundedness of both the NN weight estimation error and the system state vector is demonstrated through the Lyapunov approach. As expected, during an initial online learning phase, events are observed more frequently. Over time with the convergence of the NN weights, the inter-event times increase, thereby lowering the number of triggered events. These claims are illustrated through the simulation results.

Neural Dynamics Underlying Event-Related Potentials

NASA Technical Reports Server (NTRS)

Shah, Ankoor S.; Bressler, Steven L.; Knuth, Kevin H.; Ding, Ming-Zhou; Mehta, Ashesh D.; Ulbert, Istvan; Schroeder, Charles E.

2003-01-01

There are two opposing hypotheses about the brain mechanisms underlying sensory event-related potentials (ERPs). One holds that sensory ERPs are generated by phase resetting of ongoing electroencephalographic (EEG) activity, and the other that they result from signal averaging of stimulus-evoked neural responses. We tested several contrasting predictions of these hypotheses by direct intracortical analysis of neural activity in monkeys. Our findings clearly demonstrate evoked response contributions to the sensory ERP in the monkey, and they suggest the likelihood that a mixed (Evoked/Phase Resetting) model may account for the generation of scalp ERPs in humans.

Prescription-event monitoring: developments in signal detection.

PubMed

Ferreira, Germano

2007-01-01

Prescription-event monitoring (PEM) is a non-interventional intensive method for post-marketing drug safety monitoring of newly licensed medicines. PEM studies are cohort studies where exposure is obtained from a centralised service and outcomes from simple questionnaires completed by general practitioners. Follow-up forms are sent for selected events. Because PEM captures all events and not only the suspected adverse drug reactions, PEM cohorts potentially differ in respect to the distribution of number of events per person depending on the nature of the drug under study. This variance can be related either with the condition for which the drug is prescribed (e.g. a condition causing high morbidity will have, in average, a higher number of events per person compared with a condition with lower morbidity) or with the drug effect itself. This paper describes an exploratory investigation of the distortion caused by product-related variations of the number of events to the interpretation of the proportional reporting ratio (PRR) values ("the higher the PRR, the greater the strength of the signal") computed using drug-cohort data. We studied this effect by assessing the agreement between the PRR based on events (event of interest vs all other events) and PRR based on cases (cases with the event of interest vs cases with any other events). PRR were calculated for all combinations reported to ten selected drugs against a comparator of 81 other drugs. Three of the ten drugs had a cohort with an apparent higher proportion of patients with lower number of events. The PRRs based on events were systematically higher than the PRR based on cases for the combinations reported to these three drugs. Additionally, when applying the threshold criteria for signal screening (n > or =3, PRR > or =1.5 and Chi-squared > or =4), the binary agreement was generally high but apparently lower for these three drugs. In conclusion, the distribution of events per patient in drug cohorts shall be examined when comparing the 'strength of the signals' across drugs using PRR values. Further research will be required to address the sensitivity and specificity of the two ways of calculating PRR using data derived from drug cohorts.

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

PubMed

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

2016-10-13

Disruption of the biological rhythm in patients with bipolar disorder is a known risk factor for a switch in mood. This case study describes how modern techniques using ambulatory assessment of sleep parameters can help in signalling a mood switch and start early treatment. We studied a 40-year-old woman with bipolar disorder experiencing a life event while wearing an actigraph to measure sleep-wake parameters. The night after the life event the woman had sleep later and shorter sleep duration. Adequate response of both the woman and the treating psychiatrist resulted in two normal nights with the use of 1 mg lorazepam, possibly preventing further mood disturbances. Ambulatory assessment of the biological rhythm can function as an add-on to regular signalling plans for prevention of episodes in patients with bipolar disorder. More research should be conducted to validate clinical applicability, proper protocols and to understand underlying mechanisms. 2016 BMJ Publishing Group Ltd.

Electronic system

DOEpatents

Robison, G H; Dickson, J F

1960-11-15

An electronic system is designed for indicating the occurrence of a plurality of electrically detectable events within predetermined time intervals. The system comprises separate input means electrically associated with the events under observation an electronic channel associated with each input means, including control means and indicating means; timing means adapted to apply a signal from the input means after a predetermined time to the control means to deactivate each of the channels; and means for resetting the system to its initial condition after the observation of each group of events. (D.L.C.)

Microseismic Event Grouping Based on PageRank Linkage at the Newberry Volcano Geothermal Site

NASA Astrophysics Data System (ADS)

Aguiar, A. C.; Myers, S. C.

2016-12-01

The Newberry Volcano DOE FORGE site in Central Oregon has been stimulated two times using high-pressure fluid injection to study the Enhanced Geothermal Systems (EGS) technology. Several hundred microseismic events were generated during the first stimulation in the fall of 2012. Initial locations of this microseismicity do not show well defined subsurface structure in part because event location uncertainties are large (Foulger and Julian, 2013). We focus on this stimulation to explore the spatial and temporal development of microseismicity, which is key to understanding how subsurface stimulation modifies stress, fractures rock, and increases permeability. We use PageRank, Google's initial search algorithm, to determine connectivity within the events (Aguiar and Beroza, 2014) and assess signal-correlation topology for the micro-earthquakes. We then use this information to create signal families and compare these to the spatial and temporal proximity of associated earthquakes. We relocate events within families (identified by PageRank linkage) using the Bayesloc approach (Myers et al., 2007). Preliminary relocations show tight spatial clustering of event families as well as evidence of events relocating to a different cluster than originally reported. We also find that signal similarity (linkage) at several stations, not just one or two, is needed in order to determine that events are in close proximity to one another. We show that indirect linkage of signals using PageRank is a reliable way to increase the number of events that are confidently determined to be similar to one another, which may lead to efficient and effective grouping of earthquakes with similar physical characteristics, such as focal mechanisms and stress drop. Our ultimate goal is to determine whether changes in the state of stress and/or changes in the generation of subsurface fracture networks can be detected using PageRank topology as well as aid in the event relocation to obtain more accurate subsurface structure. Prepared by LLNL under Contract DE-AC52-07NA27344. LLNL-ABS-699142.

Amplification of seismic waves beneath active volcanoes

NASA Astrophysics Data System (ADS)

Navon, O.; Lensky, N. G.; Collier, L.; Neuberg, J.; Lyakhovsky, V.

2003-04-01

Long-period (LP) seismic events are typical of many volcanoes and are attributed to energy leaking from waves traveling through the volcanic conduit or along the conduit - country-rock interface. The LP events are triggered locally, at the volcanic edifice, but the source of energy for the formation of tens of events per day is not clear. Energy may be supplied by volatile-release from a supersaturated melt. If bubbles are present in equilibrium with the melt in the conduit, and the melt is suddenly decompressed, transfer of volatiles from the supersaturated melt into the bubbles transforms stored potential energy into expansion work. For example, small dome collapses may decompress the conduit by a few bars and lead to solubility decrease, exsolution of volatiles and, consequently, to work done by the expansion of the bubbles under pressure. This energy is released over a timescale that is similar to that of LP events and may amplify the original weak seismic signals associated with the collapse. Using the formulation of Lensky et al. (2002), following the decompression, when the transfer of volatiles into bubbles is fast enough, expansion accelerates and the bulk viscosity of the bubbly magma is negative. New calculations show that under such conditions a sinusoidal P-wave is amplified. We note that seismic waves created by tectonic earthquakes that are not associated with net decompression, do not lead to net release of volatiles or to net expansion. In this case, the bulk viscosity is positive and waves traveling through the magma should attenuate. The proposed model explains how weak seismic signals may be amplified as they travel through a conduit that contains supersaturated bubbly magma. It provides the general framework for amplifying volcanic seismicity such as the signals associated with long-period events.

Safety first: Instrumentality for reaching safety determines attention allocation under threat.

PubMed

Vogt, Julia; Koster, Ernst H W; De Houwer, Jan

2017-04-01

Theories of attention to emotional information suggest that attentional processes prioritize threatening information. In this article, we suggest that attention will prioritize the events that are most instrumental to a goal in any given context, which in threatening situations is typically reaching safety. To test our hypotheses, we used an attentional cueing paradigm that contained cues signaling imminent threat (i.e., aversive noises) as well as cues that allowed participants to avoid threat (instrumental safety signals). Correct reactions to instrumental safety signals seemingly allowed participants to lower the presentation rate of the threat. Experiment 1 demonstrates that attention prioritizes instrumental safety signals over threat signals. Experiment 2 replicates this finding and additionally compares instrumental safety signals to other action-relevant signals controlling for action relevance as cause of the effects. Experiment 3 demonstrates that when actions toward threat signals permit to avoid threat, attention prioritizes threat signals. Taken together, these results support the view that instrumentality for reaching safety determines the allocation of attention under threat. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Eventogram: A Visual Representation of Main Events in Biomedical Signals.

PubMed

Elgendi, Mohamed

2016-09-22

Biomedical signals carry valuable physiological information and many researchers have difficulty interpreting and analyzing long-term, one-dimensional, quasi-periodic biomedical signals. Traditionally, biomedical signals are analyzed and visualized using periodogram, spectrogram, and wavelet methods. However, these methods do not offer an informative visualization of main events within the processed signal. This paper attempts to provide an event-related framework to overcome the drawbacks of the traditional visualization methods and describe the main events within the biomedical signal in terms of duration and morphology. Electrocardiogram and photoplethysmogram signals are used in the analysis to demonstrate the differences between the traditional visualization methods, and their performance is compared against the proposed method, referred to as the " eventogram " in this paper. The proposed method is based on two event-related moving averages that visualizes the main time-domain events in the processed biomedical signals. The traditional visualization methods were unable to find dominant events in processed signals while the eventogram was able to visualize dominant events in signals in terms of duration and morphology. Moreover, eventogram -based detection algorithms succeeded with detecting main events in different biomedical signals with a sensitivity and positive predictivity >95%. The output of the eventogram captured unique patterns and signatures of physiological events, which could be used to visualize and identify abnormal waveforms in any quasi-periodic signal.

Subcellular Redox Targeting: Bridging in Vitro and in Vivo Chemical Biology.

PubMed

Long, Marcus J C; Poganik, Jesse R; Ghosh, Souradyuti; Aye, Yimon

2017-03-17

Networks of redox sensor proteins within discrete microdomains regulate the flow of redox signaling. Yet, the inherent reactivity of redox signals complicates the study of specific redox events and pathways by traditional methods. Herein, we review designer chemistries capable of measuring flux and/or mimicking subcellular redox signaling at the cellular and organismal level. Such efforts have begun to decipher the logic underlying organelle-, site-, and target-specific redox signaling in vitro and in vivo. These data highlight chemical biology as a perfect gateway to interrogate how nature choreographs subcellular redox chemistry to drive precision redox biology.

Bayesian hierarchical modeling for detecting safety signals in clinical trials.

PubMed

Xia, H Amy; Ma, Haijun; Carlin, Bradley P

2011-09-01

Detection of safety signals from clinical trial adverse event data is critical in drug development, but carries a challenging statistical multiplicity problem. Bayesian hierarchical mixture modeling is appealing for its ability to borrow strength across subgroups in the data, as well as moderate extreme findings most likely due merely to chance. We implement such a model for subject incidence (Berry and Berry, 2004 ) using a binomial likelihood, and extend it to subject-year adjusted incidence rate estimation under a Poisson likelihood. We use simulation to choose a signal detection threshold, and illustrate some effective graphics for displaying the flagged signals.

Rewiring of auxin signaling under persistent shade.

PubMed

Pucciariello, Ornella; Legris, Martina; Costigliolo Rojas, Cecilia; Iglesias, María José; Hernando, Carlos Esteban; Dezar, Carlos; Vazquez, Martín; Yanovsky, Marcelo J; Finlayson, Scott A; Prat, Salomé; Casal, Jorge J

2018-05-22

Light cues from neighboring vegetation rapidly initiate plant shade-avoidance responses. Despite our detailed knowledge of the early steps of this response, the molecular events under prolonged shade are largely unclear. Here we show that persistent neighbor cues reinforce growth responses in addition to promoting auxin-responsive gene expression in Arabidopsis and soybean. However, while the elevation of auxin levels is well established as an early event, in Arabidopsis , the response to prolonged shade occurs when auxin levels have declined to the prestimulation values. Remarkably, the sustained low activity of phytochrome B under prolonged shade led to ( i ) decreased levels of PHYTOCHROME INTERACTING FACTOR 4 (PIF4) in the cotyledons (the organs that supply auxin) along with increased levels in the vascular tissues of the stem, ( ii ) elevated expression of the PIF4 targets INDOLE-3-ACETIC ACID 19 ( IAA19 ) and IAA29 , which in turn reduced the expression of the growth-repressive IAA17 regulator, ( iii ) reduced abundance of AUXIN RESPONSE FACTOR 6, ( iv ) reduced expression of MIR393 and increased abundance of its targets, the auxin receptors, and ( v ) elevated auxin signaling as indicated by molecular markers. Mathematical and genetic analyses support the physiological role of this system-level rearrangement. We propose that prolonged shade rewires the connectivity between light and auxin signaling to sustain shade avoidance without enhanced auxin levels.

Advanced Geospatial Hydrodynamic Signals Analysis for Tsunami Event Detection and Warning

NASA Astrophysics Data System (ADS)

Arbab-Zavar, Banafshe; Sabeur, Zoheir

2013-04-01

Current early tsunami warning can be issued upon the detection of a seismic event which may occur at a given location offshore. This also provides an opportunity to predict the tsunami wave propagation and run-ups at potentially affected coastal zones by selecting the best matching seismic event from a database of pre-computed tsunami scenarios. Nevertheless, it remains difficult and challenging to obtain the rupture parameters of the tsunamigenic earthquakes in real time and simulate the tsunami propagation with high accuracy. In this study, we propose a supporting approach, in which the hydrodynamic signal is systematically analysed for traces of a tsunamigenic signal. The combination of relatively low amplitudes of a tsunami signal at deep waters and the frequent occurrence of background signals and noise contributes to a generally low signal to noise ratio for the tsunami signal; which in turn makes the detection of this signal difficult. In order to improve the accuracy and confidence of detection, a re-identification framework in which a tsunamigenic signal is detected via the scan of a network of hydrodynamic stations with water level sensing is performed. The aim is to attempt the re-identification of the same signatures as the tsunami wave spatially propagates through the hydrodynamic stations sensing network. The re-identification of the tsunamigenic signal is technically possible since the tsunami signal at the open ocean itself conserves its birthmarks relating it to the source event. As well as supporting the initial detection and improving the confidence of detection, a re-identified signal is indicative of the spatial range of the signal, and thereby it can be used to facilitate the identification of certain background signals such as wind waves which do not have as large a spatial reach as tsunamis. In this paper, the proposed methodology for the automatic detection of tsunamigenic signals has been achieved using open data from NOAA with a recorded tsunami event in the Pacific Ocean. The new approach will be tested in the future on other oceanic regions including the Mediteranean Sea and North East Atlantic Ocean zones. Both authors acknowledge that the current research is currently conducted under the TRIDEC IP FP7 project[1] which involves the development of a system of systems for collaborative, complex and critical decision-support in evolving crises. [1] TRIDEC IP ICT-2009.4.3 Intelligent Information Management Project Reference: 258723. http://www.tridec-online.eu/home

Fetal heart rate deceleration detection using a discrete cosine transform implementation of singular spectrum analysis.

PubMed

Warrick, P A; Precup, D; Hamilton, E F; Kearney, R E

2007-01-01

To develop a singular-spectrum analysis (SSA) based change-point detection algorithm applicable to fetal heart rate (FHR) monitoring to improve the detection of deceleration events. We present a method for decomposing a signal into near-orthogonal components via the discrete cosine transform (DCT) and apply this in a novel online manner to change-point detection based on SSA. The SSA technique forms models of the underlying signal that can be compared over time; models that are sufficiently different indicate signal change points. To adapt the algorithm to deceleration detection where many successive similar change events can occur, we modify the standard SSA algorithm to hold the reference model constant under such conditions, an approach that we term "base-hold SSA". The algorithm is applied to a database of 15 FHR tracings that have been preprocessed to locate candidate decelerations and is compared to the markings of an expert obstetrician. Of the 528 true and 1285 false decelerations presented to the algorithm, the base-hold approach improved on standard SSA, reducing the number of missed decelerations from 64 to 49 (21.9%) while maintaining the same reduction in false-positives (278). The standard SSA assumption that changes are infrequent does not apply to FHR analysis where decelerations can occur successively and in close proximity; our base-hold SSA modification improves detection of these types of event series.

Shallow repeating seismic events under an alpine glacier at Mount Rainier, Washington, USA

USGS Publications Warehouse

Thelen, Weston A.; Allstadt, Kate E.; De Angelis, Silvio; Malone, Stephen D.; Moran, Seth C.; Vidale, John

2013-01-01

We observed several swarms of repeating low-frequency (1–5 Hz) seismic events during a 3 week period in May–June 2010, near the summit of Mount Rainier, Washington, USA, that likely were a result of stick–slip motion at the base of alpine glaciers. The dominant set of repeating events ('multiplets') featured >4000 individual events and did not exhibit daytime variations in recurrence interval or amplitude. Volcanoes and glaciers around the world are known to produce seismic signals with great variability in both frequency content and size. The low-frequency character and periodic recurrence of the Mount Rainier multiplets mimic long-period seismicity often seen at volcanoes, particularly during periods of unrest. However, their near-surface location, lack of common spectral peaks across the recording network, rapid attenuation of amplitudes with distance, and temporal correlation with weather systems all indicate that ice-related source mechanisms are the most likely explanation. We interpret the low-frequency character of these multiplets to be the result of trapping of seismic energy under glacial ice as it propagates through the highly heterogeneous and attenuating volcanic material. The Mount Rainier multiplet sequences underscore the difficulties in differentiating low-frequency signals due to glacial processes from those caused by volcanic processes on glacier-clad volcanoes.

Molecular mechanisms underlying phosphate sensing, signaling, and adaptation in plants.

PubMed

Zhang, Zhaoliang; Liao, Hong; Lucas, William J

2014-03-01

As an essential plant macronutrient, the low availability of phosphorus (P) in most soils imposes serious limitation on crop production. Plants have evolved complex responsive and adaptive mechanisms for acquisition, remobilization and recycling of phosphate (Pi) to maintain P homeostasis. Spatio-temporal molecular, physiological, and biochemical Pi deficiency responses developed by plants are the consequence of local and systemic sensing and signaling pathways. Pi deficiency is sensed locally by the root system where hormones serve as important signaling components in terms of developmental reprogramming, leading to changes in root system architecture. Root-to-shoot and shoot-to-root signals, delivered through the xylem and phloem, respectively, involving Pi itself, hormones, miRNAs, mRNAs, and sucrose, serve to coordinate Pi deficiency responses at the whole-plant level. A combination of chromatin remodeling, transcriptional and posttranslational events contribute to globally regulating a wide range of Pi deficiency responses. In this review, recent advances are evaluated in terms of progress toward developing a comprehensive understanding of the molecular events underlying control over P homeostasis. Application of this knowledge, in terms of developing crop plants having enhanced attributes for P use efficiency, is discussed from the perspective of agricultural sustainability in the face of diminishing global P supplies. © 2014 Institute of Botany, Chinese Academy of Sciences.

Event Rate for LISA Gravitational Wave Signals from Black Hole-Massive Black Hole Coalescences

NASA Technical Reports Server (NTRS)

Bender, Peter L.

2002-01-01

Earlier work under a previous grant had been mainly on investigating the event rate for coalescences of white dwarfs or neutron stars with massive black holes (MBHs) in galactic nuclei. Under the new grant, two studies were undertaken. One was an approximate extension of the earlier study to stellar mass black holes as the lighter object, with masses in the range of roughly 3 to 20 solar mass rather than about 1 solar mass. The other was an improved estimate of the confusion noise due to galactic binaries against which the signals from BH-MBH coalescences would have to be detected. In the earlier work, the mass of the white dwarfs (WDs) and neutron stars (NSs) was assumed to be about the same as that of the evolved stars in the density cusp around the galactic center MBH. However, with the BH mass being substantially larger, the sinking down of pHs toward the center (mass segregation) became important, and was included in the model. A single representative mass of 7 solar mass was used. The other main difference involved what happened after the compact object got scattered in close enough to the MBH to start losing appreciable energy and angular momentum by gravitational radiation. For WDs or NSs, it had been found in most cases that the object would be perturbed considerably by other stars in the cusp before much energy had been lost. Thus the angular momentum would either increase enough so that gravitational radiation would be cut off, or would decrease enough so that the WD or NS would plunge into the MBH in just a few revolutions. The latter event would mean that the signal-to noise ratio would not have time to build up, and the event would not be detectable. The ratio of gradual energy loss events to plunges was found to be roughly one to a few percent, and thus substantially decreased the expected rate of detectable events.

? PID output-feedback control under event-triggered protocol

NASA Astrophysics Data System (ADS)

Zhao, Di; Wang, Zidong; Ding, Derui; Wei, Guoliang; Alsaadi, Fuad E.

2018-07-01

This paper is concerned with the ? proportional-integral-derivative (PID) output-feedback control problem for a class of linear discrete-time systems under event-triggered protocols. The controller and the actuators are connected through a communication network of limited bandwidth, and an event-triggered communication mechanism is adopted to decide when a certain control signal should be transmitted to the respective actuator. Furthermore, a novel PID output-feedback controller is designed where the accumulative sum-loop (the counterpart to the integral-loop in the continues-time setting) operates on a limited time-window with hope to mitigate the effect from the past measurement data. The main objective of the problem under consideration is to design a desired PID controller such that the closed-loop system is exponentially stable and the prescribed ? disturbance rejection attenuation level is guaranteed under event-triggered protocols. By means of the Lyapunov stability theory combined with the orthogonal decomposition, sufficient conditions are established under which the addressed PID controller design problem is recast into a linear convex optimization one that can be easily solved via available software packages. Finally, a simulation example is exploited to illustrate the usefulness and effectiveness of the established control scheme.

A class of temporal boundaries derived by quantifying the sense of separation.

PubMed

Paine, Llewyn Elise; Gilden, David L

2013-12-01

The perception of moment-to-moment environmental flux as being composed of meaningful events requires that memory processes coordinate with cues that signify beginnings and endings. We have constructed a technique that allows this coordination to be monitored indirectly. This technique works by embedding a sequential priming task into the event under study. Memory and perception must be coordinated to resolve temporal flux into scenes. The implicit memory processes inherent in sequential priming are able to effectively shadow then mirror scene-forming processes. Certain temporal boundaries are found to weaken the strength of irrelevant feature priming, a signal which can then be used in more ambiguous cases to infer how people segment time. Over the course of 13 independent studies, we were able to calibrate the technique and then use it to measure the strength of event segmentation in several instructive contexts that involved both visual and auditory modalities. The signal generated by sequential priming may permit the sense of separation between events to be measured as an extensive psychophysical quantity.

Coping with Trial-to-Trial Variability of Event Related Signals: A Bayesian Inference Approach

NASA Technical Reports Server (NTRS)

Ding, Mingzhou; Chen, Youghong; Knuth, Kevin H.; Bressler, Steven L.; Schroeder, Charles E.

2005-01-01

In electro-neurophysiology, single-trial brain responses to a sensory stimulus or a motor act are commonly assumed to result from the linear superposition of a stereotypic event-related signal (e.g. the event-related potential or ERP) that is invariant across trials and some ongoing brain activity often referred to as noise. To extract the signal, one performs an ensemble average of the brain responses over many identical trials to attenuate the noise. To date, h s simple signal-plus-noise (SPN) model has been the dominant approach in cognitive neuroscience. Mounting empirical evidence has shown that the assumptions underlying this model may be overly simplistic. More realistic models have been proposed that account for the trial-to-trial variability of the event-related signal as well as the possibility of multiple differentially varying components within a given ERP waveform. The variable-signal-plus-noise (VSPN) model, which has been demonstrated to provide the foundation for separation and characterization of multiple differentially varying components, has the potential to provide a rich source of information for questions related to neural functions that complement the SPN model. Thus, being able to estimate the amplitude and latency of each ERP component on a trial-by-trial basis provides a critical link between the perceived benefits of the VSPN model and its many concrete applications. In this paper we describe a Bayesian approach to deal with this issue and the resulting strategy is referred to as the differentially Variable Component Analysis (dVCA). We compare the performance of dVCA on simulated data with Independent Component Analysis (ICA) and analyze neurobiological recordings from monkeys performing cognitive tasks.

Method and apparatus for efficiently tracking queue entries relative to a timestamp

DOEpatents

Blumrich, Matthias A.; Chen, Dong; Gara, Alan G.; Giampapa, Mark E.; Heidelberger, Philip; Ohmacht, Martin; Salapura, Velentina; Vranas, Pavlos

2014-06-17

An apparatus and method for tracking coherence event signals transmitted in a multiprocessor system. The apparatus comprises a coherence logic unit, each unit having a plurality of queue structures with each queue structure associated with a respective sender of event signals transmitted in the system. A timing circuit associated with a queue structure controls enqueuing and dequeuing of received coherence event signals, and, a counter tracks a number of coherence event signals remaining enqueued in the queue structure and dequeued since receipt of a timestamp signal. A counter mechanism generates an output signal indicating that all of the coherence event signals present in the queue structure at the time of receipt of the timestamp signal have been dequeued. In one embodiment, the timestamp signal is asserted at the start of a memory synchronization operation and, the output signal indicates that all coherence events present when the timestamp signal was asserted have completed. This signal can then be used as part of the completion condition for the memory synchronization operation.

Seismic Characterization of the Newberry and Cooper Basin EGS Sites

NASA Astrophysics Data System (ADS)

Templeton, D. C.; Wang, J.; Goebel, M.; Johannesson, G.; Myers, S. C.; Harris, D.; Cladouhos, T. T.

2015-12-01

To aid in the seismic characterization of Engineered Geothermal Systems (EGS), we enhance traditional microearthquake detection and location methodologies at two EGS systems: the Newberry EGS site and the Habanero EGS site in the Cooper Basin of South Australia. We apply the Matched Field Processing (MFP) seismic imaging technique to detect new seismic events using known discrete microearthquake sources. Events identified using MFP typically have smaller magnitudes or occur within the coda of a larger event. Additionally, we apply a Bayesian multiple-event location algorithm, called MicroBayesLoc, to estimate the 95% probability ellipsoids for events with high signal-to-noise ratios (SNR). Such probability ellipsoid information can provide evidence for determining if a seismic lineation is real, or simply within the anticipated error range. At the Newberry EGS site, 235 events were reported in the original catalog. MFP identified 164 additional events (an increase of over 70% more events). For the relocated events in the Newberry catalog, we can distinguish two distinct seismic swarms that fall outside of one another's 95% probability error ellipsoids.This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Instrumentation for low noise nanopore-based ionic current recording under laser illumination

NASA Astrophysics Data System (ADS)

Roelen, Zachary; Bustamante, José A.; Carlsen, Autumn; Baker-Murray, Aidan; Tabard-Cossa, Vincent

2018-01-01

We describe a nanopore-based optofluidic instrument capable of performing low-noise ionic current recordings of individual biomolecules under laser illumination. In such systems, simultaneous optical measurements generally introduce significant parasitic noise in the electrical signal, which can severely reduce the instrument sensitivity, critically hindering the monitoring of single-molecule events in the ionic current traces. Here, we present design rules and describe simple adjustments to the experimental setup to mitigate the different noise sources encountered when integrating optical components to an electrical nanopore system. In particular, we address the contributions to the electrical noise spectra from illuminating the nanopore during ionic current recording and mitigate those effects through control of the illumination source and the use of a PDMS layer on the SiNx membrane. We demonstrate the effectiveness of our noise minimization strategies by showing the detection of DNA translocation events during membrane illumination with a signal-to-noise ratio of ˜10 at 10 kHz bandwidth. The instrumental guidelines for noise minimization that we report are applicable to a wide range of nanopore-based optofluidic systems and offer the possibility of enhancing the quality of synchronous optical and electrical signals obtained during single-molecule nanopore-based analysis.

Modeling of cell signaling pathways in macrophages by semantic networks

PubMed Central

Hsing, Michael; Bellenson, Joel L; Shankey, Conor; Cherkasov, Artem

2004-01-01

Background Substantial amounts of data on cell signaling, metabolic, gene regulatory and other biological pathways have been accumulated in literature and electronic databases. Conventionally, this information is stored in the form of pathway diagrams and can be characterized as highly "compartmental" (i.e. individual pathways are not connected into more general networks). Current approaches for representing pathways are limited in their capacity to model molecular interactions in their spatial and temporal context. Moreover, the critical knowledge of cause-effect relationships among signaling events is not reflected by most conventional approaches for manipulating pathways. Results We have applied a semantic network (SN) approach to develop and implement a model for cell signaling pathways. The semantic model has mapped biological concepts to a set of semantic agents and relationships, and characterized cell signaling events and their participants in the hierarchical and spatial context. In particular, the available information on the behaviors and interactions of the PI3K enzyme family has been integrated into the SN environment and a cell signaling network in human macrophages has been constructed. A SN-application has been developed to manipulate the locations and the states of molecules and to observe their actions under different biological scenarios. The approach allowed qualitative simulation of cell signaling events involving PI3Ks and identified pathways of molecular interactions that led to known cellular responses as well as other potential responses during bacterial invasions in macrophages. Conclusions We concluded from our results that the semantic network is an effective method to model cell signaling pathways. The semantic model allows proper representation and integration of information on biological structures and their interactions at different levels. The reconstruction of the cell signaling network in the macrophage allowed detailed investigation of connections among various essential molecules and reflected the cause-effect relationships among signaling events. The simulation demonstrated the dynamics of the semantic network, where a change of states on a molecule can alter its function and potentially cause a chain-reaction effect in the system. PMID:15494071

Virtual Seismometers for Induced Seismicity Monitoring and Full Moment Tensor Inversion

NASA Astrophysics Data System (ADS)

Morency, C.; Matzel, E.

2016-12-01

Induced seismicity is associated with subsurface fluid injection, and puts at risk efforts to develop geologic carbon sequestration and enhanced geothermal systems. We are developing methods to monitor the microseismically active zone so that we can ultimately identify faults at risk of slipping. The virtual seismometer method (VSM) is an interferometric technique that is very sensitive to the source parameters (location, mechanism and magnitude) and to the Earth structure in the source region. VSM works by virtually placing seismometers inside a micro events cloud, where we can focus on properties directly between induced micro events, and effectively replacing each earthquake with a virtual seismometer recording all the others. Here, we show that the cross-correlated signals from seismic wavefields triggered by two events and recorded at the surface are a combination of the strain field between these two sources times a moment tensor. Based on this relationship, we demonstrate how we can use these measured cross-correlated signals to invert for full moment tensor. The advantage of VSM is to allow to considerably reduce the modeled numerical domain to the region directly around the micro events cloud, which lowers computational cost, permits to reach higher frequency resolution, and suppresses the impact of the Earth structural model uncertainties outside the micro events cloud. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Automated Sensor Tuning for Seismic Event Detection at a Carbon Capture, Utilization, and Storage Site, Farnsworth Unit, Ochiltree County, Texas

NASA Astrophysics Data System (ADS)

Ziegler, A.; Balch, R. S.; Knox, H. A.; Van Wijk, J. W.; Draelos, T.; Peterson, M. G.

2016-12-01

We present results (e.g. seismic detections and STA/LTA detection parameters) from a continuous downhole seismic array in the Farnsworth Field, an oil field in Northern Texas that hosts an ongoing carbon capture, utilization, and storage project. Specifically, we evaluate data from a passive vertical monitoring array consisting of 16 levels of 3-component 15Hz geophones installed in the field and continuously recording since January 2014. This detection database is directly compared to ancillary data (i.e. wellbore pressure) to determine if there is any relationship between seismic observables and CO2 injection and pressure maintenance in the field. Of particular interest is detection of relatively low-amplitude signals constituting long-period long-duration (LPLD) events that may be associated with slow shear-slip analogous to low frequency tectonic tremor. While this category of seismic event provides great insight into dynamic behavior of the pressurized subsurface, it is inherently difficult to detect. To automatically detect seismic events using effective data processing parameters, an automated sensor tuning (AST) algorithm developed by Sandia National Laboratories is being utilized. AST exploits ideas from neuro-dynamic programming (reinforcement learning) to automatically self-tune and determine optimal detection parameter settings. AST adapts in near real-time to changing conditions and automatically self-tune a signal detector to identify (detect) only signals from events of interest, leading to a reduction in the number of missed legitimate event detections and the number of false event detections. Funding for this project is provided by the U.S. Department of Energy's (DOE) National Energy Technology Laboratory (NETL) through the Southwest Regional Partnership on Carbon Sequestration (SWP) under Award No. DE-FC26-05NT42591. Additional support has been provided by site operator Chaparral Energy, L.L.C. and Schlumberger Carbon Services. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Acoustic emission from trabecular bone during mechanical testing: the effect of osteoporosis and osteoarthritis.

PubMed

Leichter, I; Bivas, A; Margulies, J Y; Roman, I; Simkin, A

1990-01-01

This study examines the relation between the nature of acoustic emission signals emitted from cancellous bone under compression and the mechanical properties of the tissue. The examined bone specimens were taken from 12 normal, 31 osteoporotic and six osteoarthritic femoral heads. The mechanical behaviour of the osteoporotic bone specimens was found to be significantly different from that of the normal specimens both in the pre-yield and post-yield ranges. In the osteoarthritic bones only the elastic behaviour was significantly different. The rates of acoustic events before yield and beyond it were found to be significantly higher both in the osteoporotic and osteoarthritic bone specimens. The average peak amplitude of the signals was also significantly higher in the diseased bones. Stepwise regression analysis showed that a combination of the acoustic emission parameters could significantly predict some mechanical properties of the bone. The energy absorbed during compression and the ultimate compressive stress of the specimens could be estimated from the rate of pre-yield acoustic events, the average amplitude of the signals and the rate of post-yield events. However, the explanation power of the acoustic emission parameters was only moderate. The nature of acoustic emission signals was thus demonstrated to be a potential tool for assessing bone quality.

Early multisensory interactions affect the competition among multiple visual objects.

PubMed

Van der Burg, Erik; Talsma, Durk; Olivers, Christian N L; Hickey, Clayton; Theeuwes, Jan

2011-04-01

In dynamic cluttered environments, audition and vision may benefit from each other in determining what deserves further attention and what does not. We investigated the underlying neural mechanisms responsible for attentional guidance by audiovisual stimuli in such an environment. Event-related potentials (ERPs) were measured during visual search through dynamic displays consisting of line elements that randomly changed orientation. Search accuracy improved when a target orientation change was synchronized with an auditory signal as compared to when the auditory signal was absent or synchronized with a distractor orientation change. The ERP data show that behavioral benefits were related to an early multisensory interaction over left parieto-occipital cortex (50-60 ms post-stimulus onset), which was followed by an early positive modulation (80-100 ms) over occipital and temporal areas contralateral to the audiovisual event, an enhanced N2pc (210-250 ms), and a contralateral negative slow wave (CNSW). The early multisensory interaction was correlated with behavioral search benefits, indicating that participants with a strong multisensory interaction benefited the most from the synchronized auditory signal. We suggest that an auditory signal enhances the neural response to a synchronized visual event, which increases the chances of selection in a multiple object environment. Copyright © 2010 Elsevier Inc. All rights reserved.

Transcriptomic analyses and leukocyte telomere length measurement in subjects exposed to severe recent stressful life events.

PubMed

Lopizzo, N; Tosato, S; Begni, V; Tomassi, S; Cattane, N; Barcella, M; Turco, G; Ruggeri, M; Riva, M A; Pariante, C M; Cattaneo, A

2017-02-21

Stressful life events occurring in adulthood have been found able to affect mood and behavior, thus increasing the vulnerability for several stress-related psychiatric disorders. However, although there is plenty of clinical data supporting an association between stressful life events in adulthood and an enhanced vulnerability for psychopathology, the underlying molecular mechanisms are still poorly investigated. Thus, in this study we performed peripheral/whole-genome transcriptomic analyses in blood samples obtained from 53 adult subjects characterized for recent stressful life events occurred within the previous 6 months. Transcriptomic data were analyzed using Partek Genomics Suite; pathway and network analyses were performed using Ingenuity Pathway Analysis and GeneMANIA Software. We found 207 genes significantly differentially expressed in adult subjects who reported recent stressful life experiences (n=21) compared with those without such experiences (n=32). Moreover, the same subjects exposed to such stressful experiences showed a reduction in leukocyte telomere length. A correlation analyses between telomere length and transcriptomic data indicated an association between the exposures to recent stressful life events and the modulation of several pathways, mainly involved in immune-inflammatory-related processes and oxidative stress, such as natural killer cell signaling, interleukin-1 (IL-1) signaling, MIF regulation of innate immunity and IL-6 signaling. Our data suggest an association between exposures to recent stressful life events in adulthood and alterations in the immune, inflammatory and oxidative stress pathways, which could be also involved in the negative effect of stressful life events on leukocyte telomere length. The modulation of these mechanisms may underlie the clinical association between the exposure to recent Stressful life events in adulthood and an enhanced vulnerability to develop psychiatric diseases in adulthood.

Multiple Transient Signals in Human Visual Cortex Associated with an Elementary Decision

PubMed Central

Nolte, Guido

2017-01-01

The cerebral cortex continuously undergoes changes in its state, which are manifested in transient modulations of the cortical power spectrum. Cortical state changes also occur at full wakefulness and during rapid cognitive acts, such as perceptual decisions. Previous studies found a global modulation of beta-band (12–30 Hz) activity in human and monkey visual cortex during an elementary visual decision: reporting the appearance or disappearance of salient visual targets surrounded by a distractor. The previous studies disentangled neither the motor action associated with behavioral report nor other secondary processes, such as arousal, from perceptual decision processing per se. Here, we used magnetoencephalography in humans to pinpoint the factors underlying the beta-band modulation. We found that disappearances of a salient target were associated with beta-band suppression, and target reappearances with beta-band enhancement. This was true for both overt behavioral reports (immediate button presses) and silent counting of the perceptual events. This finding indicates that the beta-band modulation was unrelated to the execution of the motor act associated with a behavioral report of the perceptual decision. Further, changes in pupil-linked arousal, fixational eye movements, or gamma-band responses were not necessary for the beta-band modulation. Together, our results suggest that the beta-band modulation was a top-down signal associated with the process of converting graded perceptual signals into a categorical format underlying flexible behavior. This signal may have been fed back from brain regions involved in decision processing to visual cortex, thus enforcing a “decision-consistent” cortical state. SIGNIFICANCE STATEMENT Elementary visual decisions are associated with a rapid state change in visual cortex, indexed by a modulation of neural activity in the beta-frequency range. Such decisions are also followed by other events that might affect the state of visual cortex, including the motor command associated with the report of the decision, an increase in pupil-linked arousal, fixational eye movements, and fluctuations in bottom-up sensory processing. Here, we ruled out the necessity of these events for the beta-band modulation of visual cortex. We propose that the modulation reflects a decision-related state change, which is induced by the conversion of graded perceptual signals into a categorical format underlying behavior. The resulting decision signal may be fed back to visual cortex. PMID:28495972

Constructing An Event Based Aerosol Product Under High Aerosol Loading Conditions

NASA Astrophysics Data System (ADS)

Levy, R. C.; Shi, Y.; Mattoo, S.; Remer, L. A.; Zhang, J.

2016-12-01

High aerosol loading events, such as the Indonesia's forest fire in Fall 2015 or the persistent wintertime haze near Beijing, gain tremendous interests due to their large impact on regional visibility and air quality. Understanding the optical properties of these events and further being able to simulate and predict these events are beneficial. However, it is a great challenge to consistently identify and then retrieve aerosol optical depth (AOD) from passive sensors during heavy aerosol events. Some reasons include:1). large differences between optical properties of high-loading aerosols and those under normal conditions, 2) spectral signals of optically thick aerosols can be mistaken with surface depending on aerosol types, and 3) Extremely optically thick aerosol plumes can also be misidentified as clouds due to its high optical thickness. Thus, even under clear-sky conditions, the global distribution of extreme aerosol events is not well captured in datasets such as the MODIS Dark-Target (DT) aerosol product. In this study, with the synthetic use of OMI Aerosol Index, MODIS cloud product, and operational DT product, the heavy smoke events over the seven sea region are identified and retrieved over the dry season. An event based aerosol product that would compensate the standard "global" aerosol retrieval will be created and evaluated. The impact of missing high AOD retrievals on the regional aerosol climatology will be studied using this newly developed research product.

Intercellular Variation in Signaling through the TGF-β Pathway and Its Relation to Cell Density and Cell Cycle Phase*

PubMed Central

Zieba, Agata; Pardali, Katerina; Söderberg, Ola; Lindbom, Lena; Nyström, Erik; Moustakas, Aristidis; Heldin, Carl-Henrik; Landegren, Ulf

2012-01-01

Fundamental open questions in signal transduction remain concerning the sequence and distribution of molecular signaling events among individual cells. In this work, we have characterized the intercellular variability of transforming growth factor β-induced Smad interactions, providing essential information about TGF-β signaling and its dependence on the density of cell populations and the cell cycle phase. By employing the recently developed in situ proximity ligation assay, we investigated the dynamics of interactions and modifications of Smad proteins and their partners under native and physiological conditions. We analyzed the kinetics of assembly of Smad complexes and the influence of cellular environment and relation to mitosis. We report rapid kinetics of formation of Smad complexes, including native Smad2-Smad3-Smad4 trimeric complexes, in a manner influenced by the rate of proteasomal degradation of these proteins, and we found a striking cell to cell variation of signaling complexes. The single-cell analysis of TGF-β signaling in genetically unmodified cells revealed previously unknown aspects of regulation of this pathway, and it provided a basis for analysis of these signaling events to diagnose pathological perturbations in patient samples and to evaluate their susceptibility to drug treatment. PMID:22442258

ELECTRONIC SYSTEM

DOEpatents

Robison, G.H. et al.

1960-11-15

An electronic system is described for indicating the occurrence of a plurality of electrically detectable events within predetermined time intervals. It is comprised of separate input means electrically associated with the events under observation: an electronic channel associated with each input means including control means and indicating means; timing means associated with each of the input means and the control means and adapted to derive a signal from the input means and apply it after a predetermined time to the control means to effect deactivation of each of the channels; and means for resetting the system to its initial condition after observation of each group of events.

Extreme event statistics in a drifting Markov chain

NASA Astrophysics Data System (ADS)

Kindermann, Farina; Hohmann, Michael; Lausch, Tobias; Mayer, Daniel; Schmidt, Felix; Widera, Artur

2017-07-01

We analyze extreme event statistics of experimentally realized Markov chains with various drifts. Our Markov chains are individual trajectories of a single atom diffusing in a one-dimensional periodic potential. Based on more than 500 individual atomic traces we verify the applicability of the Sparre Andersen theorem to our system despite the presence of a drift. We present detailed analysis of four different rare-event statistics for our system: the distributions of extreme values, of record values, of extreme value occurrence in the chain, and of the number of records in the chain. We observe that, for our data, the shape of the extreme event distributions is dominated by the underlying exponential distance distribution extracted from the atomic traces. Furthermore, we find that even small drifts influence the statistics of extreme events and record values, which is supported by numerical simulations, and we identify cases in which the drift can be determined without information about the underlying random variable distributions. Our results facilitate the use of extreme event statistics as a signal for small drifts in correlated trajectories.

Effects of shifts in the rate of repetitive stimulation on sustained attention

NASA Technical Reports Server (NTRS)

Krulewitz, J. E.; Warm, J. S.; Wohl, T. H.

1975-01-01

The effects of shifts in the rate of presentation of repetitive neutral events (background event rate) were studied in a visual vigilance task. Four groups of subjects experienced either a high (21 events/min) or a low (6 events/min) event rate for 20 min and then experienced either the same or the alternate event rate for an additional 40 min. The temporal occurrence of critical target signals was identical for all groups, irrespective of event rate. The density of critical signals was 12 signals/20 min. By the end of the session, shifts in event rate were associated with changes in performance which resembled contrast effects found in other experimental situations in which shift paradigms were used. Relative to constant event rate control conditions, a shift from a low to a high event rate depressed the probability of signal detections, while a shift in the opposite direction enhanced the probability of signal detections.

Propagation of Flexural Mode AE Signals in GR/EP Composite Plates

NASA Technical Reports Server (NTRS)

Prosser, W. H.; Gorman, M. R.

1992-01-01

It has been documented that AE signals propagate in thin plates as extensional and flexural plate modes. This was demonstrated using simulated AE sources (pencil lead breaks) by Gorman on thin aluminum and gr/ep composite plates and by Gorman and Prosser on thin aluminum plates. A typical signal from a pencil lead break source which identifies these two modes is shown. AE signals from transverse matrix cracking sources in gr/ep composite plates were also shown to propagate as plate modes by Gorman and Ziola. Smith showed that crack growth events in thin aluminum plates under spectrum fatigue loading produced signals that propagated as plate modes. Additionally, Prosser et al. showed that AE signals propagated as plate modes in a thin walled composite tube.

Neural dynamics of reward probability coding: a Magnetoencephalographic study in humans

PubMed Central

Thomas, Julie; Vanni-Mercier, Giovanna; Dreher, Jean-Claude

2013-01-01

Prediction of future rewards and discrepancy between actual and expected outcomes (prediction error) are crucial signals for adaptive behavior. In humans, a number of fMRI studies demonstrated that reward probability modulates these two signals in a large brain network. Yet, the spatio-temporal dynamics underlying the neural coding of reward probability remains unknown. Here, using magnetoencephalography, we investigated the neural dynamics of prediction and reward prediction error computations while subjects learned to associate cues of slot machines with monetary rewards with different probabilities. We showed that event-related magnetic fields (ERFs) arising from the visual cortex coded the expected reward value 155 ms after the cue, demonstrating that reward value signals emerge early in the visual stream. Moreover, a prediction error was reflected in ERF peaking 300 ms after the rewarded outcome and showing decreasing amplitude with higher reward probability. This prediction error signal was generated in a network including the anterior and posterior cingulate cortex. These findings pinpoint the spatio-temporal characteristics underlying reward probability coding. Together, our results provide insights into the neural dynamics underlying the ability to learn probabilistic stimuli-reward contingencies. PMID:24302894

PSGMiner: A modular software for polysomnographic analysis.

PubMed

Umut, İlhan

2016-06-01

Sleep disorders affect a great percentage of the population. The diagnosis of these disorders is usually made by polysomnography. This paper details the development of new software to carry out feature extraction in order to perform robust analysis and classification of sleep events using polysomnographic data. The software, called PSGMiner, is a tool, which visualizes, processes and classifies bioelectrical data. The purpose of this program is to provide researchers with a platform with which to test new hypotheses by creating tests to check for correlations that are not available in commercially available software. The software is freely available under the GPL3 License. PSGMiner is composed of a number of diverse modules such as feature extraction, annotation, and machine learning modules, all of which are accessible from the main module. Using the software, it is possible to extract features of polysomnography using digital signal processing and statistical methods and to perform different analyses. The features can be classified through the use of five classification algorithms. PSGMiner offers an architecture designed for integrating new methods. Automatic scoring, which is available in almost all commercial PSG software, is not inherently available in this program, though it can be implemented by two different methodologies (machine learning and algorithms). While similar software focuses on a certain signal or event composed of a small number of modules with no expansion possibility, the software introduced here can handle all polysomnographic signals and events. The software simplifies the processing of polysomnographic signals for researchers and physicians that are not experts in computer programming. It can find correlations between different events which could help predict an oncoming event such as sleep apnea. The software could also be used for educational purposes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Safety of herbal products in Thailand: an analysis of reports in the thai health product vigilance center database from 2000 to 2008.

PubMed

Saokaew, Surasak; Suwankesawong, Wimon; Permsuwan, Unchalee; Chaiyakunapruk, Nathorn

2011-04-01

The use of herbal products continues to expand rapidly across the world and concerns regarding the safety of these products have been raised. In Thailand, Thai Vigibase, developed by the Health Product Vigilance Center (HPVC) under the Thai Food and Drug Administration, is the national database that collates reports from health product surveillance systems and programmes. Thai Vigibase can be used to identify signals of adverse events in patients receiving herbal products. The purpose of the study was to describe the characteristics of reported adverse events in patients receiving herbal products in Thailand. Thai Vigibase data from February 2000 to December 2008 involving adverse events reported in association with herbal products were used. This database includes case reports submitted through the spontaneous reporting system and intensive monitoring programmes. Under the spontaneous reporting system, adverse event reports are collected nationwide via a national network of 22 regional centres covering more than 800 public and private hospitals, and health service centres. An intensive monitoring programme was also conducted to monitor the five single herbal products listed in the Thai National List of Essential Medicines (NLEM), while another intensive monitoring programme was developed to monitor the four single herbal products that were under consideration for inclusion in the NLEM. The database contained patient demographics, adverse events associated with herbal products, and details on seriousness, causality and quality of reports. Descriptive statistics were used for data analyses. A total of 593 reports with 1868 adverse events involving 24 different products were made during the study period. The age range of individuals was 1-86 years (mean 47 years). Most case reports were obtained from the intensive monitoring programme. Of the reports, 72% involved females. The herbal products for which adverse events were frequently reported were products containing turmeric (44%), followed by andrographis (10%), veld grape (10%), pennywort (7%), plai (6%), jewel vine (6%), bitter melon (5%) and snake plant (5%). Gastrointestinal problems were the most common adverse effect reported. Serious adverse events included Stevens-Johnson syndrome, anaphylactic shock and exfoliative dermatitis. Adverse event reports on herbals products were diverse, with most of them being reported through intensive monitoring programmes. Thai Vigibase is a potentially effective data source for signal detection of adverse events associated with herbal products.

Wavelet entropy: a new tool for analysis of short duration brain electrical signals.

PubMed

Rosso, O A; Blanco, S; Yordanova, J; Kolev, V; Figliola, A; Schürmann, M; Başar, E

2001-01-30

Since traditional electrical brain signal analysis is mostly qualitative, the development of new quantitative methods is crucial for restricting the subjectivity in the study of brain signals. These methods are particularly fruitful when they are strongly correlated with intuitive physical concepts that allow a better understanding of brain dynamics. Here, new method based on orthogonal discrete wavelet transform (ODWT) is applied. It takes as a basic element the ODWT of the EEG signal, and defines the relative wavelet energy, the wavelet entropy (WE) and the relative wavelet entropy (RWE). The relative wavelet energy provides information about the relative energy associated with different frequency bands present in the EEG and their corresponding degree of importance. The WE carries information about the degree of order/disorder associated with a multi-frequency signal response, and the RWE measures the degree of similarity between different segments of the signal. In addition, the time evolution of the WE is calculated to give information about the dynamics in the EEG records. Within this framework, the major objective of the present work was to characterize in a quantitative way functional dynamics of order/disorder microstates in short duration EEG signals. For that aim, spontaneous EEG signals under different physiological conditions were analyzed. Further, specific quantifiers were derived to characterize how stimulus affects electrical events in terms of frequency synchronization (tuning) in the event related potentials.

Early/fast VLF events produced by the quiescent heating of the lower ionosphere by thunderstorms

NASA Astrophysics Data System (ADS)

Kabirzadeh, R.; Marshall, R. A.; Inan, U. S.

2017-06-01

Large and easily distinguishable perturbations of the VLF transmitter signals due to interactions with thundercloud-driven ionospheric modifications have been observed and studied for about three decades. These events are called "early/fast VLF" or "early VLF" events due to their immediate detection (˜20 ms) after the causative lightning flash on the ground and the fast rise time of the perturbed signal. Despite many years of study, the physical mechanisms responsible for these perturbations are still under investigation. Modifications of the sustained heating level of the ionosphere due to a lightning flash has been previously proposed as the causative mechanism of early/fast VLF events. The perturbations predicted by this mechanism, however, have been much smaller than experimental observations of 0.2-1 dB or higher. In this study, by using an improved 3-D thundercloud electrostatic upward coupling model which uses a realistic geomagnetic field, we find that the sustained heating model can predict perturbations that are consistent with reported experimental observations. Modifications in the quiescent heating of the lower ionosphere by thundercloud fields by individual lightning flashes may thus account for some observations of early/fast VLF events.

Transcriptome profiles of embryos before and after cleavage in Eriocheir sinensis: identification of developmental genes at the earliest stages

NASA Astrophysics Data System (ADS)

Hui, Min; Cui, Zhaoxia; Liu, Yuan; Song, Chengwen

2017-07-01

In crab, embryogenesis is a complicated developmental program marked by a series of critical events. RNA-Sequencing technology offers developmental biologists a way to identify many more developmental genes than ever before. Here, we present a comprehensive analysis of the transcriptomes of Eriocheir sinensis oosperms (Os) and embryos at the 2-4 cell stage (Cs), which are separated by a cleavage event. A total of 18 923 unigenes were identified, and 403 genes matched with gene ontology (GO) terms related to developmental processes. In total, 432 differentially expressed genes (DEGs) were detected between the two stages. Nine DEGs were specifically expressed at only one stage. These DEGs may be relevant to stage-specific molecular events during development. A number of DEGs related to `hedgehog signaling pathway', `Wnt signaling pathway' `germplasm', `nervous system', `sensory perception' and `segment polarity' were identified as being up-regulated at the Cs stage. The results suggest that these embryonic developmental events begin before the early cleavage event in crabs, and that many of the genes expressed in the two transcriptomes might be maternal genes. Our study provides ample information for further research on the molecular mechanisms underlying crab development.

Signaling events during initiation of arbuscular mycorrhizal symbiosis.

PubMed

Schmitz, Alexa M; Harrison, Maria J

2014-03-01

Under nutrient-limiting conditions, plants will enter into symbiosis with arbuscular mycorrhizal (AM) fungi for the enhancement of mineral nutrient acquisition from the surrounding soil. AM fungi live in close, intracellular association with plant roots where they transfer phosphate and nitrogen to the plant in exchange for carbon. They are obligate fungi, relying on their host as their only carbon source. Much has been discovered in the last decade concerning the signaling events during initiation of the AM symbiosis, including the identification of signaling molecules generated by both partners. This signaling occurs through symbiosis-specific gene products in the host plant, which are indispensable for normal AM development. At the same time, plants have adapted complex mechanisms for avoiding infection by pathogenic fungi, including an innate immune response to general microbial molecules, such as chitin present in fungal cell walls. How it is that AM fungal colonization is maintained without eliciting a defensive response from the host is still uncertain. In this review, we present a summary of the molecular signals and their elicited responses during initiation of the AM symbiosis, including plant immune responses and their suppression. © 2014 Institute of Botany, Chinese Academy of Sciences.

Paraesthesia after local anaesthetics: an analysis of reports to the FDA Adverse Event Reporting System.

PubMed

Piccinni, Carlo; Gissi, Davide B; Gabusi, Andrea; Montebugnoli, Lucio; Poluzzi, Elisabetta

2015-07-01

This study was aimed to evaluate the possible alert signals of paraesthesia by local anaesthetics, focusing on those used in dentistry. A case/non-case study of spontaneous adverse events recorded in FAERS (FDA Adverse Event Reporting System) between 2004 and 2011 was performed. Cases were represented by the reports of reactions grouped under the term 'Paraesthesias and dysaesthesias' involving local anaesthetics (ATC: N01B*); non-cases were all other reports of the same drugs. Reporting odds ratios (ROR) with the relevant 95% confidence intervals (95CI) were calculated. Alert signal was considered when number of cases >3 and lower limit of ROR 95CI > 1. To estimate the specificity of signals for dentistry, the analysis was restricted to the specific term "Oral Paraesthesia" and to reports concerning dental practice. Overall, 528 reports of 'Paraesthesias and dysaesthesias' were retrieved, corresponding to 573 drug-reaction pairs (247 lidocaine, 99 bupivacaine, 85 articaine, 30 prilocaine, 112 others). The signal was significant only for articaine (ROR=18.38; 95CI = 13.95-24.21) and prilocaine (2.66; 1.82-3.90). The analysis of the specific term "Oral Paraesthesia" retrieved 82 reports corresponding to 90 drug-reaction pairs (37 articaine, 19 lidocaine, 14 prilocaine, 7 bupivacaine, 13 others) and confirmed the signal for articaine (58.77; 37.82-91.31) and prilocaine (8.73; 4.89-15.57). The analysis of reports concerning dental procedures retrieved a signal for articaine, both for any procedures (8.84; 2.79-27.97) and for non-surgical ones (15.79; 1.87-133.46). In conclusion, among local anaesthetics, only articaine and prilocaine generated a signal of paraesthesia, especially when used in dentistry. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Molecular Programs Underlying Asymmetric Stem Cell Division and Their Disruption in Malignancy.

PubMed

Mukherjee, Subhas; Brat, Daniel J

2017-01-01

Asymmetric division of stem cells is a highly conserved and tightly regulated process by which a single stem cell produces two unequal daughter cells. One retains its stem cell identity while the other becomes specialized through a differentiation program and loses stem cell properties. Coordinating these events requires control over numerous intra- and extracellular biological processes and signaling networks. In the initial stages, critical events include the compartmentalization of fate determining proteins within the mother cell and their subsequent passage to the appropriate daughter cell in order to direct their destiny. Disturbance of these events results in an altered dynamic of self-renewing and differentiation within the cell population, which is highly relevant to the growth and progression of cancer. Other critical events include proper asymmetric spindle assembly, extrinsic regulation through micro-environmental cues, and non-canonical signaling networks that impact cell division and fate determination. In this review, we discuss mechanisms that maintain the delicate balance of asymmetric cell division in normal tissues and describe the current understanding how some of these mechanisms are deregulated in cancer.

Search for a standard model Higgs boson produced in association with a top-quark pair and decaying to bottom quarks using a matrix element method

NASA Astrophysics Data System (ADS)

Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Bergauer, T.; Dragicevic, M.; Erö, J.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hartl, C.; Hörmann, N.; Hrubec, J.; Jeitler, M.; Kiesenhofer, W.; Knünz, V.; Krammer, M.; Krätschmer, I.; Liko, D.; Mikulec, I.; Rabady, D.; Rahbaran, B.; Rohringer, H.; Schöfbeck, R.; Strauss, J.; Treberer-Treberspurg, W.; Waltenberger, W.; Wulz, C.-E.; Mossolov, V.; Shumeiko, N.; Suarez Gonzalez, J.; Alderweireldt, S.; Bansal, S.; Cornelis, T.; De Wolf, E. A.; Janssen, X.; Knutsson, A.; Lauwers, J.; Luyckx, S.; Ochesanu, S.; Rougny, R.; Van De Klundert, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Blekman, F.; Blyweert, S.; D'Hondt, J.; Daci, N.; Heracleous, N.; Keaveney, J.; Lowette, S.; Maes, M.; Olbrechts, A.; Python, Q.; Strom, D.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Onsem, G. P.; Villella, I.; Caillol, C.; Clerbaux, B.; De Lentdecker, G.; Dobur, D.; Favart, L.; Gay, A. P. R.; Grebenyuk, A.; Léonard, A.; Mohammadi, A.; Perniè, L.; Randle-conde, A.; Reis, T.; Seva, T.; Thomas, L.; Vander Velde, C.; Vanlaer, P.; Wang, J.; Zenoni, F.; Adler, V.; Beernaert, K.; Benucci, L.; Cimmino, A.; Costantini, S.; Crucy, S.; Fagot, A.; Garcia, G.; Mccartin, J.; Ocampo Rios, A. A.; Poyraz, D.; Ryckbosch, D.; Salva Diblen, S.; Sigamani, M.; Strobbe, N.; Thyssen, F.; Tytgat, M.; Yazgan, E.; Zaganidis, N.; Basegmez, S.; Beluffi, C.; Bruno, G.; Castello, R.; Caudron, A.; Ceard, L.; Da Silveira, G. G.; Delaere, C.; du Pree, T.; Favart, D.; Forthomme, L.; Giammanco, A.; Hollar, J.; Jafari, A.; Jez, P.; Komm, M.; Lemaitre, V.; Nuttens, C.; Pagano, D.; Perrini, L.; Pin, A.; Piotrzkowski, K.; Popov, A.; Quertenmont, L.; Selvaggi, M.; Vidal Marono, M.; Vizan Garcia, J. M.; Beliy, N.; Caebergs, T.; Daubie, E.; Hammad, G. H.; Júnior, W. L. Aldá; Alves, G. A.; Brito, L.; Correa Martins Junior, M.; Martins, T. Dos Reis; Molina, J.; Mora Herrera, C.; Pol, M. E.; Rebello Teles, P.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; De Jesus Damiao, D.; De Oliveira Martins, C.; Fonseca De Souza, S.; Malbouisson, H.; Matos Figueiredo, D.; Mundim, L.; Nogima, H.; Prado Da Silva, W. L.; Santaolalla, J.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Vilela Pereira, A.; Bernardes, C. A.; Dogra, S.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Aleksandrov, A.; Genchev, V.; Hadjiiska, R.; Iaydjiev, P.; Marinov, A.; Piperov, S.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Vutova, M.; Dimitrov, A.; Glushkov, I.; Litov, L.; Pavlov, B.; Petkov, P.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Cheng, T.; Du, R.; Jiang, C. H.; Plestina, R.; Romeo, F.; Tao, J.; Wang, Z.; Asawatangtrakuldee, C.; Ban, Y.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Xu, Z.; Zhang, F.; Zhang, L.; Zou, W.; Avila, C.; Cabrera, A.; Chaparro Sierra, L. F.; Florez, C.; Gomez, J. P.; Gomez Moreno, B.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Polic, D.; Puljak, I.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Kadija, K.; Luetic, J.; Mekterovic, D.; Sudic, L.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Bodlak, M.; Finger, M.; Finger, M.; Assran, Y.; Ellithi Kamel, A.; Mahmoud, M. A.; Radi, A.; Kadastik, M.; Murumaa, M.; Raidal, M.; Tiko, A.; Eerola, P.; Voutilainen, M.; Härkönen, J.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Peltola, T.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Wendland, L.; Talvitie, J.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Fabbro, B.; Faure, J. L.; Favaro, C.; Ferri, F.; Ganjour, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Locci, E.; Malcles, J.; Rander, J.; Rosowsky, A.; Titov, M.; Baffioni, S.; Beaudette, F.; Busson, P.; Chapon, E.; Charlot, C.; Dahms, T.; Dobrzynski, L.; Filipovic, N.; Florent, A.; Granier de Cassagnac, R.; Mastrolorenzo, L.; Miné, P.; Naranjo, I. N.; Nguyen, M.; Ochando, C.; Ortona, G.; Paganini, P.; Regnard, S.; Salerno, R.; Sauvan, J. B.; Sirois, Y.; Veelken, C.; Yilmaz, Y.; Zabi, A.; Agram, J.-L.; Andrea, J.; Aubin, A.; Bloch, D.; Brom, J.-M.; Chabert, E. C.; Chanon, N.; Collard, C.; Conte, E.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Goetzmann, C.; Le Bihan, A.-C.; Skovpen, K.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Beaupere, N.; Bernet, C.; Boudoul, G.; Bouvier, E.; Brochet, S.; Carrillo Montoya, C. A.; Chasserat, J.; Chierici, R.; Contardo, D.; Courbon, B.; Depasse, P.; El Mamouni, H.; Fan, J.; Fay, J.; Gascon, S.; Gouzevitch, M.; Ille, B.; Kurca, T.; Lethuillier, M.; Mirabito, L.; Pequegnot, A. L.; Perries, S.; Ruiz Alvarez, J. D.; Sabes, D.; Sgandurra, L.; Sordini, V.; Vander Donckt, M.; Verdier, P.; Viret, S.; Xiao, H.; Tsamalaidze, Z.; Autermann, C.; Beranek, S.; Bontenackels, M.; Edelhoff, M.; Feld, L.; Heister, A.; Klein, K.; Lipinski, M.; Ostapchuk, A.; Preuten, M.; Raupach, F.; Sammet, J.; Schael, S.; Schulte, J. F.; Weber, H.; Wittmer, B.; Zhukov, V.; Ata, M.; Brodski, M.; Dietz-Laursonn, E.; Duchardt, D.; Erdmann, M.; Fischer, R.; Güth, A.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Klingebiel, D.; Knutzen, S.; Kreuzer, P.; Merschmeyer, M.; Meyer, A.; Mittag, G.; Millet, P.; Olschewski, M.; Padeken, K.; Papacz, P.; Reithler, H.; Schmitz, S. A.; Sonnenschein, L.; Teyssier, D.; Thüer, S.; Cherepanov, V.; Erdogan, Y.; Flügge, G.; Geenen, H.; Geisler, M.; Haj Ahmad, W.; Hoehle, F.; Kargoll, B.; Kress, T.; Kuessel, Y.; Künsken, A.; Lingemann, J.; Nowack, A.; Nugent, I. M.; Pistone, C.; Pooth, O.; Stahl, A.; Aldaya Martin, M.; Asin, I.; Bartosik, N.; Behr, J.; Behrens, U.; Bell, A. J.; Bethani, A.; Borras, K.; Burgmeier, A.; Cakir, A.; Calligaris, L.; Campbell, A.; Choudhury, S.; Costanza, F.; Diez Pardos, C.; Dolinska, G.; Dooling, S.; Dorland, T.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Flucke, G.; Garcia, J. Garay; Geiser, A.; Gizhko, A.; Gunnellini, P.; Hauk, J.; Hempel, M.; Jung, H.; Kalogeropoulos, A.; Karacheban, O.; Kasemann, M.; Katsas, P.; Kieseler, J.; Kleinwort, C.; Korol, I.; Krücker, D.; Lange, W.; Leonard, J.; Lipka, K.; Lobanov, A.; Lohmann, W.; Lutz, B.; Mankel, R.; Marfin, I.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mnich, J.; Mussgiller, A.; Naumann-Emme, S.; Nayak, A.; Ntomari, E.; Perrey, H.; Pitzl, D.; Placakyte, R.; Raspereza, A.; Ribeiro Cipriano, P. M.; Roland, B.; Ron, E.; Sahin, M. Ö.; Salfeld-Nebgen, J.; Saxena, P.; Schoerner-Sadenius, T.; Schröder, M.; Seitz, C.; Spannagel, S.; Vargas Trevino, A. D. R.; Walsh, R.; Wissing, C.; Blobel, V.; Centis Vignali, M.; Draeger, A. R.; Erfle, J.; Garutti, E.; Goebel, K.; Görner, M.; Haller, J.; Hoffmann, M.; Höing, R. S.; Junkes, A.; Kirschenmann, H.; Klanner, R.; Kogler, R.; Lapsien, T.; Lenz, T.; Marchesini, I.; Marconi, D.; Nowatschin, D.; Ott, J.; Peiffer, T.; Perieanu, A.; Pietsch, N.; Poehlsen, J.; Poehlsen, T.; Rathjens, D.; Sander, C.; Schettler, H.; Schleper, P.; Schlieckau, E.; Schmidt, A.; Seidel, M.; Sola, V.; Stadie, H.; Steinbrück, G.; Troendle, D.; Usai, E.; Vanelderen, L.; Vanhoefer, A.; Akbiyik, M.; Barth, C.; Baus, C.; Berger, J.; Böser, C.; Butz, E.; Chwalek, T.; De Boer, W.; Descroix, A.; Dierlamm, A.; Feindt, M.; Frensch, F.; Giffels, M.; Gilbert, A.; Hartmann, F.; Hauth, T.; Husemann, U.; Katkov, I.; Kornmayer, A.; Lobelle Pardo, P.; Mozer, M. U.; Müller, T.; Müller, Th.; Nürnberg, A.; Quast, G.; Rabbertz, K.; Röcker, S.; Simonis, H. J.; Stober, F. M.; Ulrich, R.; Wagner-Kuhr, J.; Wayand, S.; Weiler, T.; Wöhrmann, C.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. A.; Kyriakis, A.; Loukas, D.; Markou, A.; Markou, C.; Psallidas, A.; Topsis-Giotis, I.; Agapitos, A.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Stiliaris, E.; Tziaferi, E.; Aslanoglou, X.; Evangelou, I.; Flouris, G.; Foudas, C.; Kokkas, P.; Manthos, N.; Papadopoulos, I.; Strologas, J.; Paradas, E.; Bencze, G.; Hajdu, C.; Hidas, P.; Horvath, D.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Zsigmond, A. J.; Beni, N.; Czellar, S.; Karancsi, J.; Molnar, J.; Palinkas, J.; Szillasi, Z.; Makovec, A.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Swain, S. K.; Beri, S. B.; Bhatnagar, V.; Gupta, R.; Bhawandeep, U.; Kalsi, A. K.; Kaur, M.; Kumar, R.; Mittal, M.; Nishu, N.; Singh, J. B.; Kumar, Ashok; Kumar, Arun; Ahuja, S.; Bhardwaj, A.; Choudhary, B. 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S.; Colaleo, A.; Creanza, D.; Cristella, L.; De Filippis, N.; De Palma, M.; Fiore, L.; Iaselli, G.; Maggi, G.; Maggi, M.; My, S.; Nuzzo, S.; Pompili, A.; Pugliese, G.; Radogna, R.; Selvaggi, G.; Sharma, A.; Silvestris, L.; Venditti, R.; Verwilligen, P.; Abbiendi, G.; Benvenuti, A. C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Brigliadori, L.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Codispoti, G.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Grandi, C.; Guiducci, L.; Marcellini, S.; Masetti, G.; Montanari, A.; Navarria, F. L.; Perrotta, A.; Rossi, A. M.; Rovelli, T.; Siroli, G. 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T.; Spagnolo, P.; Squillacioti, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Vernieri, C.; Barone, L.; Cavallari, F.; D'imperio, G.; Del Re, D.; Diemoz, M.; Jorda, C.; Longo, E.; Margaroli, F.; Meridiani, P.; Micheli, F.; Organtini, G.; Paramatti, R.; Rahatlou, S.; Rovelli, C.; Santanastasio, F.; Soffi, L.; Traczyk, P.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Bellan, R.; Biino, C.; Cartiglia, N.; Casasso, S.; Costa, M.; Covarelli, R.; Degano, A.; Demaria, N.; Finco, L.; Mariotti, C.; Maselli, S.; Migliore, E.; Monaco, V.; Musich, M.; Obertino, M. M.; Pacher, L.; Pastrone, N.; Pelliccioni, M.; Pinna Angioni, G. L.; Potenza, A.; Romero, A.; Ruspa, M.; Sacchi, R.; Solano, A.; Staiano, A.; Tamponi, U.; Belforte, S.; Candelise, V.; Casarsa, M.; Cossutti, F.; Della Ricca, G.; Gobbo, B.; La Licata, C.; Marone, M.; Schizzi, A.; Umer, T.; Zanetti, A.; Chang, S.; Kropivnitskaya, A.; Nam, S. K.; Kim, D. H.; Kim, G. N.; Kim, M. S.; Kim, M. S.; Kong, D. J.; Lee, S.; Oh, Y. D.; Park, H.; Sakharov, A.; Son, D. C.; Kim, T. J.; Ryu, M. S.; Kim, J. Y.; Moon, D. H.; Song, S.; Choi, S.; Gyun, D.; Hong, B.; Jo, M.; Kim, H.; Kim, Y.; Lee, B.; Lee, K. S.; Park, S. K.; Roh, Y.; Yoo, H. D.; Choi, M.; Kim, J. H.; Park, I. C.; Ryu, G.; Choi, Y.; Choi, Y. K.; Goh, J.; Kim, D.; Kwon, E.; Lee, J.; Yu, I.; Juodagalvis, A.; Komaragiri, J. R.; Md Ali, M. A. B.; Wan Abdullah, W. A. T.; Casimiro Linares, E.; Castilla-Valdez, H.; De La Cruz-Burelo, E.; Heredia-de La Cruz, I.; Hernandez-Almada, A.; Lopez-Fernandez, R.; Sanchez-Hernandez, A.; Carrillo Moreno, S.; Vazquez Valencia, F.; Pedraza, I.; Salazar Ibarguen, H. A.; Morelos Pineda, A.; Krofcheck, D.; Butler, P. H.; Reucroft, S.; Ahmad, A.; Ahmad, M.; Hassan, Q.; Hoorani, H. R.; Khan, W. A.; Khurshid, T.; Shoaib, M.; Bialkowska, H.; Bluj, M.; Boimska, B.; Frueboes, T.; Górski, M.; Kazana, M.; Nawrocki, K.; Romanowska-Rybinska, K.; Szleper, M.; Zalewski, P.; Brona, G.; Bunkowski, K.; Cwiok, M.; Dominik, W.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Misiura, M.; Olszewski, M.; Bargassa, P.; Beirão Da Cruz E Silva, C.; Di Francesco, A.; Faccioli, P.; Ferreira Parracho, P. G.; Gallinaro, M.; Lloret Iglesias, L.; Nguyen, F.; Rodrigues Antunes, J.; Seixas, J.; Toldaiev, O.; Vadruccio, D.; Varela, J.; Vischia, P.; Bunin, P.; Gavrilenko, M.; Golutvin, I.; Kamenev, A.; Karjavin, V.; Konoplyanikov, V.; Kozlov, G.; Lanev, A.; Malakhov, A.; Matveev, V.; Moisenz, P.; Palichik, V.; Perelygin, V.; Savina, M.; Shmatov, S.; Shulha, S.; Smirnov, V.; Zarubin, A.; Golovtsov, V.; Ivanov, Y.; Kim, V.; Kuznetsova, E.; Levchenko, P.; Murzin, V.; Oreshkin, V.; Smirnov, I.; Sulimov, V.; Uvarov, L.; Vavilov, S.; Vorobyev, A.; Vorobyev, An.; Andreev, Yu.; Dermenev, A.; Gninenko, S.; Golubev, N.; Kirsanov, M.; Krasnikov, N.; Pashenkov, A.; Tlisov, D.; Toropin, A.; Epshteyn, V.; Gavrilov, V.; Lychkovskaya, N.; Popov, V.; Pozdnyakov, I.; Safronov, G.; Semenov, S.; Spiridonov, A.; Stolin, V.; Vlasov, E.; Zhokin, A.; Andreev, V.; Azarkin, M.; Dremin, I.; Kirakosyan, M.; Leonidov, A.; Mesyats, G.; Rusakov, S. V.; Vinogradov, A.; Belyaev, A.; Boos, E.; Bunichev, V.; Dubinin, M.; Dudko, L.; Ershov, A.; Gribushin, A.; Klyukhin, V.; Kodolova, O.; Lokhtin, I.; Obraztsov, S.; Petrushanko, S.; Savrin, V.; Azhgirey, I.; Bayshev, I.; Bitioukov, S.; Kachanov, V.; Kalinin, A.; Konstantinov, D.; Krychkine, V.; Petrov, V.; Ryutin, R.; Sobol, A.; Tourtchanovitch, L.; Troshin, S.; Tyurin, N.; Uzunian, A.; Volkov, A.; Adzic, P.; Ekmedzic, M.; Milosevic, J.; Rekovic, V.; Alcaraz Maestre, J.; Battilana, C.; Calvo, E.; Cerrada, M.; Chamizo Llatas, M.; Colino, N.; De La Cruz, B.; Delgado Peris, A.; Domínguez Vázquez, D.; Escalante Del Valle, A.; Fernandez Bedoya, C.; Fernández Ramos, J. P.; Flix, J.; Fouz, M. C.; Garcia-Abia, P.; Gonzalez Lopez, O.; Goy Lopez, S.; Hernandez, J. M.; Josa, M. I.; Navarro De Martino, E.; Pérez-Calero Yzquierdo, A.; Puerta Pelayo, J.; Quintario Olmeda, A.; Redondo, I.; Romero, L.; Soares, M. S.; Albajar, C.; de Trocóniz, J. F.; Missiroli, M.; Moran, D.; Brun, H.; Cuevas, J.; Fernandez Menendez, J.; Folgueras, S.; Gonzalez Caballero, I.; Brochero Cifuentes, J. A.; Cabrillo, I. J.; Calderon, A.; Duarte Campderros, J.; Fernandez, M.; Gomez, G.; Graziano, A.; Lopez Virto, A.; Marco, J.; Marco, R.; Martinez Rivero, C.; Matorras, F.; Munoz Sanchez, F. J.; Piedra Gomez, J.; Rodrigo, T.; Rodríguez-Marrero, A. Y.; Ruiz-Jimeno, A.; Scodellaro, L.; Vila, I.; Vilar Cortabitarte, R.; Abbaneo, D.; Auffray, E.; Auzinger, G.; Bachtis, M.; Baillon, P.; Ball, A. H.; Barney, D.; Benaglia, A.; Bendavid, J.; Benhabib, L.; Benitez, J. F.; Bloch, P.; Bocci, A.; Bonato, A.; Bondu, O.; Botta, C.; Breuker, H.; Camporesi, T.; Cerminara, G.; Colafranceschi, S.; D'Alfonso, M.; d'Enterria, D.; Dabrowski, A.; David, A.; De Guio, F.; De Roeck, A.; De Visscher, S.; Di Marco, E.; Dobson, M.; Dordevic, M.; Dorney, B.; Dupont-Sagorin, N.; Elliott-Peisert, A.; Franzoni, G.; Funk, W.; Gigi, D.; Gill, K.; Giordano, D.; Girone, M.; Glege, F.; Guida, R.; Gundacker, S.; Guthoff, M.; Guida, R.; Hammer, J.; Hansen, M.; Harris, P.; Hegeman, J.; Innocente, V.; Janot, P.; Kortelainen, M. J.; Kousouris, K.; Krajczar, K.; Lecoq, P.; Lourenço, C.; Magini, N.; Malgeri, L.; Mannelli, M.; Marrouche, J.; Masetti, L.; Meijers, F.; Mersi, S.; Meschi, E.; Moortgat, F.; Morovic, S.; Mulders, M.; Orfanelli, S.; Orsini, L.; Pape, L.; Perez, E.; Petrilli, A.; Petrucciani, G.; Pfeiffer, A.; Pimiä, M.; Piparo, D.; Plagge, M.; Racz, A.; Rolandi, G.; Rovere, M.; Sakulin, H.; Schäfer, C.; Schwick, C.; Sharma, A.; Siegrist, P.; Silva, P.; Simon, M.; Sphicas, P.; Spiga, D.; Steggemann, J.; Stieger, B.; Stoye, M.; Takahashi, Y.; Treille, D.; Tsirou, A.; Veres, G. I.; Wardle, N.; Wöhri, H. K.; Wollny, H.; Zeuner, W. D.; Bertl, W.; Deiters, K.; Erdmann, W.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; Kotlinski, D.; Langenegger, U.; Renker, D.; Rohe, T.; Bachmair, F.; Bäni, L.; Bianchini, L.; Buchmann, M. A.; Casal, B.; Dissertori, G.; Dittmar, M.; Donegà, M.; Dünser, M.; Eller, P.; Grab, C.; Hits, D.; Hoss, J.; Kasieczka, G.; Lustermann, W.; Mangano, B.; Marini, A. C.; Marionneau, M.; Martinez Ruiz del Arbol, P.; Masciovecchio, M.; Meister, D.; Mohr, N.; Musella, P.; Nägeli, C.; Nessi-Tedaldi, F.; Pandolfi, F.; Pauss, F.; Perrozzi, L.; Peruzzi, M.; Quittnat, M.; Rebane, L.; Rossini, M.; Starodumov, A.; Takahashi, M.; Theofilatos, K.; Wallny, R.; Weber, H. A.; Amsler, C.; Canelli, M. F.; Chiochia, V.; De Cosa, A.; Hinzmann, A.; Hreus, T.; Kilminster, B.; Lange, C.; Ngadiuba, J.; Pinna, D.; Robmann, P.; Ronga, F. J.; Salerno, D.; Taroni, S.; Yang, Y.; Cardaci, M.; Chen, K. H.; Ferro, C.; Kuo, C. M.; Lin, W.; Lu, Y. J.; Volpe, R.; Yu, S. S.; Chang, P.; Chang, Y. H.; Chao, Y.; Chen, K. F.; Chen, P. H.; Dietz, C.; Grundler, U.; Hou, W.-S.; Liu, Y. F.; Lu, R.-S.; Miñano Moya, M.; Petrakou, E.; Tsai, J. f.; Tzeng, Y. M.; Wilken, R.; Asavapibhop, B.; Singh, G.; Srimanobhas, N.; Suwonjandee, N.; Adiguzel, A.; Bakirci, M. N.; Cerci, S.; Dozen, C.; Dumanoglu, I.; Eskut, E.; Girgis, S.; Gokbulut, G.; Guler, Y.; Gurpinar, E.; Hos, I.; Kangal, E. E.; Kayis Topaksu, A.; Onengut, G.; Ozdemir, K.; Ozturk, S.; Polatoz, A.; Sunar Cerci, D.; Tali, B.; Topakli, H.; Vergili, M.; Zorbilmez, C.; Akin, I. V.; Bilin, B.; Bilmis, S.; Gamsizkan, H.; Isildak, B.; Karapinar, G.; Ocalan, K.; Sekmen, S.; Surat, U. E.; Yalvac, M.; Zeyrek, M.; Albayrak, E. A.; Gülmez, E.; Kaya, M.; Kaya, O.; Yetkin, T.; Cankocak, K.; Vardarlı, F. I.; Levchuk, L.; Sorokin, P.; Brooke, J. J.; Clement, E.; Cussans, D.; Flacher, H.; Goldstein, J.; Grimes, M.; Heath, G. P.; Heath, H. F.; Jacob, J.; Kreczko, L.; Lucas, C.; Meng, Z.; Newbold, D. M.; Paramesvaran, S.; Poll, A.; Sakuma, T.; Seif El Nasr-storey, S.; Senkin, S.; Smith, V. J.; Williams, T.; Bell, K. W.; Belyaev, A.; Brew, C.; Brown, R. M.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Olaiya, E.; Petyt, D.; Shepherd-Themistocleous, C. H.; Thea, A.; Tomalin, I. R.; Williams, T.; Womersley, W. J.; Worm, S. D.; Baber, M.; Bainbridge, R.; Buchmuller, O.; Burton, D.; Colling, D.; Cripps, N.; Dauncey, P.; Davies, G.; De Wit, A.; Della Negra, M.; Dunne, P.; Elwood, A.; Ferguson, W.; Fulcher, J.; Futyan, D.; Hall, G.; Iles, G.; Jarvis, M.; Karapostoli, G.; Kenzie, M.; Lane, R.; Lucas, R.; Lyons, L.; Magnan, A.-M.; Malik, S.; Mathias, B.; Nash, J.; Nikitenko, A.; Pela, J.; Pesaresi, M.; Petridis, K.; Raymond, D. M.; Rogerson, S.; Rose, A.; Seez, C.; Sharp, P.; Tapper, A.; Vazquez Acosta, M.; Virdee, T.; Zenz, S. C.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Leggat, D.; Leslie, D.; Reid, I. D.; Symonds, P.; Teodorescu, L.; Turner, M.; Dittmann, J.; Hatakeyama, K.; Kasmi, A.; Liu, H.; Pastika, N.; Scarborough, T.; Wu, Z.; Charaf, O.; Cooper, S. I.; Henderson, C.; Rumerio, P.; Avetisyan, A.; Bose, T.; Fantasia, C.; Lawson, P.; Richardson, C.; Rohlf, J.; St. John, J.; Sulak, L.; Zou, D.; Alimena, J.; Berry, E.; Bhattacharya, S.; Christopher, G.; Cutts, D.; Demiragli, Z.; Dhingra, N.; Ferapontov, A.; Garabedian, A.; Heintz, U.; Laird, E.; Landsberg, G.; Mao, Z.; Narain, M.; Sagir, S.; Sinthuprasith, T.; Speer, T.; Swanson, J.; Breedon, R.; Breto, G.; Calderon De La Barca Sanchez, M.; Chauhan, S.; Chertok, M.; Conway, J.; Conway, R.; Cox, P. T.; Erbacher, R.; Gardner, M.; Ko, W.; Lander, R.; Mulhearn, M.; Pellett, D.; Pilot, J.; Ricci-Tam, F.; Shalhout, S.; Smith, J.; Squires, M.; Stolp, D.; Tripathi, M.; Wilbur, S.; Yohay, R.; Cousins, R.; Everaerts, P.; Farrell, C.; Hauser, J.; Ignatenko, M.; Rakness, G.; Takasugi, E.; Valuev, V.; Weber, M.; Burt, K.; Clare, R.; Ellison, J.; Gary, J. W.; Hanson, G.; Heilman, J.; Ivova Rikova, M.; Jandir, P.; Kennedy, E.; Lacroix, F.; Long, O. R.; Luthra, A.; Malberti, M.; Negrete, M. Olmedo; Shrinivas, A.; Sumowidagdo, S.; Wimpenny, S.; Branson, J. G.; Cerati, G. B.; Cittolin, S.; D'Agnolo, R. T.; Holzner, A.; Kelley, R.; Klein, D.; Letts, J.; Macneill, I.; Olivito, D.; Padhi, S.; Palmer, C.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Tadel, M.; Tu, Y.; Vartak, A.; Welke, C.; Würthwein, F.; Yagil, A.; Zevi Della Porta, G.; Barge, D.; Bradmiller-Feld, J.; Campagnari, C.; Danielson, T.; Dishaw, A.; Dutta, V.; Flowers, K.; Franco Sevilla, M.; Geffert, P.; George, C.; Golf, F.; Gouskos, L.; Incandela, J.; Justus, C.; Mccoll, N.; Mullin, S. D.; Richman, J.; Stuart, D.; To, W.; West, C.; Yoo, J.; Apresyan, A.; Bornheim, A.; Bunn, J.; Chen, Y.; Duarte, J.; Mott, A.; Newman, H. B.; Pena, C.; Pierini, M.; Spiropulu, M.; Vlimant, J. R.; Wilkinson, R.; Xie, S.; Zhu, R. Y.; Azzolini, V.; Calamba, A.; Carlson, B.; Ferguson, T.; Iiyama, Y.; Paulini, M.; Russ, J.; Vogel, H.; Vorobiev, I.; Cumalat, J. P.; Ford, W. T.; Gaz, A.; Krohn, M.; Luiggi Lopez, E.; Nauenberg, U.; Smith, J. G.; Stenson, K.; Wagner, S. R.; Alexander, J.; Chatterjee, A.; Chaves, J.; Chu, J.; Dittmer, S.; Eggert, N.; Mirman, N.; Nicolas Kaufman, G.; Patterson, J. R.; Ryd, A.; Salvati, E.; Skinnari, L.; Sun, W.; Teo, W. D.; Thom, J.; Thompson, J.; Tucker, J.; Weng, Y.; Winstrom, L.; Wittich, P.; Winn, D.; Abdullin, S.; Albrow, M.; Anderson, J.; Apollinari, G.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Bolla, G.; Burkett, K.; Butler, J. N.; Cheung, H. W. K.; Chlebana, F.; Cihangir, S.; Elvira, V. D.; Fisk, I.; Freeman, J.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Hanlon, J.; Hare, D.; Harris, R. M.; Hirschauer, J.; Hooberman, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Klima, B.; Kreis, B.; Kwan, S.; Linacre, J.; Lincoln, D.; Lipton, R.; Liu, T.; Lopes De Sá, R.; Lykken, J.; Maeshima, K.; Marraffino, J. M.; Martinez Outschoorn, V. I.; Maruyama, S.; Mason, D.; McBride, P.; Merkel, P.; Mishra, K.; Mrenna, S.; Nahn, S.; Newman-Holmes, C.; O'Dell, V.; Prokofyev, O.; Sexton-Kennedy, E.; Soha, A.; Spalding, W. J.; Spiegel, L.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vidal, R.; Whitbeck, A.; Whitmore, J.; Yang, F.; Acosta, D.; Avery, P.; Bortignon, P.; Bourilkov, D.; Carver, M.; Curry, D.; Das, S.; De Gruttola, M.; Di Giovanni, G. P.; Field, R. D.; Fisher, M.; Furic, I. K.; Hugon, J.; Konigsberg, J.; Korytov, A.; Kypreos, T.; Low, J. F.; Matchev, K.; Mei, H.; Milenovic, P.; Mitselmakher, G.; Muniz, L.; Rinkevicius, A.; Shchutska, L.; Snowball, M.; Sperka, D.; Yelton, J.; Zakaria, M.; Hewamanage, S.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Adams, J. R.; Adams, T.; Askew, A.; Bochenek, J.; Diamond, B.; Haas, J.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Prosper, H.; Veeraraghavan, V.; Weinberg, M.; Baarmand, M. M.; Hohlmann, M.; Kalakhety, H.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Bucinskaite, I.; Cavanaugh, R.; Evdokimov, O.; Gauthier, L.; Gerber, C. E.; Hofman, D. J.; Kurt, P.; O'Brien, C.; Sandoval Gonzalez, I. D.; Silkworth, C.; Turner, P.; Varelas, N.; Bilki, B.; Clarida, W.; Dilsiz, K.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Rahmat, R.; Sen, S.; Tan, P.; Tiras, E.; Wetzel, J.; Yi, K.; Anderson, I.; Barnett, B. A.; Blumenfeld, B.; Bolognesi, S.; Fehling, D.; Gritsan, A. V.; Maksimovic, P.; Martin, C.; Swartz, M.; Xiao, M.; Baringer, P.; Bean, A.; Benelli, G.; Bruner, C.; Gray, J.; Kenny, R. P.; Majumder, D.; Malek, M.; Murray, M.; Noonan, D.; Sanders, S.; Sekaric, J.; Stringer, R.; Wang, Q.; Wood, J. S.; Chakaberia, I.; Ivanov, A.; Kaadze, K.; Khalil, S.; Makouski, M.; Maravin, Y.; Saini, L. K.; Skhirtladze, N.; Svintradze, I.; Gronberg, J.; Lange, D.; Rebassoo, F.; Wright, D.; Anelli, C.; Baden, A.; Belloni, A.; Calvert, B.; Eno, S. C.; Gomez, J. A.; Hadley, N. J.; Jabeen, S.; Kellogg, R. G.; Kolberg, T.; Lu, Y.; Mignerey, A. C.; Pedro, K.; Shin, Y. H.; Skuja, A.; Tonjes, M. B.; Tonwar, S. C.; Apyan, A.; Barbieri, R.; Baty, A.; Bierwagen, K.; Brandt, S.; Busza, W.; Cali, I. A.; Di Matteo, L.; Gomez Ceballos, G.; Goncharov, M.; Gulhan, D.; Klute, M.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Paus, C.; Ralph, D.; Roland, C.; Roland, G.; Stephans, G. S. F.; Sumorok, K.; Velicanu, D.; Veverka, J.; Wyslouch, B.; Yang, M.; Yoon, A. S.; Zanetti, M.; Zhukova, V.; Dahmes, B.; De Benedetti, A.; Gude, A.; Kao, S. C.; Klapoetke, K.; Kubota, Y.; Mans, J.; Nourbakhsh, S.; Rusack, R.; Singovsky, A.; Tambe, N.; Turkewitz, J.; Acosta, J. G.; Cremaldi, L. M.; Kroeger, R.; Oliveros, S.; Perera, L.; Sanders, D. A.; Summers, D.; Avdeeva, E.; Bloom, K.; Bose, S.; Claes, D. R.; Dominguez, A.; Gonzalez Suarez, R.; Keller, J.; Knowlton, D.; Kravchenko, I.; Lazo-Flores, J.; Meier, F.; Ratnikov, F.; Snow, G. R.; Zvada, M.; Dolen, J.; Godshalk, A.; Iashvili, I.; Jain, S.; Kharchilava, A.; Kumar, A.; Rappoccio, S.; Alverson, G.; Barberis, E.; Baumgartel, D.; Chasco, M.; Massironi, A.; Nash, D.; Orimoto, T.; Trocino, D.; Wood, D.; Zhang, J.; Anastassov, A.; Hahn, K. A.; Kubik, A.; Lusito, L.; Mucia, N.; Odell, N.; Pollack, B.; Pozdnyakov, A.; Schmitt, M.; Stoynev, S.; Sung, K.; Trovato, M.; Velasco, M.; Won, S.; Brinkerhoff, A.; Chan, K. M.; Drozdetskiy, A.; Hildreth, M.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Lynch, S.; Marinelli, N.; Musienko, Y.; Pearson, T.; Planer, M.; Ruchti, R.; Valls, N.; Smith, G.; Wayne, M.; Wolf, M.; Woodard, A.; Antonelli, L.; Brinson, J.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Hart, A.; Hill, C.; Hughes, R.; Kotov, K.; Ling, T. Y.; Luo, W.; Puigh, D.; Rodenburg, M.; Winer, B. L.; Wolfe, H.; Wulsin, H. W.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Koay, S. A.; Lujan, P.; Marlow, D.; Medvedeva, T.; Mooney, M.; Olsen, J.; Piroué, P.; Quan, X.; Saka, H.; Stickland, D.; Tully, C.; Werner, J. S.; Zuranski, A.; Brownson, E.; Malik, S.; Mendez, H.; Ramirez Vargas, J. E.; Barnes, V. E.; Benedetti, D.; Bortoletto, D.; Gutay, L.; Hu, Z.; Jha, M. K.; Jones, M.; Jung, K.; Kress, M.; Leonardo, N.; Miller, D. H.; Neumeister, N.; Primavera, F.; Radburn-Smith, B. C.; Shi, X.; Shipsey, I.; Silvers, D.; Svyatkovskiy, A.; Wang, F.; Xie, W.; Xu, L.; Zablocki, J.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Ecklund, K. M.; Geurts, F. J. M.; Li, W.; Michlin, B.; Padley, B. P.; Redjimi, R.; Roberts, J.; Zabel, J.; Betchart, B.; Bodek, A.; de Barbaro, P.; Demina, R.; Eshaq, Y.; Ferbel, T.; Galanti, M.; Garcia-Bellido, A.; Goldenzweig, P.; Han, J.; Harel, A.; Hindrichs, O.; Khukhunaishvili, A.; Korjenevski, S.; Petrillo, G.; Verzetti, M.; Vishnevskiy, D.; Ciesielski, R.; Demortier, L.; Goulianos, K.; Mesropian, C.; Arora, S.; Barker, A.; Chou, J. P.; Contreras-Campana, C.; Contreras-Campana, E.; Duggan, D.; Ferencek, D.; Gershtein, Y.; Gray, R.; Halkiadakis, E.; Hidas, D.; Hughes, E.; Kaplan, S.; Kunnawalkam Elayavalli, R.; Lath, A.; Panwalkar, S.; Park, M.; Salur, S.; Schnetzer, S.; Sheffield, D.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Rose, K.; Spanier, S.; York, A.; Bouhali, O.; Castaneda Hernandez, A.; Dalchenko, M.; De Mattia, M.; Dildick, S.; Eusebi, R.; Flanagan, W.; Gilmore, J.; Kamon, T.; Khotilovich, V.; Krutelyov, V.; Montalvo, R.; Osipenkov, I.; Pakhotin, Y.; Patel, R.; Perloff, A.; Roe, J.; Rose, A.; Safonov, A.; Suarez, I.; Tatarinov, A.; Ulmer, K. A.; Akchurin, N.; Cowden, C.; Damgov, J.; Dragoiu, C.; Dudero, P. R.; Faulkner, J.; Kovitanggoon, K.; Kunori, S.; Lee, S. W.; Libeiro, T.; Volobouev, I.; Appelt, E.; Delannoy, A. G.; Greene, S.; Gurrola, A.; Johns, W.; Maguire, C.; Mao, Y.; Melo, A.; Sharma, M.; Sheldon, P.; Snook, B.; Tuo, S.; Velkovska, J.; Arenton, M. W.; Boutle, S.; Cox, B.; Francis, B.; Goodell, J.; Hirosky, R.; Ledovskoy, A.; Li, H.; Lin, C.; Neu, C.; Wolfe, E.; Wood, J.; Clarke, C.; Harr, R.; Karchin, P. E.; Kottachchi Kankanamge Don, C.; Lamichhane, P.; Sturdy, J.; Belknap, D. A.; Carlsmith, D.; Cepeda, M.; Dasu, S.; Dodd, L.; Duric, S.; Friis, E.; Hall-Wilton, R.; Herndon, M.; Hervé, A.; Klabbers, P.; Lanaro, A.; Lazaridis, C.; Levine, A.; Loveless, R.; Mohapatra, A.; Ojalvo, I.; Perry, T.; Pierro, G. A.; Polese, G.; Ross, I.; Sarangi, T.; Savin, A.; Smith, W. H.; Taylor, D.; Vuosalo, C.; Woods, N.; CMS Collaboration

2015-06-01

A search for a standard model Higgs boson produced in association with a top-quark pair and decaying to bottom quarks is presented. Events with hadronic jets and one or two oppositely charged leptons are selected from a data sample corresponding to an integrated luminosity of 19.5 collected by the CMS experiment at the LHC in collisions at a centre-of-mass energy of 8. In order to separate the signal from the larger + jets background, this analysis uses a matrix element method that assigns a probability density value to each reconstructed event under signal or background hypotheses. The ratio between the two values is used in a maximum likelihood fit to extract the signal yield. The results are presented in terms of the measured signal strength modifier, , relative to the standard model prediction for a Higgs boson mass of 125. The observed (expected) exclusion limit at a 95 % confidence level is (3.3), corresponding to a best fit value.

From molecular noise to behavioural variability in a single bacterium

NASA Astrophysics Data System (ADS)

Korobkova, Ekaterina; Emonet, Thierry; Vilar, Jose M. G.; Shimizu, Thomas S.; Cluzel, Philippe

2004-04-01

The chemotaxis network that governs the motion of Escherichia coli has long been studied to gain a general understanding of signal transduction. Although this pathway is composed of just a few components, it exhibits some essential characteristics of biological complexity, such as adaptation and response to environmental signals. In studying intracellular networks, most experiments and mathematical models have assumed that network properties can be inferred from population measurements. However, this approach masks underlying temporal fluctuations of intracellular signalling events. We have inferred fundamental properties of the chemotaxis network from a noise analysis of behavioural variations in individual bacteria. Here we show that certain properties established by population measurements, such as adapted states, are not conserved at the single-cell level: for timescales ranging from seconds to several minutes, the behaviour of non-stimulated cells exhibit temporal variations much larger than the expected statistical fluctuations. We find that the signalling network itself causes this noise and identify the molecular events that produce it. Small changes in the concentration of one key network component suppress temporal behavioural variability, suggesting that such variability is a selected property of this adaptive system.

The experimental research on response characteristics of coal samples under the uniaxial loading process

NASA Astrophysics Data System (ADS)

Jia, Bing; Wei, Jian-Ping; Wen, Zhi-Hui; Wang, Yun-Gang; Jia, Lin-Xing

2017-11-01

In order to study the response characteristics of infrasound in coal samples under the uniaxial loading process, coal samples were collected from GengCun mine. Coal rock stress loading device, acoustic emission tested system and infrasound tested system were used to test the infrasonic signal and acoustic emission signal under uniaxial loading process. The tested results were analyzed by the methods of wavelet filter, threshold denoise, time-frequency analysis and so on. The results showed that in the loading process, the change of the infrasonic wave displayed the characteristics of stage, and it could be divided into three stages: initial stage with a certain amount infrasound events, middle stage with few infrasound events, and late stage gradual decrease. It had a good consistency with changing characteristics of acoustic emission. At the same time, the frequency of infrasound was very low. It can propagate over a very long distance with little attenuation, and the characteristics of the infrasound before the destruction of the coal samples were obvious. A method of using the infrasound characteristics to predict the destruction of coal samples was proposed. This is of great significance to guide the prediction of geological hazards in coal mines.

Enhanced spontaneous Ca2+ events in endothelial cells reflect signalling through myoendothelial gap junctions in pressurized mesenteric arteries.

PubMed

Kansui, Yasuo; Garland, Christopher J; Dora, Kim A

2008-08-01

Increases in global Ca(2+) in the endothelium are a crucial step in releasing relaxing factors to modulate arterial tone. In the present study we investigated spontaneous Ca(2+) events in endothelial cells, and the contribution of smooth muscle cells to these Ca(2+) events, in pressurized rat mesenteric resistance arteries. Spontaneous Ca(2+) events were observed under resting conditions in 34% of cells. These Ca(2+) events were absent in arteries preincubated with either cyclopiazonic acid or U-73122, but were unaffected by ryanodine or nicotinamide. Stimulation of smooth muscle cell depolarization and contraction with either phenylephrine or high concentrations of KCl significantly increased the frequency of endothelial cell Ca(2+) events. The putative gap junction uncouplers carbenoxolone and 18alpha-glycyrrhetinic acid each inhibited spontaneous and evoked Ca(2+) events, and the movement of calcein from endothelial to smooth muscle cells. In addition, spontaneous Ca(2+) events were diminished by nifedipine, lowering extracellular Ca(2+) levels, or by blockers of non-selective Ca(2+) influx pathways. These findings suggest that in pressurized rat mesenteric arteries, spontaneous Ca(2+) events in the endothelial cells appear to originate from endoplasmic reticulum IP(3) receptors, and are subject to regulation by surrounding smooth muscle cells via myoendothelial gap junctions, even under basal conditions.

Rotary pin-in-maze discriminator

DOEpatents

Benavides, Gilbert L.

1997-01-01

A discriminator apparatus and method that discriminates between a unique signal and any other (incorrect) signal. The unique signal is a sequence of events; each event can assume one of two possible event states. Given the unique signal, a maze wheel is allowed to rotate fully in one direction. Given an incorrect signal, both the maze wheel and a pin wheel lock in position.

Quirks at the Tevatron and Beyond

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harnik, Roni; /Fermilab; Kribs, Graham D.

2011-06-01

We consider the physics and collider phenomenology of quirks that transform nontrivially under QCD color, SU(2){sub W} as well as an SU(N){sub ic} infracolor group. Our main motivation is to show that the recent Wjj excess observed by CDF naturally arises in quirky models. The basic pattern is that several different quirky states can be produced, some of which {beta} decay during or after spin-down, leaving the lightest electrically-neutral quirks to hadronize into a meson that subsequently decays into gluon jets. We analyze LEP II, Tevatron, UA2, and electroweak precision constraints, identifying the simplest viable models: scalar quirks ('squirks') transformingmore » as color triplets, SU(2){sub W} triplets and singlets, all with vanishing hypercharge. We calculate production cross sections, weak decay, spin-down, meson decay rates, and estimate efficiencies. The novel features of our quirky model includes: quirkonium decay proceeds into a pair of gluon jets, without a b-jet component; there is essentially no associated Zjj or {gamma}jj signal; and there are potentially new (parameter-dependent) contributions to dijet production, multi-W production plus jets, W{gamma}, {gamma}{gamma} resonance signals, and monojet signals. There may be either underlying event from low energy QCD deposition resulting from quirky spin-down and/or qualitatively modified event kinematics from infraglueball emission.« less

Deciphering the desiccation trend of the South Asian monsoon hydroclimate in a warming world

NASA Astrophysics Data System (ADS)

Krishnan, R.; Sabin, T. P.; Vellore, R.; Mujumdar, M.; Sanjay, J.; Goswami, B. N.; Hourdin, F.; Dufresne, J.-L.; Terray, P.

2016-08-01

Rising propensity of precipitation extremes and concomitant decline of summer-monsoon rains are amongst the most distinctive hydroclimatic signals that have emerged over South Asia since 1950s. A clear understanding of the underlying causes driving these monsoon hydroclimatic signals has remained elusive. Using a state-of-the-art global climate model with high-resolution zooming over South Asia, we demonstrate that a juxtaposition of regional land-use changes, anthropogenic-aerosol forcing and the rapid warming signal of the equatorial Indian Ocean is crucial to produce the observed monsoon weakening in recent decades. Our findings also show that this monsoonal weakening significantly enhances occurrence of localized intense precipitation events, as compared to the global-warming response. A 21st century climate projection using the same high-resolution model indicates persistent decrease of monsoonal rains and prolongation of soil drying. Critical value-additions from this study include (1) realistic simulation of the mean and long-term historical trends in the Indian monsoon rainfall (2) robust attributions of changes in moderate and heavy precipitation events over Central India (3) a 21st century projection of drying trend of the South Asian monsoon. The present findings have profound bearing on the regional water-security, which is already under severe hydrological-stress.

Discrete wavelet-aided delineation of PCG signal events via analysis of an area curve length-based decision statistic.

PubMed

Homaeinezhad, M R; Atyabi, S A; Daneshvar, E; Ghaffari, A; Tahmasebi, M

2010-12-01

The aim of this study is to describe a robust unified framework for segmentation of the phonocardiogram (PCG) signal sounds based on the false-alarm probability (FAP) bounded segmentation of a properly calculated detection measure. To this end, first the original PCG signal is appropriately pre-processed and then, a fixed sample size sliding window is moved on the pre-processed signal. In each slid, the area under the excerpted segment is multiplied by its curve-length to generate the Area Curve Length (ACL) metric to be used as the segmentation decision statistic (DS). Afterwards, histogram parameters of the nonlinearly enhanced DS metric are used for regulation of the α-level Neyman-Pearson classifier for FAP-bounded delineation of the PCG events. The proposed method was applied to all 85 records of Nursing Student Heart Sounds database (NSHSDB) including stenosis, insufficiency, regurgitation, gallop, septal defect, split sound, rumble, murmur, clicks, friction rub and snap disorders with different sampling frequencies. Also, the method was applied to the records obtained from an electronic stethoscope board designed for fulfillment of this study in the presence of high-level power-line noise and external disturbing sounds and as the results, no false positive (FP) or false negative (FN) errors were detected. High noise robustness, acceptable detection-segmentation accuracy of PCG events in various cardiac system conditions, and having no parameters dependency to the acquisition sampling frequency can be mentioned as the principal virtues and abilities of the proposed ACL-based PCG events detection-segmentation algorithm.

Endocytosis and Signaling during Development

PubMed Central

Bökel, Christian

2014-01-01

The development of multicellular organisms relies on an intricate choreography of intercellular communication events that pattern the embryo and coordinate the formation of tissues and organs. It is therefore not surprising that developmental biology, especially using genetic model organisms, has contributed significantly to the discovery and functional dissection of the associated signal-transduction cascades. At the same time, biophysical, biochemical, and cell biological approaches have provided us with insights into the underlying cell biological machinery. Here we focus on how endocytic trafficking of signaling components (e.g., ligands or receptors) controls the generation, propagation, modulation, reception, and interpretation of developmental signals. A comprehensive enumeration of the links between endocytosis and signal transduction would exceed the limits of this review. We will instead use examples from different developmental pathways to conceptually illustrate the various functions provided by endocytic processes during key steps of intercellular signaling. PMID:24591521

Microseismic Event Relocation and Focal Mechanism Estimation Based on PageRank Linkage

NASA Astrophysics Data System (ADS)

Aguiar, A. C.; Myers, S. C.

2017-12-01

Microseismicity associated with enhanced geothermal systems (EGS) is key in understanding how subsurface stimulation can modify stress, fracture rock, and increase permeability. Large numbers of microseismic events are commonly associated with hydroshearing an EGS, making data mining methods useful in their analysis. We focus on PageRank, originally developed as Google's search engine, and subsequently adapted for use in seismology to detect low-frequency earthquakes by linking events directly and indirectly through cross-correlation (Aguiar and Beroza, 2014). We expand on this application by using PageRank to define signal-correlation topology for micro-earthquakes from the Newberry Volcano EGS in Central Oregon, which has been stimulated two times using high-pressure fluid injection. We create PageRank signal families from both data sets and compare these to the spatial and temporal proximity of associated earthquakes. PageRank families are relocated using differential travel times measured by waveform cross-correlation (CC) and the Bayesloc approach (Myers et al., 2007). Prior to relocation events are loosely clustered with events at a distance from the cluster. After relocation, event families are found to be tightly clustered. Indirect linkage of signals using PageRank is a reliable way to increase the number of events confidently determined to be similar, suggesting an efficient and effective grouping of earthquakes with similar physical characteristics (ie. location, focal mechanism, stress drop). We further explore the possibility of using PageRank families to identify events with similar relative phase polarities and estimate focal mechanisms following Shelly et al. (2016) method, where CC measurements are used to determine individual polarities within event clusters. Given a positive result, PageRank might be a useful tool in adaptive approaches to enhance production at well-instrumented geothermal sites. Prepared by LLNL under Contract DE-AC52-07NA27344. LLNL-ABS-722404.

The signatures of acoustic emission waveforms from fatigue crack advancing in thin metallic plates

NASA Astrophysics Data System (ADS)

Yeasin Bhuiyan, Md; Giurgiutiu, Victor

2018-01-01

The acoustic emission (AE) waveforms from a fatigue crack advancing in a thin metallic plate possess diverse and complex spectral signatures. In this article, we analyze these waveform signatures in coordination with the load level during cyclic fatigue. The advancing fatigue crack may generate numerous AE hits while it grows under fatigue loading. We found that these AE hits can be sorted into various groups based on their AE waveform signatures. Each waveform group has a particular time-domain signal pattern and a specific frequency spectrum. This indicates that each group represents a certain AE event related to the fatigue crack growth behavior. In situ AE-fatigue experiments were conducted to monitor the fatigue crack growth with simultaneous measurement of AE signals, fatigue loading, and optical crack growth measurement. An in situ microscope was installed in the load-frame of the mechanical testing system (MTS) to optically monitor the fatigue crack growth and relate the AE signals with the crack growth measurement. We found the AE signal groups at higher load levels (75%-85% of maximum load) were different from the AE signal groups that happened at lower load levels (below 60% of load level). These AE waveform groups are highly related to the fatigue crack-related AE events. These AE signals mostly contain the higher frequency peaks (100 kHz, 230 kHz, 450 kHz, 550 kHz). Some AE signal groups happened as a clustered form that relates a sequence of small AE events within the fatigue crack. They happened at relatively lower load level (50%-60% of the maximum load). These AE signal groups may be related to crack friction and micro-fracture during the friction process. These AE signals mostly contain the lower frequency peaks (60 kHz, 100 kHz, 200 kHz). The AE waveform based analysis may give us comprehensive information of the metal fatigue.

Alternative Splicing Substantially Diversifies the Transcriptome during Early Photomorphogenesis and Correlates with the Energy Availability in Arabidopsis.

PubMed

Hartmann, Lisa; Drewe-Boß, Philipp; Wießner, Theresa; Wagner, Gabriele; Geue, Sascha; Lee, Hsin-Chieh; Obermüller, Dominik M; Kahles, André; Behr, Jonas; Sinz, Fabian H; Rätsch, Gunnar; Wachter, Andreas

2016-11-01

Plants use light as source of energy and information to detect diurnal rhythms and seasonal changes. Sensing changing light conditions is critical to adjust plant metabolism and to initiate developmental transitions. Here, we analyzed transcriptome-wide alterations in gene expression and alternative splicing (AS) of etiolated seedlings undergoing photomorphogenesis upon exposure to blue, red, or white light. Our analysis revealed massive transcriptome reprogramming as reflected by differential expression of ∼20% of all genes and changes in several hundred AS events. For more than 60% of all regulated AS events, light promoted the production of a presumably protein-coding variant at the expense of an mRNA with nonsense-mediated decay-triggering features. Accordingly, AS of the putative splicing factor REDUCED RED-LIGHT RESPONSES IN CRY1CRY2 BACKGROUND1, previously identified as a red light signaling component, was shifted to the functional variant under light. Downstream analyses of candidate AS events pointed at a role of photoreceptor signaling only in monochromatic but not in white light. Furthermore, we demonstrated similar AS changes upon light exposure and exogenous sugar supply, with a critical involvement of kinase signaling. We propose that AS is an integration point of signaling pathways that sense and transmit information regarding the energy availability in plants. © 2016 American Society of Plant Biologists. All rights reserved.

G-protein-coupled receptors signaling pathways in new antiplatelet drug development.

PubMed

Gurbel, Paul A; Kuliopulos, Athan; Tantry, Udaya S

2015-03-01

Platelet G-protein-coupled receptors influence platelet function by mediating the response to various agonists, including ADP, thromboxane A2, and thrombin. Blockade of the ADP receptor, P2Y12, in combination with cyclooxygenase-1 inhibition by aspirin has been among the most widely used pharmacological strategies to reduce cardiovascular event occurrence in high-risk patients. The latter dual pathway blockade strategy is one of the greatest advances in the field of cardiovascular medicine. In addition to P2Y12, the platelet thrombin receptor, protease activated receptor-1, has also been recently targeted for inhibition. Blockade of protease activated receptor-1 has been associated with reduced thrombotic event occurrence when added to a strategy using P2Y12 and cyclooxygenase-1 inhibition. At this time, the relative contributions of these G-protein-coupled receptor signaling pathways to in vivo thrombosis remain incompletely defined. The observation of treatment failure in ≈10% of high-risk patients treated with aspirin and potent P2Y12 inhibitors provides the rationale for targeting novel pathways mediating platelet function. Targeting intracellular signaling downstream from G-protein-coupled receptor receptors with phosphotidylionisitol 3-kinase and Gq inhibitors are among the novel strategies under investigation to prevent arterial ischemic event occurrence. Greater understanding of the mechanisms of G-protein-coupled receptor-mediated signaling may allow the tailoring of antiplatelet therapy. © 2015 American Heart Association, Inc.

Subsurface event detection and classification using Wireless Signal Networks.

PubMed

Yoon, Suk-Un; Ghazanfari, Ehsan; Cheng, Liang; Pamukcu, Sibel; Suleiman, Muhannad T

2012-11-05

Subsurface environment sensing and monitoring applications such as detection of water intrusion or a landslide, which could significantly change the physical properties of the host soil, can be accomplished using a novel concept, Wireless Signal Networks (WSiNs). The wireless signal networks take advantage of the variations of radio signal strength on the distributed underground sensor nodes of WSiNs to monitor and characterize the sensed area. To characterize subsurface environments for event detection and classification, this paper provides a detailed list and experimental data of soil properties on how radio propagation is affected by soil properties in subsurface communication environments. Experiments demonstrated that calibrated wireless signal strength variations can be used as indicators to sense changes in the subsurface environment. The concept of WSiNs for the subsurface event detection is evaluated with applications such as detection of water intrusion, relative density change, and relative motion using actual underground sensor nodes. To classify geo-events using the measured signal strength as a main indicator of geo-events, we propose a window-based minimum distance classifier based on Bayesian decision theory. The window-based classifier for wireless signal networks has two steps: event detection and event classification. With the event detection, the window-based classifier classifies geo-events on the event occurring regions that are called a classification window. The proposed window-based classification method is evaluated with a water leakage experiment in which the data has been measured in laboratory experiments. In these experiments, the proposed detection and classification method based on wireless signal network can detect and classify subsurface events.

Subsurface Event Detection and Classification Using Wireless Signal Networks

PubMed Central

Yoon, Suk-Un; Ghazanfari, Ehsan; Cheng, Liang; Pamukcu, Sibel; Suleiman, Muhannad T.

2012-01-01

Subsurface environment sensing and monitoring applications such as detection of water intrusion or a landslide, which could significantly change the physical properties of the host soil, can be accomplished using a novel concept, Wireless Signal Networks (WSiNs). The wireless signal networks take advantage of the variations of radio signal strength on the distributed underground sensor nodes of WSiNs to monitor and characterize the sensed area. To characterize subsurface environments for event detection and classification, this paper provides a detailed list and experimental data of soil properties on how radio propagation is affected by soil properties in subsurface communication environments. Experiments demonstrated that calibrated wireless signal strength variations can be used as indicators to sense changes in the subsurface environment. The concept of WSiNs for the subsurface event detection is evaluated with applications such as detection of water intrusion, relative density change, and relative motion using actual underground sensor nodes. To classify geo-events using the measured signal strength as a main indicator of geo-events, we propose a window-based minimum distance classifier based on Bayesian decision theory. The window-based classifier for wireless signal networks has two steps: event detection and event classification. With the event detection, the window-based classifier classifies geo-events on the event occurring regions that are called a classification window. The proposed window-based classification method is evaluated with a water leakage experiment in which the data has been measured in laboratory experiments. In these experiments, the proposed detection and classification method based on wireless signal network can detect and classify subsurface events. PMID:23202191

Surprise disrupts cognition via a fronto-basal ganglia suppressive mechanism

PubMed Central

Wessel, Jan R.; Jenkinson, Ned; Brittain, John-Stuart; Voets, Sarah H. E. M.; Aziz, Tipu Z.; Aron, Adam R.

2016-01-01

Surprising events markedly affect behaviour and cognition, yet the underlying mechanism is unclear. Surprise recruits a brain mechanism that globally suppresses motor activity, ostensibly via the subthalamic nucleus (STN) of the basal ganglia. Here, we tested whether this suppressive mechanism extends beyond skeletomotor suppression and also affects cognition (here, verbal working memory, WM). We recorded scalp-EEG (electrophysiology) in healthy participants and STN local field potentials in Parkinson's patients during a task in which surprise disrupted WM. For scalp-EEG, surprising events engage the same independent neural signal component that indexes action stopping in a stop-signal task. Importantly, the degree of this recruitment mediates surprise-related WM decrements. Intracranially, STN activity is also increased post surprise, especially when WM is interrupted. These results suggest that surprise interrupts cognition via the same fronto-basal ganglia mechanism that interrupts action. This motivates a new neural theory of how cognition is interrupted, and how distraction arises after surprising events. PMID:27088156

Rotary pin-in-maze discriminator

DOEpatents

Benavides, G.L.

1997-05-06

A discriminator apparatus and method that discriminates between a unique signal and any other (incorrect) signal are disclosed. The unique signal is a sequence of events; each event can assume one of two possible event states. Given the unique signal, a maze wheel is allowed to rotate fully in one direction. Given an incorrect signal, both the maze wheel and a pin wheel lock in position. 4 figs.

Extraction of AE events to estimate their b values under a triaxial compressive condition Examination using continuous broadband records

NASA Astrophysics Data System (ADS)

Yoneda, N.; Kawakata, H.; Hirano, S.; Yoshimitsu, N.; Takahashi, N.

2017-12-01

Seismic b values estimated in previous laboratory compressive tests had been utilized for natural earthquake studies. Randomly sampled enough number of events over a wide magnitude range are essential for accurate b value estimation. In former triaxial tests, PZTs had sensitivity only in a narrow frequency range. In addition, the recording system could not extract all signals because of mask times or threshold setting. Recently, Yoshimitsu et al. (2014) enabled to use broadband transducers under triaxial conditions and achieved to acquire waveforms continuously in several hours. With such a system, they estimated the seismic moment of AE at very small magnitude scale. We expected that their continuous broadband recording system made it possible to record much more AE with a wider magnitude range for credible b value estimation in a laboratory. In this study, we performed a compressive test under a higher confining pressure as an updated experiment of Yoshimitsu et al. (2014) and extracted an enough amount of AE. We prepared an intact cylindrical Westerly Granite sample, 100 mm long by 50 mm in diameter. We conducted a triaxial compressive test under a confining pressure of 50 MPa, at a room temperature with drying conditions. Seven broadband transducers (sensitive range; 100 kHz - 1,000 kHz) were located in different height, respectively. Besides, a PZT was mounted to transmit elastic waves for velocity estimation during the experiment. At first, we increased the confining pressure and then started the loading. We switched the load control method from the axial load control to the circumferential displacement one. After exceeding the peak stress, compressive stress was unloaded with a high speed and the sample was recovered. A potential fault was observed on the recovered sample surface. Waveform recording was continued throughout the test for more than 200 minutes. The result of extracting signals by an STA/LTA ratio method for the waveforms recorded by each transducer, we detected about 2,170,000 signals at the most and about 450,000 at the minimum. Recorded waveforms may also include the elastic waves from the PZT and electrical noises. To find the combination of the signals derived from the same event, we used the largest differences in travel times for all transducer pairs. Finally, we obtained about 450,000 combinations.

Selected control events and reporting odds ratio in signal detection methodology.

PubMed

Ooba, Nobuhiro; Kubota, Kiyoshi

2010-11-01

To know whether the reporting odds ratio (ROR) using "control events" can detect signals hidden behind striking reports on one or more particular events. We used data of 956 drug use investigations (DUIs) conducted between 1970 and 1998 in Japan and domestic spontaneous reports (SRs) between 1998 and 2008. The event terms in DUIs were converted to the preferred terms in Medical Dictionary for Regulatory Activities (MedDRA). We calculated the incidence proportion for various events and selected 20 "control events" with a relatively constant incidence proportion across DUIs and also reported regularly to the spontaneous reporting system. A "signal" was generated for the drug-event combination when the lower limit of 95% confidence interval of the ROR exceeded 1. We also compared the ROR in SRs with the RR in DUIs. The "control events" accounted for 18.2% of all reports. The ROR using "control events" may detect some hidden signals for a drug with the proportion of "control events" lower than the average. The median of the ratios of the ROR using "control events" to RR was around the unity indicating that "control events" roughly represented the exposure distribution though the range of the ratios was so diverse that the individual ROR might not be regarded as the estimate of RR. The use of the ROR with "control events" may give an adjunctive to the traditional signal detection methods to find a signal hidden behind some major events. Copyright © 2010 John Wiley & Sons, Ltd.

Neurotrophin signaling endosomes; biogenesis, regulation, and functions

PubMed Central

Yamashita, Naoya; Kuruvilla, Rejji

2016-01-01

In the nervous system, communication between neurons and their post-synaptic target cells is critical for the formation, refinement and maintenance of functional neuronal connections. Diffusible signals secreted by target tissues, exemplified by the family of neurotrophins, impinge on nerve terminals to influence diverse developmental events including neuronal survival and axonal growth. Key mechanisms of action of target-derived neurotrophins include the cell biological processes of endocytosis and retrograde trafficking of their Trk receptors from growth cones to cell bodies. In this review, we summarize the molecular mechanisms underlying this endosome-mediated signaling, focusing on the instructive role of neurotrophin signaling itself in directing its own trafficking. Recent studies have linked impaired neurotrophin trafficking to neurodevelopmental disorders, highlighting the relevance of neurotrophin endosomes in human health. PMID:27327126

Two Distinct Families of Protein Kinases Are Required for Plant Growth under High External Mg2+ Concentrations in Arabidopsis1

PubMed Central

Mogami, Junro; Fujita, Yasunari; Yoshida, Takuya; Tsukiori, Yoshifumi; Nakagami, Hirofumi; Nomura, Yuko; Fujiwara, Toru; Nishida, Sho; Yanagisawa, Shuichi; Ishida, Tetsuya; Takahashi, Fuminori; Morimoto, Kyoko; Kidokoro, Satoshi; Mizoi, Junya; Shinozaki, Kazuo

2015-01-01

Protein phosphorylation events play key roles in maintaining cellular ion homeostasis in higher plants, and the regulatory roles of these events in Na+ and K+ transport have been studied extensively. However, the regulatory mechanisms governing Mg2+ transport and homeostasis in higher plants remain poorly understood, despite the vital roles of Mg2+ in cellular function. A member of subclass III sucrose nonfermenting-1-related protein kinase2 (SnRK2), SRK2D/SnRK2.2, functions as a key positive regulator of abscisic acid (ABA)-mediated signaling in response to water deficit stresses in Arabidopsis (Arabidopsis thaliana). Here, we used immunoprecipitation coupled with liquid chromatography-tandem mass spectrometry analyses to identify Calcineurin B-like-interacting protein kinase26 (CIPK26) as a novel protein that physically interacts with SRK2D. In addition to CIPK26, three additional CIPKs (CIPK3, CIPK9, and CIPK23) can physically interact with SRK2D in planta. The srk2d/e/i triple mutant lacking all three members of subclass III SnRK2 and the cipk26/3/9/23 quadruple mutant lacking CIPK26, CIPK3, CIPK9, and CIPK23 showed reduced shoot growth under high external Mg2+ concentrations. Similarly, several ABA biosynthesis-deficient mutants, including aba2-1, were susceptible to high external Mg2+ concentrations. Taken together, our findings provided genetic evidence that SRK2D/E/I and CIPK26/3/9/23 are required for plant growth under high external Mg2+ concentrations in Arabidopsis. Furthermore, we showed that ABA, a key molecule in water deficit stress signaling, also serves as a signaling molecule in plant growth under high external Mg2+ concentrations. These results suggested that SRK2D/E/I- and CIPK26/3/9/23-mediated phosphorylation signaling pathways maintain cellular Mg2+ homeostasis. PMID:25614064

TERMA Framework for Biomedical Signal Analysis: An Economic-Inspired Approach.

PubMed

Elgendi, Mohamed

2016-11-02

Biomedical signals contain features that represent physiological events, and each of these events has peaks. The analysis of biomedical signals for monitoring or diagnosing diseases requires the detection of these peaks, making event detection a crucial step in biomedical signal processing. Many researchers have difficulty detecting these peaks to investigate, interpret and analyze their corresponding events. To date, there is no generic framework that captures these events in a robust, efficient and consistent manner. A new method referred to for the first time as two event-related moving averages ("TERMA") involves event-related moving averages and detects events in biomedical signals. The TERMA framework is flexible and universal and consists of six independent LEGO building bricks to achieve high accuracy detection of biomedical events. Results recommend that the window sizes for the two moving averages ( W 1 and W 2 ) have to follow the inequality ( 8 × W 1 ) ≥ W 2 ≥ ( 2 × W 1 ) . Moreover, TERMA is a simple yet efficient event detector that is suitable for wearable devices, point-of-care devices, fitness trackers and smart watches, compared to more complex machine learning solutions.

Oxidative elemental cycling under the low O2 Eoarchean atmosphere

PubMed Central

Frei, Robert; Crowe, Sean A.; Bau, Michael; Polat, Ali; Fowle, David A.; Døssing, Lasse N.

2016-01-01

The Great Oxidation Event signals the first large-scale oxygenation of the atmosphere roughly 2.4 Gyr ago. Geochemical signals diagnostic of oxidative weathering, however, extend as far back as 3.3–2.9 Gyr ago. 3.8–3.7 Gyr old rocks from Isua, Greenland stand as a deep time outpost, recording information on Earth’s earliest surface chemistry and the low oxygen primordial biosphere. Here we find fractionated Cr isotopes, relative to the igneous silicate Earth reservoir, in metamorphosed banded iron formations (BIFs) from Isua that indicate oxidative Cr cycling 3.8–3.7 Gyr ago. Elevated U/Th ratios in these BIFs relative to the contemporary crust, also signal oxidative mobilization of U. We suggest that reactive oxygen species were present in the Eoarchean surface environment, under a very low oxygen atmosphere, inducing oxidative elemental cycling during the deposition of the Isua BIFs and possibly supporting early aerobic biology. PMID:26864443

Ambient particulate matter induces IL-8 expression through an alternative NF-kB mechanism in human airway epithelial cells

EPA Science Inventory

BACKGROUND: Exposure to ambient air particulate matter (PM) has been shown to increase rates of cardio-pulmonary morbidity and mortality, but the underlying mechanisms are still not well understood. OBJECTIVE: To examine signaling events involved in the expression of the inflamma...

Accuracy-energy configurable sensor processor and IoT device for long-term activity monitoring in rare-event sensing applications.

PubMed

Park, Daejin; Cho, Jeonghun

2014-01-01

A specially designed sensor processor used as a main processor in IoT (internet-of-thing) device for the rare-event sensing applications is proposed. The IoT device including the proposed sensor processor performs the event-driven sensor data processing based on an accuracy-energy configurable event-quantization in architectural level. The received sensor signal is converted into a sequence of atomic events, which is extracted by the signal-to-atomic-event generator (AEG). Using an event signal processing unit (EPU) as an accelerator, the extracted atomic events are analyzed to build the final event. Instead of the sampled raw data transmission via internet, the proposed method delays the communication with a host system until a semantic pattern of the signal is identified as a final event. The proposed processor is implemented on a single chip, which is tightly coupled in bus connection level with a microcontroller using a 0.18 μm CMOS embedded-flash process. For experimental results, we evaluated the proposed sensor processor by using an IR- (infrared radio-) based signal reflection and sensor signal acquisition system. We successfully demonstrated that the expected power consumption is in the range of 20% to 50% compared to the result of the basement in case of allowing 10% accuracy error.

Event Rate for LISA Gravitational Wave Signals from Black Hole-Massive Black Hole Coalescences

NASA Technical Reports Server (NTRS)

Bender, Peter L.; Salamon, Michael H. (Technical Monitor)

2002-01-01

Earlier work under a previous grant had been mainly on investigating the event rate for coalescences of white dwarfs or neutron stars with massive black holes (MBHs) in galactic nuclei. Under the new grant, two studies were undertaken. One was an approximate extension of the earlier study to stellar mass black holes as the lighter object, with masses in the range of roughly 3 to 20 M_sun, rather than about 1 M_sun. The other was an improved estimate of the confusion noise due to galactic binaries against which the signals from BH-MDH coalescences would have to be detected. In the earlier work, the mass of the white dwarfs (WDs) and neutron stars (NSs) was assumed to be about the same as that of the unevolved stars in the density cusp around the galactic center MBH. However, with the BH mass being substantially larger, the sinking down of BHs toward the center (mass segregation) became important and was included in the model. A single representative mass of 7 M_sun was used.

Positron emission tomography wrist detector

DOEpatents

Schlyer, David J.; O'Connor, Paul; Woody, Craig; Junnarkar, Sachin Shrirang; Radeka, Veljko; Vaska, Paul; Pratte, Jean-Francois

2006-08-15

A method of serially transferring annihilation information in a compact positron emission tomography (PET) scanner includes generating a time signal representing a time-of-occurrence of an annihilation event, generating an address signal representing a channel detecting the annihilation event, and generating a channel signal including the time and address signals. The method also includes generating a composite signal including the channel signal and another similarly generated channel signal concerning another annihilation event. An apparatus that serially transfers annihilation information includes a time signal generator, address signal generator, channel signal generator, and composite signal generator. The time signal is asynchronous and the address signal is synchronous to a clock signal. A PET scanner includes a scintillation array, detection array, front-end array, and a serial encoder. The serial encoders include the time signal generator, address signal generator, channel signal generator, and composite signal generator.

E4orf1 induction in adipose tissue promotes insulin-independent signaling in the adipocyte.

PubMed

Kusminski, Christine M; Gallardo-Montejano, Violeta I; Wang, Zhao V; Hegde, Vijay; Bickel, Perry E; Dhurandhar, Nikhil V; Scherer, Philipp E

2015-10-01

Type 2 diabetes remains a worldwide epidemic with major pathophysiological changes as a result of chronic insulin resistance. Insulin regulates numerous biochemical pathways related to carbohydrate and lipid metabolism. We have generated a novel mouse model that allows us to constitutively activate, in an inducible fashion, the distal branch of the insulin signaling transduction pathway specifically in adipocytes. Using the adenoviral 36 E4orf1 protein, we chronically stimulate locally the Ras-ERK-MAPK signaling pathway. At the whole body level, this leads to reduced body-weight gain under a high fat diet challenge. Despite overlapping glucose tolerance curves, there is a reduced requirement for insulin action under these conditions. The mice further exhibit reduced circulating adiponectin levels that ultimately lead to impaired lipid clearance, and inflamed and fibrotic white adipose tissues. Nevertheless, they are protected from diet-induced hepatic steatosis. As we observe constitutively elevated p-Akt levels in the adipocytes, even under conditions of low insulin levels, this pinpoints enhanced Ras-ERK-MAPK signaling in transgenic adipocytes as a potential alternative route to bypass proximal insulin signaling events. We conclude that E4orf1 expression in the adipocyte leads to enhanced baseline activation of the distal insulin signaling node, yet impaired insulin receptor stimulation in the presence of insulin, with important implications for the regulation of adiponectin secretion. The resulting systemic phenotype is complex, yet highlights the powerful nature of manipulating selective branches of the insulin signaling network within the adipocyte.

Automatic event detection in low SNR microseismic signals based on multi-scale permutation entropy and a support vector machine

NASA Astrophysics Data System (ADS)

Jia, Rui-Sheng; Sun, Hong-Mei; Peng, Yan-Jun; Liang, Yong-Quan; Lu, Xin-Ming

2017-07-01

Microseismic monitoring is an effective means for providing early warning of rock or coal dynamical disasters, and its first step is microseismic event detection, although low SNR microseismic signals often cannot effectively be detected by routine methods. To solve this problem, this paper presents permutation entropy and a support vector machine to detect low SNR microseismic events. First, an extraction method of signal features based on multi-scale permutation entropy is proposed by studying the influence of the scale factor on the signal permutation entropy. Second, the detection model of low SNR microseismic events based on the least squares support vector machine is built by performing a multi-scale permutation entropy calculation for the collected vibration signals, constructing a feature vector set of signals. Finally, a comparative analysis of the microseismic events and noise signals in the experiment proves that the different characteristics of the two can be fully expressed by using multi-scale permutation entropy. The detection model of microseismic events combined with the support vector machine, which has the features of high classification accuracy and fast real-time algorithms, can meet the requirements of online, real-time extractions of microseismic events.

Hippocampal Processing of Ambiguity Enhances Fear Memory

PubMed Central

Amadi, Ugwechi; Lim, Seh Hong; Liu, Elizabeth; Baratta, Michael V.; Goosens, Ki Ann

2016-01-01

Despite the ubiquitous use of Pavlovian fear conditioning as a model for fear learning, the highly predictable conditions used in the laboratory do not resemble real-world conditions, where dangerous situations can lead to unpleasant outcomes in unpredictable ways. Here we varied the timing of aversive events following predictive cues in rodents and discovered that temporal ambiguity of aversive events greatly enhances fear. During fear conditioning with unpredictably timed aversive events, pharmacological inactivation of the dorsal hippocampus or optogenetic silencing of CA1 cells during aversive negative prediction errors prevented this enhancement of fear without impacting fear learning for predictable events. Dorsal hippocampal inactivation also prevented ambiguity-related enhancement of fear during auditory fear conditioning under a partial reinforcement schedule. These results reveal that information about the timing and occurrence of aversive events is rapidly acquired and that unexpectedly timed or omitted aversive events generate hippocampal signals to enhance fear learning. PMID:28182526

Hippocampal Processing of Ambiguity Enhances Fear Memory.

PubMed

Amadi, Ugwechi; Lim, Seh Hong; Liu, Elizabeth; Baratta, Michael V; Goosens, Ki A

2017-02-01

Despite the ubiquitous use of Pavlovian fear conditioning as a model for fear learning, the highly predictable conditions used in the laboratory do not resemble real-world conditions, in which dangerous situations can lead to unpleasant outcomes in unpredictable ways. In the current experiments, we varied the timing of aversive events after predictive cues in rodents and discovered that temporal ambiguity of aversive events greatly enhances fear. During fear conditioning with unpredictably timed aversive events, pharmacological inactivation of the dorsal hippocampus or optogenetic silencing of cornu ammonis 1 cells during aversive negative prediction errors prevented this enhancement of fear without affecting fear learning for predictable events. Dorsal hippocampal inactivation also prevented ambiguity-related enhancement of fear during auditory fear conditioning under a partial-reinforcement schedule. These results reveal that information about the timing and occurrence of aversive events is rapidly acquired and that unexpectedly timed or omitted aversive events generate hippocampal signals to enhance fear learning.

On comprehensive recovery of an aftershock sequence with cross correlation

NASA Astrophysics Data System (ADS)

Kitov, I.; Bobrov, D.; Coyne, J.; Turyomurugyendo, G.

2012-04-01

We have introduced cross correlation between seismic waveforms as a technique for signal detection and automatic event building at the International Data Centre (IDC) of the Comprehensive Nuclear-Test-Ban Treaty Organization. The intuition behind signal detection is simple - small and mid-sized seismic events close in space should produce similar signals at the same seismic stations. Equivalently, these signals have to be characterized by a high cross correlation coefficient. For array stations with many individual sensors distributed over a large area, signals from events at distances beyond, say, 50 km, are subject to destructive interference when cross correlated due to changing time delays between various channels. Thus, any cross correlation coefficient above some predefined threshold can be considered as a signature of a valid signal. With a dense grid of master events (spacing between adjacent masters between 20 km and 50 km corresponds to the statistically estimated correlation distance) with high quality (signal-to-noise ratio above 10) template waveforms at primary array stations of the International Monitoring System one can detect signals from and then build natural and manmade seismic events close to the master ones. The use of cross correlation allows detecting smaller signals (sometimes below noise level) than provided by the current IDC detecting techniques. As a result it is possible to automatically build from 50% to 100% more valid seismic events than included in the Reviewed Event Bulletin (REB). We have developed a tentative pipeline for automatic processing at the IDC. It includes three major stages. Firstly, we calculate cross correlation coefficient for a given master and continuous waveforms at the same stations and carry out signal detection as based on the statistical behavior of signal-to-noise ratio of the cross correlation coefficient. Secondly, a thorough screening is performed for all obtained signals using f-k analysis and F-statistics as applied to the cross-correlation traces at individual channels of all included array stations. Thirdly, local (i.e. confined to the correlation distance around the master event) association of origin times of all qualified signals is fulfilled. These origin times are calculated from the arrival times of these signals, which are reduced to the origin times by the travel times from the master event. An aftershock sequence of a mid-size earthquake is an ideal case to test cross correlation techniques for autiomatic event building. All events should be close to the mainshock and occur within several days. Here we analyse the aftershock sequence of an earthquake in the North Atlantic Ocean with mb(IDC)=4.79. The REB includes 38 events at distances less than 150 km from the mainshock. Our ultimate goal is to excersice the complete iterative procedure to find all possible aftershocks. We start with the mainshock and recover ten aftershocks with the largest number of stations to produce an initial set of master events with the highest quality templates. Then we find all aftershocks in the REB and many additional events, which were not originally found by the IDC. Using all events found after the first iteration as master events we find new events, which are also used in the next iteration. The iterative process stops when no new events can be found. In that sense the final set of aftershocks obtained with cross correlation is a comprehensive one.

More on molecular excitations: Dark matter detection in ice

DOE PAGES

Va'vra, J.

2016-08-10

In this paper we investigate di-atomic molecules embedded in ice crystals under strain. In this environment coherent vibrations of many OH-bonds may be generated by one WIMP collision. The detection of such multiple-photon signals may provide a signature of a 100 GeV/c 2 WIMP. To do a proper lab test of “WIMP-induced” multi-photon emission is very difficult. As a result, we suggest that Ice Cube make a search for multi-photon events, and investigate whether the rate of such events exhibits yearly modulation.

Evaluating the event-related synchronization and desynchronization by means of a statistical frequency test.

PubMed

Miranda de Sá, Antonio Mauricio F L; Infantosi, Antonio Fernando C; Lazarev, Vladimir V

2007-01-01

In the present work, a commonly used index for evaluating the Event-Related Synchronization and Desynchronization (ERS/ERD) in the EEG was expressed as a function of the Spectral F-Test (SFT), which is a statistical test for assessing if two sample spectra are from populations with identical theoretical spectra. The sampling distribution of SFT has been derived, allowing hence ERS/ERD to be evaluated under a statistical basis. An example of the technique was also provided in the EEG signals from 10 normal subjects during intermittent photic stimulation.

Quantitative measures for redox signaling.

PubMed

Pillay, Ché S; Eagling, Beatrice D; Driscoll, Scott R E; Rohwer, Johann M

2016-07-01

Redox signaling is now recognized as an important regulatory mechanism for a number of cellular processes including the antioxidant response, phosphokinase signal transduction and redox metabolism. While there has been considerable progress in identifying the cellular machinery involved in redox signaling, quantitative measures of redox signals have been lacking, limiting efforts aimed at understanding and comparing redox signaling under normoxic and pathogenic conditions. Here we have outlined some of the accepted principles for redox signaling, including the description of hydrogen peroxide as a signaling molecule and the role of kinetics in conferring specificity to these signaling events. Based on these principles, we then develop a working definition for redox signaling and review a number of quantitative methods that have been employed to describe signaling in other systems. Using computational modeling and published data, we show how time- and concentration- dependent analyses, in particular, could be used to quantitatively describe redox signaling and therefore provide important insights into the functional organization of redox networks. Finally, we consider some of the key challenges with implementing these methods. Copyright © 2016 Elsevier Inc. All rights reserved.

An energy ratio feature extraction method for optical fiber vibration signal

NASA Astrophysics Data System (ADS)

Sheng, Zhiyong; Zhang, Xinyan; Wang, Yanping; Hou, Weiming; Yang, Dan

2018-03-01

The intrusion events in the optical fiber pre-warning system (OFPS) are divided into two types which are harmful intrusion event and harmless interference event. At present, the signal feature extraction methods of these two types of events are usually designed from the view of the time domain. However, the differences of time-domain characteristics for different harmful intrusion events are not obvious, which cannot reflect the diversity of them in detail. We find that the spectrum distribution of different intrusion signals has obvious differences. For this reason, the intrusion signal is transformed into the frequency domain. In this paper, an energy ratio feature extraction method of harmful intrusion event is drawn on. Firstly, the intrusion signals are pre-processed and the power spectral density (PSD) is calculated. Then, the energy ratio of different frequency bands is calculated, and the corresponding feature vector of each type of intrusion event is further formed. The linear discriminant analysis (LDA) classifier is used to identify the harmful intrusion events in the paper. Experimental results show that the algorithm improves the recognition rate of the intrusion signal, and further verifies the feasibility and validity of the algorithm.

Tree mortality in the eastern Mediterranean, causes and implications under climatic change

NASA Astrophysics Data System (ADS)

Sarris, Dimitrios; Iacovou, Valentina; Hoch, Guenter; Vennetier, Michel; Siegwolf, Rolf; Christodoulakis, Dimitrios; Koerner, Christian

2015-04-01

The eastern Mediterranean has experienced repeated incidents of forest mortality related to drought in recent decades. Such events may become more frequent in the future as drought conditions are projected to further intensify due to global warming. We have been investigating the causes behind such forest mortality events in Pinus halepensis, (the most drought tolerant pine in the Mediterranean). We cored tree stems and sampled various tissue types from dry habitats close to sea level and explored growth responses, stable isotope signals and non-structural carbohydrate (NSC) concentrations. Under intense drought that coincided with pine desiccation events in natural populations our result indicate a significant reduction in tree growth, the most significant in more than a century despite the increase in atmospheric CO2 concentrations in recent decades. This has been accompanied by a lengthening in the integration periods of rainfall needed for pine growth, reaching even 5-6 years before and including the year of mortality occurrence. Oxygen stable isotopes indicate that these signals were associated with a shift in tree water utilization from deeper moisture pools related to past rainfall events. Furthermore, where the driest conditions occur, pine carbon reserves were found to increase in stem tissue, indicating that mortality in these pines cannot be explained by carbon starvation. Our findings suggest that for pine populations that are already water limited (i) a further atmospheric CO2 increase will not compensate for the reduction in growth because of a drier climate, (ii) hydraulic failure appears as the most likely cause of pine desiccation, as no shortage occurs in tree carbon reserves, (iii) a further increase in mortality events may cause these systems to become carbon sources.

Vibration response of spalled rolling element bearings: Observations, simulations and signal processing techniques to track the spall size

NASA Astrophysics Data System (ADS)

Sawalhi, N.; Randall, R. B.

2011-04-01

Fatigue in rolling element bearings, resulting in spalling of the races and/or rolling elements, is the most common cause of bearing failure. The useful life of the bearing may extend considerably beyond the appearance of the first spall and a premature removal of the bearing from service can be very expensive, but on the other hand chances cannot be taken with safety of machines or personnel. Previous studies indicated that there might be two parts to the defect vibration signal of a spalled bearing, the first part being originating from the entry of the rolling element into the fault (de-stress) and the second part being due to the departure of the rolling element from the fault (re-stress). This is investigated in this paper using vibration signatures of seeded faults at different speeds. The acceleration signals resulting from the entry of the rolling element into the spall and exit from it were found to be of different natures. The entry into the fault can be described as a step response, with mainly low frequency content, while the impact excites a much broader frequency impulse response. The latter is the most noticeable and prominent event, especially when examining the high pass filtered response or the enveloped signal. In order to enable a clear separation of the two events, and produce an averaged estimate of the size of the fault, two approaches are proposed to enhance the entry event while keeping the impulse response. The first approach (joint treatment) utilizes pre-whitening to balance the low and high frequency energy, then octave band wavelet analysis to allow selection of the best band (or scale) to balance the two pulses with similar frequency content. In the second approach, a separate treatment is applied to the step and the impulse responses, so that they can be equally represented in the signal. Cepstrum analysis can be used to give an average estimate of the spacing between the entry and impact events, but the latter can also be assessed by an arithmetic estimation of the mean and standard deviation of the event separation for a number of realizations, in particular for the second approach. In order to determine the effects of various simulations and signal processing parameters on the estimated delay times, the entry and exit events were simulated as modified step and impulse responses with precisely known starting times. The simulation was also found useful in pointing to artefacts associated with the cepstrum calculation, which affect even the simulated signals, and have thus prompted modifications of the processing of real signals. The results presented for the two approaches give a reasonable approximation of the measured fault widths (double the spacing between the entry and impact events) under different speed conditions, but the method of separate treatment is somewhat better and is thus recommended.

Temporal-Spatial Interaction between Reactive Oxygen Species and Abscisic Acid Regulates Rapid Systemic Acclimation in Plants[W][OPEN

PubMed Central

Suzuki, Nobuhiro; Miller, Gad; Salazar, Carolina; Mondal, Hossain A.; Shulaev, Elena; Cortes, Diego F.; Shuman, Joel L.; Luo, Xiaozhong; Shah, Jyoti; Schlauch, Karen; Shulaev, Vladimir; Mittler, Ron

2013-01-01

Being sessile organisms, plants evolved sophisticated acclimation mechanisms to cope with abiotic challenges in their environment. These are activated at the initial site of exposure to stress, as well as in systemic tissues that have not been subjected to stress (termed systemic acquired acclimation [SAA]). Although SAA is thought to play a key role in plant survival during stress, little is known about the signaling mechanisms underlying it. Here, we report that SAA in plants requires at least two different signals: an autopropagating wave of reactive oxygen species (ROS) that rapidly spreads from the initial site of exposure to the entire plant and a stress-specific signal that conveys abiotic stress specificity. We further demonstrate that SAA is stress specific and that a temporal–spatial interaction between ROS and abscisic acid regulates rapid SAA to heat stress in plants. In addition, we demonstrate that the rapid ROS signal is associated with the propagation of electric signals in Arabidopsis thaliana. Our findings unravel some of the basic signaling mechanisms underlying SAA in plants and reveal that signaling events and transcriptome and metabolome reprogramming of systemic tissues in response to abiotic stress occur at a much faster rate than previously envisioned. PMID:24038652

Phosphorylation of Ribosomal Protein RPS6 Integrates Light Signals and Circadian Clock Signals

DOE PAGES

Enganti, Ramya; Cho, Sung Ki; Toperzer, Jody D.; ...

2018-01-19

The translation of mRNA into protein is tightly regulated by the light environment as well as by the circadian clock. Although changes in translational efficiency have been well documented at the level of mRNA-ribosome loading, the underlying mechanisms are unclear. The reversible phosphorylation of RIBOSOMAL PROTEIN OF THE SMALL SUBUNIT 6 (RPS6) has been known for 40 years, but the biochemical significance of this event remains unclear to this day. Here, we confirm using a clock-deficient strain of Arabidopsis thaliana that RPS6 phosphorylation (RPS6-P) is controlled by the diel light-dark cycle with a peak during the day. Strikingly, when wild-type,more » clock-enabled, seedlings that have been entrained to a light-dark cycle are placed under free-running conditions, the circadian clock drives a cycle of RPS6-P with an opposite phase, peaking during the subjective night. We show that in wild-type seedlings under a light-dark cycle, the incoherent light and clock signals are integrated by the plant to cause an oscillation in RPS6-P with a reduced amplitude with a peak during the day. Sucrose can stimulate RPS6-P, as seen when sucrose in the medium masks the light response of etiolated seedlings. However, the diel cycles of RPS6-P are observed in the presence of 1% sucrose and in its absence. Sucrose at a high concentration of 3% appears to interfere with the robust integration of light and clock signals at the level of RPS6-P. Finally, we addressed whether RPS6-P occurs uniformly in polysomes, non-polysomal ribosomes and their subunits, and non-ribosomal protein. It is the polysomal RPS6 whose phosphorylation is most highly stimulated by light and repressed by darkness. These data exemplify a striking case of contrasting biochemical regulation between clock signals and light signals. Although the physiological significance of RPS6-P remains unknown, our data provide a mechanistic basis for the future understanding of this enigmatic event.« less

Phosphorylation of Ribosomal Protein RPS6 Integrates Light Signals and Circadian Clock Signals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Enganti, Ramya; Cho, Sung Ki; Toperzer, Jody D.

The translation of mRNA into protein is tightly regulated by the light environment as well as by the circadian clock. Although changes in translational efficiency have been well documented at the level of mRNA-ribosome loading, the underlying mechanisms are unclear. The reversible phosphorylation of RIBOSOMAL PROTEIN OF THE SMALL SUBUNIT 6 (RPS6) has been known for 40 years, but the biochemical significance of this event remains unclear to this day. Here, we confirm using a clock-deficient strain of Arabidopsis thaliana that RPS6 phosphorylation (RPS6-P) is controlled by the diel light-dark cycle with a peak during the day. Strikingly, when wild-type,more » clock-enabled, seedlings that have been entrained to a light-dark cycle are placed under free-running conditions, the circadian clock drives a cycle of RPS6-P with an opposite phase, peaking during the subjective night. We show that in wild-type seedlings under a light-dark cycle, the incoherent light and clock signals are integrated by the plant to cause an oscillation in RPS6-P with a reduced amplitude with a peak during the day. Sucrose can stimulate RPS6-P, as seen when sucrose in the medium masks the light response of etiolated seedlings. However, the diel cycles of RPS6-P are observed in the presence of 1% sucrose and in its absence. Sucrose at a high concentration of 3% appears to interfere with the robust integration of light and clock signals at the level of RPS6-P. Finally, we addressed whether RPS6-P occurs uniformly in polysomes, non-polysomal ribosomes and their subunits, and non-ribosomal protein. It is the polysomal RPS6 whose phosphorylation is most highly stimulated by light and repressed by darkness. These data exemplify a striking case of contrasting biochemical regulation between clock signals and light signals. Although the physiological significance of RPS6-P remains unknown, our data provide a mechanistic basis for the future understanding of this enigmatic event.« less

Understanding the rapidity of subsurface storm flow response from a fracture-oriented shallow vadose through a new perspective

NASA Astrophysics Data System (ADS)

Zhao, Peng; Zhao, Pei; Liang, Chuan; Li, Tianyang; Zhou, Baojia

2017-01-01

Velocity and celerity in hydrologic systems are controlled by different mechanisms. Efforts were made through joint sample collection and the use of hydrographs and tracers to understand the rapidity of the subsurface flow response to rainstorms on hourly time scales. Three deep subsurface flows during four natural rainstorm events were monitored. The results show that (1) deeper discharge was observed early in responding rainfall events and yielded a high hydrograph amplitude; (2) a ratio index, k, reflecting the dynamic change of the rainfall perturbation intensity in subsurface flow, might reveal inner causal relationships between the flow index and the tracer signal index. Most values of k were larger than 1 at the perturbation stage but approximated 1 at the no-perturbation stage; and (3) for statistical analysis of tracer signals in subsurface flows, the total standard deviation was 17.2, 11.9, 7.4 and 3.5 at perturbation stages and 4.4, 2.5, 1.1, and 0.95 at the non-perturbation stage for observed events. These events were 3-7 times higher in the former rather than the later, reflecting that the variation of tracer signals primarily occurred under rainfall perturbation. Thus, we affirmed that the dynamic features of rainfall have a key effect on rapid processes because, besides the gravity, mechanical waves originating from dynamic rainfall features are another driving factor for conversion between different types of rainfall mechanical energy. A conceptual model for pressure wave propagation was proposed, in which virtual subsurface flow processes in a heterogeneous vadose zone under rainfall are analogous to the water hammer phenomenon in complex conduit systems. Such an analogy can allow pressure in a shallow vadose to increase and decrease and directly influence the velocity and celerity of the flow reflecting a mechanism for rapid subsurface hydrologic response processes in the shallow vadose zone.

Music 4C, a multi-voiced synthesis program with instruments defined in C

NASA Astrophysics Data System (ADS)

Beauchamp, James W.

2003-04-01

Music 4C is a program which runs under Unix (including Linux) and provides a means for the synthesis of arbitrary signals as defined by the C code. The program is actually a loose translation of an earlier program, Music 4BF [H. S. Howe, Jr., Electronic Music Synthesis (Norton, 1975)]. A set of instrument definitions are driven by a numerical score which consists of a series of ``events.'' Each event gives an instrument name, start time and duration, and a number of parameters (e.g., pitch) which describe the event. Each instrument definition consists of event parameters, performance variables, initializations, and a synthesis algorithmic code. Thus, the synthetic signal, no matter how complex, is precisely defined. Moreover, the resulting sounds can be overlaid in any arbitrary pattern. The program serves as a mixer of algorithmically produced sounds or recorded sounds taken from sample files or synthesized from spectrum files. A score file can be entered by hand, generated from a program, translated from a MIDI file, or generated from an alpha-numeric score using an auxiliary program, Notepro. Output sample files are in wav, snd, or aiff format. The program is provided in the C source code for download.

Unsupervised EEG analysis for automated epileptic seizure detection

NASA Astrophysics Data System (ADS)

Birjandtalab, Javad; Pouyan, Maziyar Baran; Nourani, Mehrdad

2016-07-01

Epilepsy is a neurological disorder which can, if not controlled, potentially cause unexpected death. It is extremely crucial to have accurate automatic pattern recognition and data mining techniques to detect the onset of seizures and inform care-givers to help the patients. EEG signals are the preferred biosignals for diagnosis of epileptic patients. Most of the existing pattern recognition techniques used in EEG analysis leverage the notion of supervised machine learning algorithms. Since seizure data are heavily under-represented, such techniques are not always practical particularly when the labeled data is not sufficiently available or when disease progression is rapid and the corresponding EEG footprint pattern will not be robust. Furthermore, EEG pattern change is highly individual dependent and requires experienced specialists to annotate the seizure and non-seizure events. In this work, we present an unsupervised technique to discriminate seizures and non-seizures events. We employ power spectral density of EEG signals in different frequency bands that are informative features to accurately cluster seizure and non-seizure events. The experimental results tried so far indicate achieving more than 90% accuracy in clustering seizure and non-seizure events without having any prior knowledge on patient's history.

PH motifs in PAR1&2 endow breast cancer growth.

PubMed

Kancharla, A; Maoz, M; Jaber, M; Agranovich, D; Peretz, T; Grisaru-Granovsky, S; Uziely, B; Bar-Shavit, R

2015-11-24

Although emerging roles of protease-activated receptor1&2 (PAR1&2) in cancer are recognized, their underlying signalling events are poorly understood. Here we show signal-binding motifs in PAR1&2 that are critical for breast cancer growth. This occurs via the association of the pleckstrin homology (PH) domain with Akt/PKB as a key signalling event of PARs. Other PH-domain signal-proteins such as Etk/Bmx and Vav3 also associate with PAR1 and PAR2 through their PH domains. PAR1 and PAR2 bind with priority to Etk/Bmx. A point mutation in PAR2, H349A, but not in R352A, abrogates PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumour growth in vivo and placental extravillous trophoblast (EVT) invasion in vitro. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind the PH domain, reduces mammary tumours and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes.

Search for a standard model Higgs boson produced in association with a top-quark pair and decaying to bottom quarks using a matrix element method

DOE PAGES

Khachatryan, Vardan

2015-06-09

A search for a standard model Higgs boson produced in association with a top-quark pair and decaying to bottom quarks is presented. Events with hadronic jets and one or two oppositely charged leptons are selected from a data sample corresponding to an integrated luminosity of 19.5fb -1 collected by the CMS experiment at the LHC in pp collisions at a centre-of-mass energy of 8TeV. In order to separate the signal from the larger tt¯ + jets background, this analysis uses a matrix element method that assigns a probability density value to each reconstructed event under signal or background hypotheses. Themore » ratio between the two values is used in a maximum likelihood fit to extract the signal yield. The results are presented in terms of the measured signal strength modifier, μ, relative to the standard model prediction for a Higgs boson mass of 125GeV. The observed (expected) exclusion limit at a 95 % confidence level is μ < 4.2 (3.3), corresponding to a best fit value μ^ = 1.2 +1.6 -1.5.« less

Search for a standard model Higgs boson produced in association with a top-quark pair and decaying to bottom quarks using a matrix element method.

PubMed

Khachatryan, V; Sirunyan, A M; Tumasyan, A; Adam, W; Bergauer, T; Dragicevic, M; Erö, J; Friedl, M; Frühwirth, R; Ghete, V M; Hartl, C; Hörmann, N; Hrubec, J; Jeitler, M; Kiesenhofer, W; Knünz, V; Krammer, M; Krätschmer, I; Liko, D; Mikulec, I; Rabady, D; Rahbaran, B; Rohringer, H; Schöfbeck, R; Strauss, J; Treberer-Treberspurg, W; Waltenberger, W; Wulz, C-E; Mossolov, V; Shumeiko, N; Suarez Gonzalez, J; Alderweireldt, S; Bansal, S; Cornelis, T; De Wolf, E A; Janssen, X; Knutsson, A; Lauwers, J; Luyckx, S; Ochesanu, S; Rougny, R; Van De Klundert, M; Van Haevermaet, H; Van Mechelen, P; Van Remortel, N; Van Spilbeeck, A; Blekman, F; Blyweert, S; D'Hondt, J; Daci, N; Heracleous, N; Keaveney, J; Lowette, S; Maes, M; Olbrechts, A; Python, Q; Strom, D; Tavernier, S; Van Doninck, W; Van Mulders, P; Van Onsem, G P; Villella, I; Caillol, C; Clerbaux, B; De Lentdecker, G; Dobur, D; Favart, L; Gay, A P R; Grebenyuk, A; Léonard, A; Mohammadi, A; Perniè, L; Randle-Conde, A; Reis, T; Seva, T; Thomas, L; Vander Velde, C; Vanlaer, P; Wang, J; Zenoni, F; Adler, V; Beernaert, K; Benucci, L; Cimmino, A; Costantini, S; Crucy, S; Fagot, A; Garcia, G; Mccartin, J; Ocampo Rios, A A; Poyraz, D; Ryckbosch, D; Salva Diblen, S; Sigamani, M; Strobbe, N; Thyssen, F; Tytgat, M; Yazgan, E; Zaganidis, N; Basegmez, S; Beluffi, C; Bruno, G; Castello, R; Caudron, A; Ceard, L; Da Silveira, G G; Delaere, C; du Pree, T; Favart, D; Forthomme, L; Giammanco, A; Hollar, J; Jafari, A; Jez, P; Komm, M; Lemaitre, V; Nuttens, C; Pagano, D; Perrini, L; Pin, A; Piotrzkowski, K; Popov, A; Quertenmont, L; Selvaggi, M; Vidal Marono, M; Vizan Garcia, J M; Beliy, N; Caebergs, T; Daubie, E; Hammad, G H; Júnior, W L Aldá; Alves, G A; Brito, L; Correa Martins Junior, M; Martins, T Dos Reis; Molina, J; Mora Herrera, C; Pol, M E; Rebello Teles, P; Carvalho, W; Chinellato, J; Custódio, A; Da Costa, E M; De Jesus Damiao, D; De Oliveira Martins, C; Fonseca De Souza, S; Malbouisson, H; Matos Figueiredo, D; Mundim, L; Nogima, H; Prado Da Silva, W L; Santaolalla, J; Santoro, A; Sznajder, A; Tonelli Manganote, E J; Vilela Pereira, A; Bernardes, C A; Dogra, S; Fernandez Perez Tomei, T R; Gregores, E M; Mercadante, P G; Novaes, S F; Padula, Sandra S; Aleksandrov, A; Genchev, V; Hadjiiska, R; Iaydjiev, P; Marinov, A; Piperov, S; Rodozov, M; Stoykova, S; Sultanov, G; Vutova, M; Dimitrov, A; Glushkov, I; Litov, L; Pavlov, B; Petkov, P; Bian, J G; Chen, G M; Chen, H S; Chen, M; Cheng, T; Du, R; Jiang, C H; Plestina, R; Romeo, F; Tao, J; Wang, Z; Asawatangtrakuldee, C; Ban, Y; Liu, S; Mao, Y; Qian, S J; Wang, D; Xu, Z; Zhang, F; Zhang, L; Zou, W; Avila, C; Cabrera, A; Chaparro Sierra, L F; Florez, C; Gomez, J P; Gomez Moreno, B; Sanabria, J C; Godinovic, N; Lelas, D; Polic, D; Puljak, I; Antunovic, Z; Kovac, M; Brigljevic, V; Kadija, K; Luetic, J; Mekterovic, D; Sudic, L; Attikis, A; Mavromanolakis, G; Mousa, J; Nicolaou, C; Ptochos, F; Razis, P A; Rykaczewski, H; Bodlak, M; Finger, M; Finger, M; Assran, Y; Ellithi Kamel, A; Mahmoud, M A; Radi, A; Kadastik, M; Murumaa, M; Raidal, M; Tiko, A; Eerola, P; Voutilainen, M; Härkönen, J; Karimäki, V; Kinnunen, R; Lampén, T; Lassila-Perini, K; Lehti, S; Lindén, T; Luukka, P; Mäenpää, T; Peltola, T; Tuominen, E; Tuominiemi, J; Tuovinen, E; Wendland, L; Talvitie, J; Tuuva, T; Besancon, M; Couderc, F; Dejardin, M; Denegri, D; Fabbro, B; Faure, J L; Favaro, C; Ferri, F; Ganjour, S; Givernaud, A; Gras, P; Hamel de Monchenault, G; Jarry, P; Locci, E; Malcles, J; Rander, J; Rosowsky, A; Titov, M; Baffioni, S; Beaudette, F; Busson, P; Chapon, E; Charlot, C; Dahms, T; Dobrzynski, L; Filipovic, N; Florent, A; Granier de Cassagnac, R; Mastrolorenzo, L; Miné, P; Naranjo, I N; Nguyen, M; Ochando, C; Ortona, G; Paganini, P; Regnard, S; Salerno, R; Sauvan, J B; Sirois, Y; Veelken, C; Yilmaz, Y; Zabi, A; Agram, J-L; Andrea, J; Aubin, A; Bloch, D; Brom, J-M; Chabert, E C; Chanon, N; Collard, C; Conte, E; Fontaine, J-C; Gelé, D; Goerlach, U; Goetzmann, C; Le Bihan, A-C; Skovpen, K; Van Hove, P; Gadrat, S; Beauceron, S; Beaupere, N; Bernet, C; Boudoul, G; Bouvier, E; Brochet, S; Carrillo Montoya, C A; Chasserat, J; Chierici, R; Contardo, D; Courbon, B; Depasse, P; El Mamouni, H; Fan, J; Fay, J; Gascon, S; Gouzevitch, M; Ille, B; Kurca, T; Lethuillier, M; Mirabito, L; Pequegnot, A L; Perries, S; Ruiz Alvarez, J D; Sabes, D; Sgandurra, L; Sordini, V; Vander Donckt, M; Verdier, P; Viret, S; Xiao, H; Tsamalaidze, Z; Autermann, C; Beranek, S; Bontenackels, M; Edelhoff, M; Feld, L; Heister, A; Klein, K; Lipinski, M; Ostapchuk, A; Preuten, M; Raupach, F; Sammet, J; Schael, S; Schulte, J F; Weber, H; Wittmer, B; Zhukov, V; Ata, M; Brodski, M; Dietz-Laursonn, E; Duchardt, D; Erdmann, M; Fischer, R; Güth, A; Hebbeker, T; Heidemann, C; Hoepfner, K; Klingebiel, D; Knutzen, S; Kreuzer, P; Merschmeyer, M; Meyer, A; Mittag, G; Millet, P; Olschewski, M; Padeken, K; Papacz, P; Reithler, H; Schmitz, S A; Sonnenschein, L; Teyssier, D; Thüer, S; Cherepanov, V; Erdogan, Y; Flügge, G; Geenen, H; Geisler, M; Haj Ahmad, W; Hoehle, F; Kargoll, B; Kress, T; Kuessel, Y; Künsken, A; Lingemann, J; Nowack, A; Nugent, I M; Pistone, C; Pooth, O; Stahl, A; Aldaya Martin, M; Asin, I; Bartosik, N; Behr, J; Behrens, U; Bell, A J; Bethani, A; Borras, K; Burgmeier, A; Cakir, A; Calligaris, L; Campbell, A; Choudhury, S; Costanza, F; Diez Pardos, C; Dolinska, G; Dooling, S; Dorland, T; Eckerlin, G; Eckstein, D; Eichhorn, T; Flucke, G; Garcia, J Garay; Geiser, A; Gizhko, A; Gunnellini, P; Hauk, J; Hempel, M; Jung, H; Kalogeropoulos, A; Karacheban, O; Kasemann, M; Katsas, P; Kieseler, J; Kleinwort, C; Korol, I; Krücker, D; Lange, W; Leonard, J; Lipka, K; Lobanov, A; Lohmann, W; Lutz, B; Mankel, R; Marfin, I; Melzer-Pellmann, I-A; Meyer, A B; Mnich, J; Mussgiller, A; Naumann-Emme, S; Nayak, A; Ntomari, E; Perrey, H; Pitzl, D; Placakyte, R; Raspereza, A; Ribeiro Cipriano, P M; Roland, B; Ron, E; Sahin, M Ö; Salfeld-Nebgen, J; Saxena, P; Schoerner-Sadenius, T; Schröder, M; Seitz, C; Spannagel, S; Vargas Trevino, A D R; Walsh, R; Wissing, C; Blobel, V; Centis Vignali, M; Draeger, A R; Erfle, J; Garutti, E; Goebel, K; Görner, M; Haller, J; Hoffmann, M; Höing, R S; Junkes, A; Kirschenmann, H; Klanner, R; Kogler, R; Lapsien, T; Lenz, T; Marchesini, I; Marconi, D; Nowatschin, D; Ott, J; Peiffer, T; Perieanu, A; Pietsch, N; Poehlsen, J; Poehlsen, T; Rathjens, D; Sander, C; Schettler, H; Schleper, P; Schlieckau, E; Schmidt, A; Seidel, M; Sola, V; Stadie, H; Steinbrück, G; Troendle, D; Usai, E; Vanelderen, L; Vanhoefer, A; Akbiyik, M; Barth, C; Baus, C; Berger, J; Böser, C; Butz, E; Chwalek, T; De Boer, W; Descroix, A; Dierlamm, A; Feindt, M; Frensch, F; Giffels, M; Gilbert, A; Hartmann, F; Hauth, T; Husemann, U; Katkov, I; Kornmayer, A; Lobelle Pardo, P; Mozer, M U; Müller, T; Müller, Th; Nürnberg, A; Quast, G; Rabbertz, K; Röcker, S; Simonis, H J; Stober, F M; Ulrich, R; Wagner-Kuhr, J; Wayand, S; Weiler, T; Wöhrmann, C; Wolf, R; Anagnostou, G; Daskalakis, G; Geralis, T; Giakoumopoulou, V A; Kyriakis, A; Loukas, D; Markou, A; Markou, C; Psallidas, A; Topsis-Giotis, I; Agapitos, A; Kesisoglou, S; Panagiotou, A; Saoulidou, N; Stiliaris, E; Tziaferi, E; Aslanoglou, X; Evangelou, I; Flouris, G; Foudas, C; Kokkas, P; Manthos, N; Papadopoulos, I; Strologas, J; Paradas, E; Bencze, G; Hajdu, C; Hidas, P; Horvath, D; Sikler, F; Veszpremi, V; Vesztergombi, G; Zsigmond, A J; Beni, N; Czellar, S; Karancsi, J; Molnar, J; Palinkas, J; Szillasi, Z; Makovec, A; Raics, P; Trocsanyi, Z L; Ujvari, B; Swain, S K; Beri, S B; Bhatnagar, V; Gupta, R; Bhawandeep, U; Kalsi, A K; Kaur, M; Kumar, R; Mittal, M; Nishu, N; Singh, J B; Kumar, Ashok; Kumar, Arun; Ahuja, S; Bhardwaj, A; Choudhary, B C; Kumar, A; Malhotra, S; Naimuddin, M; Ranjan, K; Sharma, V; Banerjee, S; Bhattacharya, S; Chatterjee, K; Dutta, S; Gomber, B; Jain, Sa; Jain, Sh; Khurana, R; Modak, A; Mukherjee, S; Roy, D; Sarkar, S; Sharan, M; Abdulsalam, A; Dutta, D; Kumar, V; Mohanty, A K; Pant, L M; Shukla, P; Topkar, A; Aziz, T; Banerjee, S; Bhowmik, S; Chatterjee, R M; 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Calvert, B; Eno, S C; Gomez, J A; Hadley, N J; Jabeen, S; Kellogg, R G; Kolberg, T; Lu, Y; Mignerey, A C; Pedro, K; Shin, Y H; Skuja, A; Tonjes, M B; Tonwar, S C; Apyan, A; Barbieri, R; Baty, A; Bierwagen, K; Brandt, S; Busza, W; Cali, I A; Di Matteo, L; Gomez Ceballos, G; Goncharov, M; Gulhan, D; Klute, M; Lai, Y S; Lee, Y-J; Levin, A; Luckey, P D; Paus, C; Ralph, D; Roland, C; Roland, G; Stephans, G S F; Sumorok, K; Velicanu, D; Veverka, J; Wyslouch, B; Yang, M; Yoon, A S; Zanetti, M; Zhukova, V; Dahmes, B; De Benedetti, A; Gude, A; Kao, S C; Klapoetke, K; Kubota, Y; Mans, J; Nourbakhsh, S; Rusack, R; Singovsky, A; Tambe, N; Turkewitz, J; Acosta, J G; Cremaldi, L M; Kroeger, R; Oliveros, S; Perera, L; Sanders, D A; Summers, D; Avdeeva, E; Bloom, K; Bose, S; Claes, D R; Dominguez, A; Gonzalez Suarez, R; Keller, J; Knowlton, D; Kravchenko, I; Lazo-Flores, J; Meier, F; Ratnikov, F; Snow, G R; Zvada, M; Dolen, J; Godshalk, A; Iashvili, I; Jain, S; Kharchilava, A; Kumar, A; Rappoccio, S; Alverson, G; Barberis, E; Baumgartel, D; Chasco, M; Massironi, A; Nash, D; Orimoto, T; Trocino, D; Wood, D; Zhang, J; Anastassov, A; Hahn, K A; Kubik, A; Lusito, L; Mucia, N; Odell, N; Pollack, B; Pozdnyakov, A; Schmitt, M; Stoynev, S; Sung, K; Trovato, M; Velasco, M; Won, S; Brinkerhoff, A; Chan, K M; Drozdetskiy, A; Hildreth, M; Jessop, C; Karmgard, D J; Kellams, N; Lannon, K; Lynch, S; Marinelli, N; Musienko, Y; Pearson, T; Planer, M; Ruchti, R; Valls, N; Smith, G; Wayne, M; Wolf, M; Woodard, A; Antonelli, L; Brinson, J; Bylsma, B; Durkin, L S; Flowers, S; Hart, A; Hill, C; Hughes, R; Kotov, K; Ling, T Y; Luo, W; Puigh, D; Rodenburg, M; Winer, B L; Wolfe, H; Wulsin, H W; Driga, O; Elmer, P; Hardenbrook, J; Hebda, P; Koay, S A; Lujan, P; Marlow, D; Medvedeva, T; Mooney, M; Olsen, J; Piroué, P; Quan, X; Saka, H; Stickland, D; Tully, C; Werner, J S; Zuranski, A; Brownson, E; Malik, S; Mendez, H; Ramirez Vargas, J E; Barnes, V E; Benedetti, D; Bortoletto, D; Gutay, L; Hu, Z; Jha, M K; Jones, M; Jung, K; Kress, M; Leonardo, N; Miller, D H; Neumeister, N; Primavera, F; Radburn-Smith, B C; Shi, X; Shipsey, I; Silvers, D; Svyatkovskiy, A; Wang, F; Xie, W; Xu, L; Zablocki, J; Parashar, N; Stupak, J; Adair, A; Akgun, B; Ecklund, K M; Geurts, F J M; Li, W; Michlin, B; Padley, B P; Redjimi, R; Roberts, J; Zabel, J; Betchart, B; Bodek, A; de Barbaro, P; Demina, R; Eshaq, Y; Ferbel, T; Galanti, M; Garcia-Bellido, A; Goldenzweig, P; Han, J; Harel, A; Hindrichs, O; Khukhunaishvili, A; Korjenevski, S; Petrillo, G; Verzetti, M; Vishnevskiy, D; Ciesielski, R; Demortier, L; Goulianos, K; Mesropian, C; Arora, S; Barker, A; Chou, J P; Contreras-Campana, C; Contreras-Campana, E; Duggan, D; Ferencek, D; Gershtein, Y; Gray, R; Halkiadakis, E; Hidas, D; Hughes, E; Kaplan, S; Kunnawalkam Elayavalli, R; Lath, A; Panwalkar, S; Park, M; Salur, S; Schnetzer, S; Sheffield, D; Somalwar, S; Stone, R; Thomas, S; Thomassen, P; Walker, M; Rose, K; Spanier, S; York, A; Bouhali, O; Castaneda Hernandez, A; Dalchenko, M; De Mattia, M; Dildick, S; Eusebi, R; Flanagan, W; Gilmore, J; Kamon, T; Khotilovich, V; Krutelyov, V; Montalvo, R; Osipenkov, I; Pakhotin, Y; Patel, R; Perloff, A; Roe, J; Rose, A; Safonov, A; Suarez, I; Tatarinov, A; Ulmer, K A; Akchurin, N; Cowden, C; Damgov, J; Dragoiu, C; Dudero, P R; Faulkner, J; Kovitanggoon, K; Kunori, S; Lee, S W; Libeiro, T; Volobouev, I; Appelt, E; Delannoy, A G; Greene, S; Gurrola, A; Johns, W; Maguire, C; Mao, Y; Melo, A; Sharma, M; Sheldon, P; Snook, B; Tuo, S; Velkovska, J; Arenton, M W; Boutle, S; Cox, B; Francis, B; Goodell, J; Hirosky, R; Ledovskoy, A; Li, H; Lin, C; Neu, C; Wolfe, E; Wood, J; Clarke, C; Harr, R; Karchin, P E; Kottachchi Kankanamge Don, C; Lamichhane, P; Sturdy, J; Belknap, D A; Carlsmith, D; Cepeda, M; Dasu, S; Dodd, L; Duric, S; Friis, E; Hall-Wilton, R; Herndon, M; Hervé, A; Klabbers, P; Lanaro, A; Lazaridis, C; Levine, A; Loveless, R; Mohapatra, A; Ojalvo, I; Perry, T; Pierro, G A; Polese, G; Ross, I; Sarangi, T; Savin, A; Smith, W H; Taylor, D; Vuosalo, C; Woods, N; Collaboration, Authorinst The Cms

A search for a standard model Higgs boson produced in association with a top-quark pair and decaying to bottom quarks is presented. Events with hadronic jets and one or two oppositely charged leptons are selected from a data sample corresponding to an integrated luminosity of 19.5[Formula: see text] collected by the CMS experiment at the LHC in [Formula: see text] collisions at a centre-of-mass energy of 8[Formula: see text]. In order to separate the signal from the larger [Formula: see text]  + jets background, this analysis uses a matrix element method that assigns a probability density value to each reconstructed event under signal or background hypotheses. The ratio between the two values is used in a maximum likelihood fit to extract the signal yield. The results are presented in terms of the measured signal strength modifier, [Formula: see text], relative to the standard model prediction for a Higgs boson mass of 125[Formula: see text]. The observed (expected) exclusion limit at a 95 % confidence level is [Formula: see text] (3.3), corresponding to a best fit value [Formula: see text].

TERMA Framework for Biomedical Signal Analysis: An Economic-Inspired Approach

PubMed Central

Elgendi, Mohamed

2016-01-01

Biomedical signals contain features that represent physiological events, and each of these events has peaks. The analysis of biomedical signals for monitoring or diagnosing diseases requires the detection of these peaks, making event detection a crucial step in biomedical signal processing. Many researchers have difficulty detecting these peaks to investigate, interpret and analyze their corresponding events. To date, there is no generic framework that captures these events in a robust, efficient and consistent manner. A new method referred to for the first time as two event-related moving averages (“TERMA”) involves event-related moving averages and detects events in biomedical signals. The TERMA framework is flexible and universal and consists of six independent LEGO building bricks to achieve high accuracy detection of biomedical events. Results recommend that the window sizes for the two moving averages (W1 and W2) have to follow the inequality (8×W1)≥W2≥(2×W1). Moreover, TERMA is a simple yet efficient event detector that is suitable for wearable devices, point-of-care devices, fitness trackers and smart watches, compared to more complex machine learning solutions. PMID:27827852

Effects of detector dead-time on quantitative analyses involving boron and multi-hit detection events in atom probe tomography.

PubMed

Meisenkothen, Frederick; Steel, Eric B; Prosa, Ty J; Henry, Karen T; Prakash Kolli, R

2015-12-01

In atom probe tomography (APT), some elements tend to field evaporate preferentially in multi-hit detection events. Boron (B) is one such element. It is thought that a large fraction of the B signal may be lost during data acquisition and is not reported in the mass spectrum or in the 3-D APT reconstruction. Understanding the relationship between the field evaporation behavior of B and the limitations for detecting multi-hit events can provide insight into the signal loss mechanism for B and may suggest ways to improve B detection accuracy. The present work reports data for nominally pure B and for B-implanted silicon (Si) (NIST-SRM2137) at dose levels two-orders of magnitude lower than previously studied by Da Costa, et al. in 2012. Boron concentration profiles collected from SRM2137 specimens qualitatively confirmed a signal loss mechanism is at work in laser pulsed atom probe measurements of B in Si. Ion correlation analysis was used to graphically demonstrate that the detector dead-time results in few same isotope, same charge-state (SISCS) ion pairs being properly recorded in the multi-hit data, explaining why B is consistently under-represented in quantitative analyses. Given the important role of detector dead-time as a signal loss mechanism, the results from three different methods of estimating the detector dead-time are presented. The findings of this study apply to all quantitative analyses that involve multi-hit data, but the dead-time will have the greatest effect on the elements that have a significant quantity of ions detected in multi-hit events. Published by Elsevier B.V.

Accuracy-Energy Configurable Sensor Processor and IoT Device for Long-Term Activity Monitoring in Rare-Event Sensing Applications

PubMed Central

2014-01-01

A specially designed sensor processor used as a main processor in IoT (internet-of-thing) device for the rare-event sensing applications is proposed. The IoT device including the proposed sensor processor performs the event-driven sensor data processing based on an accuracy-energy configurable event-quantization in architectural level. The received sensor signal is converted into a sequence of atomic events, which is extracted by the signal-to-atomic-event generator (AEG). Using an event signal processing unit (EPU) as an accelerator, the extracted atomic events are analyzed to build the final event. Instead of the sampled raw data transmission via internet, the proposed method delays the communication with a host system until a semantic pattern of the signal is identified as a final event. The proposed processor is implemented on a single chip, which is tightly coupled in bus connection level with a microcontroller using a 0.18 μm CMOS embedded-flash process. For experimental results, we evaluated the proposed sensor processor by using an IR- (infrared radio-) based signal reflection and sensor signal acquisition system. We successfully demonstrated that the expected power consumption is in the range of 20% to 50% compared to the result of the basement in case of allowing 10% accuracy error. PMID:25580458

Molecular basis of hypohidrotic ectodermal dysplasia: an update.

PubMed

Trzeciak, Wieslaw H; Koczorowski, Ryszard

2016-02-01

Recent advances in understanding the molecular events underlying hypohidrotic ectodermal dysplasia (HED) caused by mutations of the genes encoding proteins of the tumor necrosis factor α (TNFα)-related signaling pathway have been presented. These proteins are involved in signal transduction from ectoderm to mesenchyme during development of the fetus and are indispensable for the differentiation of ectoderm-derived structures such as eccrine sweat glands, teeth, hair, skin, and/or nails. Novel data were reviewed and discussed on the structure and functions of the components of TNFα-related signaling pathway, the consequences of mutations of the genes encoding these proteins, and the prospect for further investigations, which might elucidate the origin of HED.

Hydroacoustic monitoring of a salt cavity: an analysis of precursory events of the collapse

NASA Astrophysics Data System (ADS)

Lebert, F.; Bernardie, S.; Mainsant, G.

2011-09-01

One of the main features of "post mining" research relates to available methods for monitoring mine-degradation processes that could directly threaten surface infrastructures. In this respect, GISOS, a French scientific interest group, is investigating techniques for monitoring the eventual collapse of underground cavities. One of the methods under investigation was monitoring the stability of a salt cavity through recording microseismic-precursor signals that may indicate the onset of rock failure. The data were recorded in a salt mine in Lorraine (France) when monitoring the controlled collapse of 2 000 000 m3 of rocks surrounding a cavity at 130 m depth. The monitoring in the 30 Hz to 3 kHz frequency range highlights the occurrence of events with high energy during periods of macroscopic movement, once the layers had ruptured; they appear to be the consequence of the post-rupture rock movements related to the intense deformation of the cavity roof. Moreover the analysis shows the presence of some interesting precursory signals before the cavity collapsed. They occurred a few hours before the failure phases, when the rocks were being weakened and damaged. They originated from the damaging and breaking process, when micro-cracks appear and then coalesce. From these results we expect that deeper signal analysis and statistical analysis on the complete event time distribution (several millions of files) will allow us to finalize a complete typology of each signal families and their relations with the evolution steps of the cavity over the five years monitoring.

Modeling pedestrian crossing speed profiles considering speed change behavior for the safety assessment of signalized intersections.

PubMed

Iryo-Asano, Miho; Alhajyaseen, Wael K M

2017-11-01

Pedestrian safety is one of the most challenging issues in road networks. Understanding how pedestrians maneuver across an intersection is the key to applying countermeasures against traffic crashes. It is known that the behaviors of pedestrians at signalized crosswalks are significantly different from those in ordinary walking spaces, and they are highly influenced by signal indication, potential conflicts with vehicles, and intersection geometries. One of the most important characteristics of pedestrian behavior at crosswalks is the possible sudden speed change while crossing. Such sudden behavioral change may not be expected by conflicting vehicles, which may lead to hazardous situations. This study aims to quantitatively model the sudden speed changes of pedestrians as they cross signalized crosswalks under uncongested conditions. Pedestrian speed profiles are collected from empirical data and speed change events are extracted assuming that the speed profiles are stepwise functions. The occurrence of speed change events is described by a discrete choice model as a function of the necessary walking speed to complete crossing before the red interval ends, current speed, and the presence of turning vehicles in the conflict area. The amount of speed change before and after the event is modeled using regression analysis. A Monte Carlo simulation is applied for the entire speed profile of the pedestrians. The results show that the model can represent the pedestrian travel time distribution more accurately than the constant speed model. Copyright © 2017 Elsevier Ltd. All rights reserved.

Error-Rate Estimation Based on Multi-Signal Flow Graph Model and Accelerated Radiation Tests

PubMed Central

Wang, Yueke; Xing, Kefei; Deng, Wei; Zhang, Zelong

2016-01-01

A method of evaluating the single-event effect soft-error vulnerability of space instruments before launched has been an active research topic in recent years. In this paper, a multi-signal flow graph model is introduced to analyze the fault diagnosis and meantime to failure (MTTF) for space instruments. A model for the system functional error rate (SFER) is proposed. In addition, an experimental method and accelerated radiation testing system for a signal processing platform based on the field programmable gate array (FPGA) is presented. Based on experimental results of different ions (O, Si, Cl, Ti) under the HI-13 Tandem Accelerator, the SFER of the signal processing platform is approximately 10−3(error/particle/cm2), while the MTTF is approximately 110.7 h. PMID:27583533

Error-Rate Estimation Based on Multi-Signal Flow Graph Model and Accelerated Radiation Tests.

PubMed

He, Wei; Wang, Yueke; Xing, Kefei; Deng, Wei; Zhang, Zelong

2016-01-01

A method of evaluating the single-event effect soft-error vulnerability of space instruments before launched has been an active research topic in recent years. In this paper, a multi-signal flow graph model is introduced to analyze the fault diagnosis and meantime to failure (MTTF) for space instruments. A model for the system functional error rate (SFER) is proposed. In addition, an experimental method and accelerated radiation testing system for a signal processing platform based on the field programmable gate array (FPGA) is presented. Based on experimental results of different ions (O, Si, Cl, Ti) under the HI-13 Tandem Accelerator, the SFER of the signal processing platform is approximately 10-3(error/particle/cm2), while the MTTF is approximately 110.7 h.

Prediction suppression and surprise enhancement in monkey inferotemporal cortex.

PubMed

Ramachandran, Suchitra; Meyer, Travis; Olson, Carl R

2017-07-01

Exposing monkeys, over the course of days and weeks, to pairs of images presented in fixed sequence, so that each leading image becomes a predictor for the corresponding trailing image, affects neuronal visual responsiveness in area TE. At the end of the training period, neurons respond relatively weakly to a trailing image when it appears in a trained sequence and, thus, confirms prediction, whereas they respond relatively strongly to the same image when it appears in an untrained sequence and, thus, violates prediction. This effect could arise from prediction suppression (reduced firing in response to the occurrence of a probable event) or surprise enhancement (elevated firing in response to the omission of a probable event). To identify its cause, we compared firing under the prediction-confirming and prediction-violating conditions to firing under a prediction-neutral condition. The results provide strong evidence for prediction suppression and limited evidence for surprise enhancement. NEW & NOTEWORTHY In predictive coding models of the visual system, neurons carry signed prediction error signals. We show here that monkey inferotemporal neurons exhibit prediction-modulated firing, as posited by these models, but that the signal is unsigned. The response to a prediction-confirming image is suppressed, and the response to a prediction-violating image may be enhanced. These results are better explained by a model in which the visual system emphasizes unpredicted events than by a predictive coding model. Copyright © 2017 the American Physiological Society.

Prohibitin as an oxidative stress biomarker in the eye

PubMed Central

Lee, Hyunju; Arnouk, Hilal; Sripathi, Srinivas; Chen, Ping; Zhang, Ruonan; Hunt, Richard C.; Hrushesky, William J. M.; Chung, Hyewon; Lee, Sung Haeng; Jahng, Wan Jin

2016-01-01

Identification of biomarker proteins in the retina and the retinal pigment epithelium (RPE) under oxidative stress may imply new insights into signaling mechanisms of retinal degeneration at the molecular level. Proteomic data from an in vivo mice model in constant light and an in vitro oxidative stress model are compared to controls under normal conditions. Our proteomic study shows that prohibitin is involved in oxidative stress signaling in the retina and RPE. The identity of prohibitin in the retina and the RPE was studied using 2D electrophoresis, immunohistochemistry, western blot, and mass spectrometry analysis. Comparison of expression levels with apoptotic markers as well as translocation between mitochondria and the nucleus imply that the regulation of prohibitin is an early signaling event in the RPE and retina under oxidative stress. Immunohistochemical analysis of murine aged and diabetic eyes further suggests that the regulation of prohibitin in the RPE/retina is related to aging- and diabetes-induced oxidative stress. Our proteomic approach implies that prohibitin in the RPE and the retina could be a new biomarker protein of oxidative stress in aging and diabetes. PMID:20832420

Prohibitin as an oxidative stress biomarker in the eye.

PubMed

Lee, Hyunju; Arnouk, Hilal; Sripathi, Srinivas; Chen, Ping; Zhang, Ruonan; Bartoli, Manuela; Hunt, Richard C; Hrushesky, William J M; Chung, Hyewon; Lee, Sung Haeng; Jahng, Wan Jin

2010-12-01

Identification of biomarker proteins in the retina and retinal pigment epithelium (RPE) under oxidative stress may imply new insights into signaling mechanisms of retinal degeneration at the molecular level. Proteomic data from an in vivo mice model in constant light and an in vitro oxidative stress model are compared to controls under normal conditions. Our proteomic study shows that prohibitin is involved in oxidative stress signaling in the retina and RPE. The identity of prohibitin in the retina and RPE was studied using 2D electrophoresis, immunohistochemistry, western blot, and mass spectrometry analysis. Comparison of expression levels with apoptotic markers as well as translocation between mitochondria and the nucleus imply that the regulation of prohibitin is an early signaling event in the RPE and retina under oxidative stress. Immunohistochemical analysis of murine aged and diabetic eyes further suggests that the regulation of prohibitin in the RPE/retina is related to aging- and diabetes-induced oxidative stress. Our proteomic approach implies that prohibitin in the RPE and the retina could be a new biomarker protein of oxidative stress in aging and diabetes. Copyright © 2010 Elsevier B.V. All rights reserved.

DETECT: A MATLAB Toolbox for Event Detection and Identification in Time Series, with Applications to Artifact Detection in EEG Signals

DTIC Science & Technology

2013-04-24

DETECT: A MATLAB Toolbox for Event Detection and Identification in Time Series, with Applications to Artifact Detection in EEG Signals Vernon...datasets in the context of events, which are intervals of time where the properties of the signal change relative to a baseline signal . We have developed...As an illustration, we discuss application of the DETECT toolbox for detecting signal artifacts found in continuous multi-channel EEG recordings and

Anisotropy of demineralized bone matrix under compressive load.

PubMed

Trębacz, Hanna; Zdunek, Artur

2011-01-01

Two groups of cubic specimens from diaphysis of bovine femur, intact and completely demineralized, were axially compressed. One half of the samples from each group were loaded along the axis of the femur (L) and the other - perpendicularly (T). Intact samples were characterized in terms of elastic modulus; for demineralized samples secant modulus of elasticity was calculated. During compression an acoustic emission (AE) signal was recorded and AE events and energy were analyzed. Samples of intact bone did not reveal any anisotropy under compression at the stress of 80 MPa. However, AE signal indicated an initiation of failure in samples loaded in T direction. Demineralized samples were anisotropic under compression. Both secant modulus of elasticity and AE parameters were significantly higher in T direction than in L direction, which is attributed to shifting and separation of lamellae of collagen fibrils and lamellae in bone matrix.

Evolution and Design Governing Signal Precision and Amplification in a Bacterial Chemosensory Pathway

PubMed Central

Espinosa, Leon; Baronian, Grégory; Molle, Virginie; Mauriello, Emilia M. F.; Brochier-Armanet, Céline; Mignot, Tâm

2015-01-01

Understanding the principles underlying the plasticity of signal transduction networks is fundamental to decipher the functioning of living cells. In Myxococcus xanthus, a particular chemosensory system (Frz) coordinates the activity of two separate motility systems (the A- and S-motility systems), promoting multicellular development. This unusual structure asks how signal is transduced in a branched signal transduction pathway. Using combined evolution-guided and single cell approaches, we successfully uncoupled the regulations and showed that the A-motility regulation system branched-off an existing signaling system that initially only controlled S-motility. Pathway branching emerged in part following a gene duplication event and changes in the circuit structure increasing the signaling efficiency. In the evolved pathway, the Frz histidine kinase generates a steep biphasic response to increasing external stimulations, which is essential for signal partitioning to the motility systems. We further show that this behavior results from the action of two accessory response regulator proteins that act independently to filter and amplify signals from the upstream kinase. Thus, signal amplification loops may underlie the emergence of new connectivity in signal transduction pathways. PMID:26291327

Model-Based Adaptive Event-Triggered Control of Strict-Feedback Nonlinear Systems.

PubMed

Li, Yuan-Xin; Yang, Guang-Hong

2018-04-01

This paper is concerned with the adaptive event-triggered control problem of nonlinear continuous-time systems in strict-feedback form. By using the event-sampled neural network (NN) to approximate the unknown nonlinear function, an adaptive model and an associated event-triggered controller are designed by exploiting the backstepping method. In the proposed method, the feedback signals and the NN weights are aperiodically updated only when the event-triggered condition is violated. A positive lower bound on the minimum intersample time is guaranteed to avoid accumulation point. The closed-loop stability of the resulting nonlinear impulsive dynamical system is rigorously proved via Lyapunov analysis under an adaptive event sampling condition. In comparing with the traditional adaptive backstepping design with a fixed sample period, the event-triggered method samples the state and updates the NN weights only when it is necessary. Therefore, the number of transmissions can be significantly reduced. Finally, two simulation examples are presented to show the effectiveness of the proposed control method.

The cell envelope stress response of Bacillus subtilis: from static signaling devices to dynamic regulatory network.

PubMed

Radeck, Jara; Fritz, Georg; Mascher, Thorsten

2017-02-01

The cell envelope stress response (CESR) encompasses all regulatory events that enable a cell to protect the integrity of its envelope, an essential structure of any bacterial cell. The underlying signaling network is particularly well understood in the Gram-positive model organism Bacillus subtilis. It consists of a number of two-component systems (2CS) and extracytoplasmic function σ factors that together regulate the production of both specific resistance determinants and general mechanisms to protect the envelope against antimicrobial peptides targeting the biogenesis of the cell wall. Here, we summarize the current picture of the B. subtilis CESR network, from the initial identification of the corresponding signaling devices to unraveling their interdependence and the underlying regulatory hierarchy within the network. In the course of detailed mechanistic studies, a number of novel signaling features could be described for the 2CSs involved in mediating CESR. This includes a novel class of so-called intramembrane-sensing histidine kinases (IM-HKs), which-instead of acting as stress sensors themselves-are activated via interprotein signal transfer. Some of these IM-HKs are involved in sensing the flux of antibiotic resistance transporters, a unique mechanism of responding to extracellular antibiotic challenge.

AKAP-Lbc enhances cyclic AMP control of the ERK1/2 cascade.

PubMed

Smith, F Donelson; Langeberg, Lorene K; Cellurale, Cristina; Pawson, Tony; Morrison, Deborah K; Davis, Roger J; Scott, John D

2010-12-01

Mitogen-activated protein kinase (MAPK) cascades propagate a variety of cellular activities. Processive relay of signals through RAF-MEK-ERK modulates cell growth and proliferation. Signalling through this ERK cascade is frequently amplified in cancers, and drugs such as sorafenib (which is prescribed to treat renal and hepatic carcinomas) and PLX4720 (which targets melanomas) inhibit RAF kinases. Natural factors that influence ERK1/2 signalling include the second messenger cyclic AMP. However, the mechanisms underlying this cascade have been difficult to elucidate. We demonstrate that the A-kinase-anchoring protein AKAP-Lbc and the scaffolding protein kinase suppressor of Ras (KSR-1) form the core of a signalling network that efficiently relay signals from RAF, through MEK, and on to ERK1/2. AKAP-Lbc functions as an enhancer of ERK signalling by securing RAF in the vicinity of MEK1 and synchronizing protein kinase A (PKA)-mediated phosphorylation of Ser 838 on KSR-1. This offers mechanistic insight into cAMP-responsive control of ERK signalling events.

Aberrant Cortical Activity in Multiple GCaMP6-Expressing Transgenic Mouse Lines

PubMed Central

Buetfering, Christina; Groblewski, Peter A.; Manavi, Sahar; Miles, Jesse; White, Casey; Griffin, Fiona; Roll, Kate; Cross, Sissy; Nguyen, Thuyanh V.; Larsen, Rachael; Daigle, Tanya; Thompson, Carol L.; Olsen, Shawn; Hausser, Michael

2017-01-01

Abstract Transgenic mouse lines are invaluable tools for neuroscience but, as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, of either sex, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, although rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study. PMID:28932809

Jasmonates: Multifunctional Roles in Stress Tolerance

PubMed Central

Ahmad, Parvaiz; Rasool, Saiema; Gul, Alvina; Sheikh, Subzar A.; Akram, Nudrat A.; Ashraf, Muhammad; Kazi, A. M.; Gucel, Salih

2016-01-01

Jasmonates (JAs) [Jasmonic acid (JA) and methyl jasmonates (MeJAs)] are known to take part in various physiological processes. Exogenous application of JAs so far tested on different plants under abiotic stresses particularly salinity, drought, and temperature (low/high) conditions have proved effective in improving plant stress tolerance. However, its extent of effectiveness entirely depends on the type of plant species tested or its concentration. The effects of introgression or silencing of different JA- and Me-JA-related genes have been summarized in this review, which have shown a substantial role in improving crop yield and quality in different plants under stress or non-stress conditions. Regulation of JAs synthesis is impaired in stressed as well as unstressed plant cells/tissues, which is believed to be associated with a variety of metabolic events including signal transduction. Although, mitogen activated protein kinases (MAPKs) are important components of JA signaling and biosynthesis pathways, nitric oxide, ROS, calcium, ABA, ethylene, and salicylic acid are also important mediators of plant growth and development during JA signal transduction and synthesis. The exploration of other signaling molecules can be beneficial to examine the details of underlying molecular mechanisms of JA signal transduction. Much work is to be done in near future to find the proper answers of the questions like action of JA related metabolites, and identification of universal JA receptors etc. Complete signaling pathways involving MAPKs, CDPK, TGA, SIPK, WIPK, and WRKY transcription factors are yet to be investigated to understand the complete mechanism of action of JAs. PMID:27379115

Commonality of drug-associated adverse events detected by 4 commonly used data mining algorithms.

PubMed

Sakaeda, Toshiyuki; Kadoyama, Kaori; Minami, Keiko; Okuno, Yasushi

2014-01-01

Data mining algorithms have been developed for the quantitative detection of drug-associated adverse events (signals) from a large database on spontaneously reported adverse events. In the present study, the commonality of signals detected by 4 commonly used data mining algorithms was examined. A total of 2,231,029 reports were retrieved from the public release of the US Food and Drug Administration Adverse Event Reporting System database between 2004 and 2009. The deletion of duplicated submissions and revision of arbitrary drug names resulted in a reduction in the number of reports to 1,644,220. Associations with adverse events were analyzed for 16 unrelated drugs, using the proportional reporting ratio (PRR), reporting odds ratio (ROR), information component (IC), and empirical Bayes geometric mean (EBGM). All EBGM-based signals were included in the PRR-based signals as well as IC- or ROR-based ones, and PRR- and IC-based signals were included in ROR-based ones. The PRR scores of PRR-based signals were significantly larger for 15 of 16 drugs when adverse events were also detected as signals by the EBGM method, as were the IC scores of IC-based signals for all drugs; however, no such effect was observed in the ROR scores of ROR-based signals. The EBGM method was the most conservative among the 4 methods examined, which suggested its better suitability for pharmacoepidemiological studies. Further examinations should be performed on the reproducibility of clinical observations, especially for EBGM-based signals.

The neural correlates of trait resilience when anticipating and recovering from threat

PubMed Central

Waugh, Christian E.; Wager, Tor D.; Fredrickson, Barbara L.; Noll, Doug C.; Taylor, Stephan F.

2008-01-01

A facet of emotional resilience critical for adapting to adversity is flexible use of emotional resources. We hypothesized that in threatening situations, this emotional flexibility enables resilient people to use emotional resources during appropriately emotional events, and conserve emotional resources during innocuous events. We tested this hypothesis using functional magnetic resonance imaging in a repeated recovery from threat task with low- and high-trait resilient individuals (LowR and HighR, respectively, as measured by ER89). In an event-related design, 13 HighR and 13 LowR participants viewed ‘threat’ cues, which signaled either an aversive or neutral picture with equal probabilities, or ‘nonthreat’ cues, which signaled a neutral picture. Results show that when under threat, LowR individuals exhibited prolonged activation in the anterior insula to both the aversive and neutral pictures, whereas HighR individuals exhibited insula activation only to the aversive pictures. These data provide neural evidence that in threatening situations, resilient people flexibly and appropriately adjust the level of emotional resources needed to meet the demands of the situation. PMID:19015078

Left prefrontal cortex control of novel occurrences during recollection: a psychopharmacological study using scopolamine and event-related fMRI.

PubMed

Bozzali, M; MacPherson, S E; Dolan, R J; Shallice, T

2006-10-15

Recollection and familiarity represent two processes involved in episodic memory retrieval. We investigated how scopolamine (an antagonist of acetylcholine muscarinic receptors) influenced brain activity during memory retrieval, using a paradigm that separated recollection and familiarity. Eighteen healthy volunteers were recruited in a randomized, placebo-controlled, double-blind design using event-related fMRI. Participants were required to perform a verbal recognition memory task within the scanner, either under placebo or scopolamine conditions. Depending on the subcondition, participants were required to make a simple recognition decision (old/new items) or base their decision on more specific information related to prior experience (target/non-target/new items). We show a drug modulation in left prefrontal and perirhinal cortex during recollection. Such an effect was specifically driven by novelty and showed an inverse correlation with accuracy performance. Additionally, we show a direct correlation between drug-related signal change in left prefrontal and perirhinal cortices. We discuss the findings in terms of acetylcholine mediation of the familiarity/novelty signal through perirhinal cortex and the control of the relative signal strength through prefrontal cortex.

E4orf1 induction in adipose tissue promotes insulin-independent signaling in the adipocyte

PubMed Central

Kusminski, Christine M.; Gallardo-Montejano, Violeta I.; Wang, Zhao V.; Hegde, Vijay; Bickel, Perry E.; Dhurandhar, Nikhil V.; Scherer, Philipp E.

2015-01-01

Background/Purpose Type 2 diabetes remains a worldwide epidemic with major pathophysiological changes as a result of chronic insulin resistance. Insulin regulates numerous biochemical pathways related to carbohydrate and lipid metabolism. Methods We have generated a novel mouse model that allows us to constitutively activate, in an inducible fashion, the distal branch of the insulin signaling transduction pathway specifically in adipocytes. Results Using the adenoviral 36 E4orf1 protein, we chronically stimulate locally the Ras-ERK-MAPK signaling pathway. At the whole body level, this leads to reduced body-weight gain under a high fat diet challenge. Despite overlapping glucose tolerance curves, there is a reduced requirement for insulin action under these conditions. The mice further exhibit reduced circulating adiponectin levels that ultimately lead to impaired lipid clearance, and inflamed and fibrotic white adipose tissues. Nevertheless, they are protected from diet-induced hepatic steatosis. As we observe constitutively elevated p-Akt levels in the adipocytes, even under conditions of low insulin levels, this pinpoints enhanced Ras-ERK-MAPK signaling in transgenic adipocytes as a potential alternative route to bypass proximal insulin signaling events. Conclusion We conclude that E4orf1 expression in the adipocyte leads to enhanced baseline activation of the distal insulin signaling node, yet impaired insulin receptor stimulation in the presence of insulin, with important implications for the regulation of adiponectin secretion. The resulting systemic phenotype is complex, yet highlights the powerful nature of manipulating selective branches of the insulin signaling network within the adipocyte. PMID:26500839

Sensory Transduction and Electrical Signaling in Guard Cells

PubMed Central

Serrano, Elba E.; Zeiger, Eduardo

1989-01-01

Guard cells are a valuable model system for the study of photoreception, ion transport, and osmoregulation in plant cells. Changes in stomatal apertures occur when sensing mechanisms within the guard cells transduce environmental stimull into the ion fluxes and biosynthesis of organic solutes that regulate turgor. The electrical events mediating sensory transduction in guard cells can be characterized with a variety of electrophysiological recording techniques. Recent experiments applying the patch clamp method to guard cell protoplasts have demonstrated activation of electrogenic pumps by blue and red light as well as the presence of potassium channels in guard cell plasmalemma. Light activation of electrogenic proton pumping and the ensuing gating of voltage-dependent ion channels appear to be components of sensory transduction of the stomatal response to light. Mechanisms underlying stomatal control by environmental signals can be understood by studying electrical events associated with ion transport. PMID:16667138

Detection of Cardiopulmonary Activity and Related Abnormal Events Using Microsoft Kinect Sensor.

PubMed

Al-Naji, Ali; Chahl, Javaan

2018-03-20

Monitoring of cardiopulmonary activity is a challenge when attempted under adverse conditions, including different sleeping postures, environmental settings, and an unclear region of interest (ROI). This study proposes an efficient remote imaging system based on a Microsoft Kinect v2 sensor for the observation of cardiopulmonary-signal-and-detection-related abnormal cardiopulmonary events (e.g., tachycardia, bradycardia, tachypnea, bradypnea, and central apnoea) in many possible sleeping postures within varying environmental settings including in total darkness and whether the subject is covered by a blanket or not. The proposed system extracts the signal from the abdominal-thoracic region where cardiopulmonary activity is most pronounced, using a real-time image sequence captured by Kinect v2 sensor. The proposed system shows promising results in any sleep posture, regardless of illumination conditions and unclear ROI even in the presence of a blanket, whilst being reliable, safe, and cost-effective.

Detection of Cardiopulmonary Activity and Related Abnormal Events Using Microsoft Kinect Sensor

PubMed Central

Chahl, Javaan

2018-01-01

Monitoring of cardiopulmonary activity is a challenge when attempted under adverse conditions, including different sleeping postures, environmental settings, and an unclear region of interest (ROI). This study proposes an efficient remote imaging system based on a Microsoft Kinect v2 sensor for the observation of cardiopulmonary-signal-and-detection-related abnormal cardiopulmonary events (e.g., tachycardia, bradycardia, tachypnea, bradypnea, and central apnoea) in many possible sleeping postures within varying environmental settings including in total darkness and whether the subject is covered by a blanket or not. The proposed system extracts the signal from the abdominal-thoracic region where cardiopulmonary activity is most pronounced, using a real-time image sequence captured by Kinect v2 sensor. The proposed system shows promising results in any sleep posture, regardless of illumination conditions and unclear ROI even in the presence of a blanket, whilst being reliable, safe, and cost-effective. PMID:29558414

Automatic Classification of volcano-seismic events based on Deep Neural Networks.

NASA Astrophysics Data System (ADS)

Titos Luzón, M.; Bueno Rodriguez, A.; Garcia Martinez, L.; Benitez, C.; Ibáñez, J. M.

2017-12-01

Seismic monitoring of active volcanoes is a popular remote sensing technique to detect seismic activity, often associated to energy exchanges between the volcano and the environment. As a result, seismographs register a wide range of volcano-seismic signals that reflect the nature and underlying physics of volcanic processes. Machine learning and signal processing techniques provide an appropriate framework to analyze such data. In this research, we propose a new classification framework for seismic events based on deep neural networks. Deep neural networks are composed by multiple processing layers, and can discover intrinsic patterns from the data itself. Internal parameters can be initialized using a greedy unsupervised pre-training stage, leading to an efficient training of fully connected architectures. We aim to determine the robustness of these architectures as classifiers of seven different types of seismic events recorded at "Volcán de Fuego" (Colima, Mexico). Two deep neural networks with different pre-training strategies are studied: stacked denoising autoencoder and deep belief networks. Results are compared to existing machine learning algorithms (SVM, Random Forest, Multilayer Perceptron). We used 5 LPC coefficients over three non-overlapping segments as training features in order to characterize temporal evolution, avoid redundancy and encode the signal, regardless of its duration. Experimental results show that deep architectures can classify seismic events with higher accuracy than classical algorithms, attaining up to 92% recognition accuracy. Pre-training initialization helps these models to detect events that occur simultaneously in time (such explosions and rockfalls), increase robustness against noisy inputs, and provide better generalization. These results demonstrate deep neural networks are robust classifiers, and can be deployed in real-environments to monitor the seismicity of restless volcanoes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sajadian, Sedighe; Hundertmark, Markus, E-mail: s.sajadian@cc.iut.ac.ir

A close-in giant planetary (CGP) system has a net polarization signal whose value varies depending on the orbital phase of the planet. This polarization signal is either caused by the stellar occultation or by reflected starlight from the surface of the orbiting planet. When the CGP system is located in the Galactic bulge, its polarization signal becomes too weak to be measured directly. One method for detecting and characterizing these weak polarization signatures due to distant CGP systems is gravitational microlensing. In this work, we focus on potential polarimetric observations of highly magnified microlensing events of CGP systems. When themore » lens is passing directly in front of the source star with its planetary companion, the polarimetric signature caused by the transiting planet is magnified. As a result, some distinct features in the polarimetry and light curves are produced. In the same way, microlensing amplifies the reflection-induced polarization signal. While the planet-induced perturbations are magnified whenever these polarimetric or photometric deviations vanish for a moment, the corresponding magnification factor of the polarization component(s) is related to the planet itself. Finding these exact times in the planet-induced perturbations helps us to characterize the planet. In order to evaluate the observability of such systems through polarimetric or photometric observations of high-magnification microlensing events, we simulate these events by considering confirmed CGP systems as their source stars and conclude that the efficiency for detecting the planet-induced signal with the state-of-the-art polarimetric instrument (FORS2/VLT) is less than 0.1%. Consequently, these planet-induced polarimetry perturbations can likely be detected under favorable conditions by the high-resolution and short-cadence polarimeters of the next generation.« less

Polarimetry Microlensing of Close-in Planetary Systems

NASA Astrophysics Data System (ADS)

Sajadian, Sedighe; Hundertmark, Markus

2017-04-01

A close-in giant planetary (CGP) system has a net polarization signal whose value varies depending on the orbital phase of the planet. This polarization signal is either caused by the stellar occultation or by reflected starlight from the surface of the orbiting planet. When the CGP system is located in the Galactic bulge, its polarization signal becomes too weak to be measured directly. One method for detecting and characterizing these weak polarization signatures due to distant CGP systems is gravitational microlensing. In this work, we focus on potential polarimetric observations of highly magnified microlensing events of CGP systems. When the lens is passing directly in front of the source star with its planetary companion, the polarimetric signature caused by the transiting planet is magnified. As a result, some distinct features in the polarimetry and light curves are produced. In the same way, microlensing amplifies the reflection-induced polarization signal. While the planet-induced perturbations are magnified whenever these polarimetric or photometric deviations vanish for a moment, the corresponding magnification factor of the polarization component(s) is related to the planet itself. Finding these exact times in the planet-induced perturbations helps us to characterize the planet. In order to evaluate the observability of such systems through polarimetric or photometric observations of high-magnification microlensing events, we simulate these events by considering confirmed CGP systems as their source stars and conclude that the efficiency for detecting the planet-induced signal with the state-of-the-art polarimetric instrument (FORS2/VLT) is less than 0.1%. Consequently, these planet-induced polarimetry perturbations can likely be detected under favorable conditions by the high-resolution and short-cadence polarimeters of the next generation.

Temporal and spectral characteristics of seismicity observed at Popocatepetl volcano, central Mexico

USGS Publications Warehouse

Arciniega-Ceballos, A.; Valdes-Gonzalez, C.; Dawson, P.

2000-01-01

Popocatepetl volcano entered an eruptive phase from December 21, 1994 to March 30, 1995, which was characterized by ash and fumarolic emissions. During this eruptive episode, the observed seismicity consisted of volcano-tectonic (VT) events, long-period (LP) events and sustained tremor. Before the initial eruption on December 21, VT seismicity exhibited no increase in number until a swarm of VT earthquakes was observed at 01:31 hours local time. Visual observations of the eruption occurred at dawn the next morning. LP activity increased from an average of 7 events a day in October 1994 to 22 events per day in December 1994. At the onset of the eruption, LP activity peaked at 49 events per day. LP activity declined until mid-January 1995 when no events were observed. Tremor was first observed about one day after the initial eruption and averaged 10 h per episode. By late February 1995, tremor episodes became more intermittent, lasting less than 5 min, and the number of LP events returned to pre-eruption levels (7 events per day). Using a spectral ratio technique, low-frequency oceanic microseismic noise with a predominant peak around 7 s was removed from the broadband seismic signal of tremor and LP events. Stacks of corrected tremor episodes and LP events show that both tremor and LP events contain similar frequency features with major peaks around 1.4 Hz. Frequency analyses of LP events and tremor suggest a shallow extended source with similar radiation pattern characteristics. The distribution of VT events (between 2.5 and 10 km) also points to a shallow source of the tremor and LP events located in the first 2500 m beneath the crater. Under the assumption that the frequency characteristics of the signals are representative of an oscillator we used a fluid-filled-crack model to infer the length of the resonator.

Finding the signal in the noise: Could social media be utilized for early hospital notification of multiple casualty events?

PubMed Central

Moore, Sara; Wakam, Glenn; Hubbard, Alan E.; Cohen, Mitchell J.

2017-01-01

Introduction Delayed notification and lack of early information hinder timely hospital based activations in large scale multiple casualty events. We hypothesized that Twitter real-time data would produce a unique and reproducible signal within minutes of multiple casualty events and we investigated the timing of the signal compared with other hospital disaster notification mechanisms. Methods Using disaster specific search terms, all relevant tweets from the event to 7 days post-event were analyzed for 5 recent US based multiple casualty events (Boston Bombing [BB], SF Plane Crash [SF], Napa Earthquake [NE], Sandy Hook [SH], and Marysville Shooting [MV]). Quantitative and qualitative analysis of tweet utilization were compared across events. Results Over 3.8 million tweets were analyzed (SH 1.8 m, BB 1.1m, SF 430k, MV 250k, NE 205k). Peak tweets per min ranged from 209–3326. The mean followers per tweeter ranged from 3382–9992 across events. Retweets were tweeted a mean of 82–564 times per event. Tweets occurred very rapidly for all events (<2 mins) and represented 1% of the total event specific tweets in a median of 13 minutes of the first 911 calls. A 200 tweets/min threshold was reached fastest with NE (2 min), BB (7 min), and SF (18 mins). If this threshold was utilized as a signaling mechanism to place local hospitals on standby for possible large scale events, in all case studies, this signal would have preceded patient arrival. Importantly, this threshold for signaling would also have preceded traditional disaster notification mechanisms in SF, NE, and simultaneous with BB and MV. Conclusions Social media data has demonstrated that this mechanism is a powerful, predictable, and potentially important resource for optimizing disaster response. Further investigated is warranted to assess the utility of prospective signally thresholds for hospital based activation. PMID:28982201

Calcium specificity signaling mechanisms in abscisic acid signal transduction in Arabidopsis guard cells

PubMed Central

Brandt, Benjamin; Munemasa, Shintaro; Wang, Cun; Nguyen, Desiree; Yong, Taiming; Yang, Paul G; Poretsky, Elly; Belknap, Thomas F; Waadt, Rainer; Alemán, Fernando; Schroeder, Julian I

2015-01-01

A central question is how specificity in cellular responses to the eukaryotic second messenger Ca2+ is achieved. Plant guard cells, that form stomatal pores for gas exchange, provide a powerful system for in depth investigation of Ca2+-signaling specificity in plants. In intact guard cells, abscisic acid (ABA) enhances (primes) the Ca2+-sensitivity of downstream signaling events that result in activation of S-type anion channels during stomatal closure, providing a specificity mechanism in Ca2+-signaling. However, the underlying genetic and biochemical mechanisms remain unknown. Here we show impairment of ABA signal transduction in stomata of calcium-dependent protein kinase quadruple mutant plants. Interestingly, protein phosphatase 2Cs prevent non-specific Ca2+-signaling. Moreover, we demonstrate an unexpected interdependence of the Ca2+-dependent and Ca2+-independent ABA-signaling branches and the in planta requirement of simultaneous phosphorylation at two key phosphorylation sites in SLAC1. We identify novel mechanisms ensuring specificity and robustness within stomatal Ca2+-signaling on a cellular, genetic, and biochemical level. DOI: http://dx.doi.org/10.7554/eLife.03599.001 PMID:26192964

Correction: Calcium specificity signaling mechanisms in abscisic acid signal transduction in Arabidopsis guard cells

DOE PAGES

Brandt, Benjamin; Munemasa, Shintaro; Wang, Cun; ...

2015-07-20

One central question is how specificity in cellular responses to the eukaryotic second messenger Ca 2+ is achieved. Plant guard cells, that form stomatal pores for gas exchange, provide a powerful system for in depth investigation of Ca 2+-signaling specificity in plants. In intact guard cells, abscisic acid (ABA) enhances (primes) the Ca 2+-sensitivity of downstream signaling events that result in activation of S-type anion channels during stomatal closure, providing a specificity mechanism in Ca 2+-signaling. However, the underlying genetic and biochemical mechanisms remain unknown. Here we show impairment of ABA signal transduction in stomata of calcium-dependent protein kinase quadruplemore » mutant plants. Interestingly, protein phosphatase 2Cs prevent non-specific Ca 2+-signaling. Moreover, we demonstrate an unexpected interdependence of the Ca 2+-dependent and Ca 2+-independent ABA-signaling branches and the in planta requirement of simultaneous phosphorylation at two key phosphorylation sites in SLAC1. We identify novel mechanisms ensuring specificity and robustness within stomatal Ca 2+-signaling on a cellular, genetic, and biochemical level.« less

Correction: Calcium specificity signaling mechanisms in abscisic acid signal transduction in Arabidopsis guard cells

DOE PAGES

Brandt, Benjamin; Munemasa, Shintaro; Wang, Cun; ...

2015-07-29

A central question is how specificity in cellular responses to the eukaryotic second messenger Ca 2+ is achieved. Plant guard cells, that form stomatal pores for gas exchange, provide a powerful system for in depth investigation of Ca 2+-signaling specificity in plants. In intact guard cells, abscisic acid (ABA) enhances (primes) the Ca 2+-sensitivity of downstream signaling events that result in activation of S-type anion channels during stomatal closure, providing a specificity mechanism in Ca 2+-signaling. However, the underlying genetic and biochemical mechanisms remain unknown. Here we show impairment of ABA signal transduction in stomata of calcium-dependent protein kinase quadruplemore » mutant plants. Interestingly, protein phosphatase 2Cs prevent non-specific Ca 2+-signaling. Moreover, we demonstrate an unexpected interdependence of the Ca 2+-dependent and Ca 2+-independent ABA-signaling branches and the in planta requirement of simultaneous phosphorylation at two key phosphorylation sites in SLAC1. We identify novel mechanisms ensuring specificity and robustness within stomatal Ca 2+-signaling on a cellular, genetic, and biochemical level.« less

Shared performance monitor in a multiprocessor system

DOEpatents

Chiu, George; Gara, Alan G.; Salapura, Valentina

2012-07-24

A performance monitoring unit (PMU) and method for monitoring performance of events occurring in a multiprocessor system. The multiprocessor system comprises a plurality of processor devices units, each processor device for generating signals representing occurrences of events in the processor device, and, a single shared counter resource for performance monitoring. The performance monitor unit is shared by all processor cores in the multiprocessor system. The PMU comprises: a plurality of performance counters each for counting signals representing occurrences of events from one or more the plurality of processor units in the multiprocessor system; and, a plurality of input devices for receiving the event signals from one or more processor devices of the plurality of processor units, the plurality of input devices programmable to select event signals for receipt by one or more of the plurality of performance counters for counting, wherein the PMU is shared between multiple processing units, or within a group of processors in the multiprocessing system. The PMU is further programmed to monitor event signals issued from non-processor devices.

Global Profiling and Molecular Characterization of Alternative Splicing Events Misregulated in Lung Cancer ▿ †

PubMed Central

Misquitta-Ali, Christine M.; Cheng, Edith; O'Hanlon, Dave; Liu, Ni; McGlade, C. Jane; Tsao, Ming Sound; Blencowe, Benjamin J.

2011-01-01

Alternative splicing (AS) is a widespread mechanism underlying the generation of proteomic and regulatory complexity. However, which of the myriad of human AS events play important roles in disease is largely unknown. To identify frequently occurring AS events in lung cancer, we used AS microarray profiling and reverse transcription-PCR (RT-PCR) assays to survey patient-matched normal and adenocarcinoma tumor tissues from the lungs of 29 individuals diagnosed with non-small cell lung cancer (NSCLC). Of 5,183 profiled alternative exons, four displayed tumor-associated changes in the majority of the patients. These events affected transcripts from the VEGFA, MACF1, APP, and NUMB genes. Similar AS changes were detected in NUMB and APP transcripts in primary breast and colon tumors. Tumor-associated increases in NUMB exon 9 inclusion correlated with reduced levels of NUMB protein expression and activation of the Notch signaling pathway, an event that has been linked to tumorigenesis. Moreover, short hairpin RNA (shRNA) knockdown of NUMB followed by isoform-specific rescue revealed that expression of the exon 9-skipped (nontumor) isoform represses Notch target gene activation whereas expression of the exon 9-included (tumor) isoform lacks this activity and is capable of promoting cell proliferation. The results thus reveal widespread AS changes in NSCLC that impact cell signaling in a manner that likely contributes to tumorigenesis. PMID:21041478

Global profiling and molecular characterization of alternative splicing events misregulated in lung cancer.

PubMed

Misquitta-Ali, Christine M; Cheng, Edith; O'Hanlon, Dave; Liu, Ni; McGlade, C Jane; Tsao, Ming Sound; Blencowe, Benjamin J

2011-01-01

Alternative splicing (AS) is a widespread mechanism underlying the generation of proteomic and regulatory complexity. However, which of the myriad of human AS events play important roles in disease is largely unknown. To identify frequently occurring AS events in lung cancer, we used AS microarray profiling and reverse transcription-PCR (RT-PCR) assays to survey patient-matched normal and adenocarcinoma tumor tissues from the lungs of 29 individuals diagnosed with non-small cell lung cancer (NSCLC). Of 5,183 profiled alternative exons, four displayed tumor-associated changes in the majority of the patients. These events affected transcripts from the VEGFA, MACF1, APP, and NUMB genes. Similar AS changes were detected in NUMB and APP transcripts in primary breast and colon tumors. Tumor-associated increases in NUMB exon 9 inclusion correlated with reduced levels of NUMB protein expression and activation of the Notch signaling pathway, an event that has been linked to tumorigenesis. Moreover, short hairpin RNA (shRNA) knockdown of NUMB followed by isoform-specific rescue revealed that expression of the exon 9-skipped (nontumor) isoform represses Notch target gene activation whereas expression of the exon 9-included (tumor) isoform lacks this activity and is capable of promoting cell proliferation. The results thus reveal widespread AS changes in NSCLC that impact cell signaling in a manner that likely contributes to tumorigenesis.

Fine characterization rock thermal damage by acoustic emission technique

NASA Astrophysics Data System (ADS)

Kong, Biao; Li, Zenghua; Wang, Enyuan

2018-02-01

This paper examines the differences in the thermal mechanical properties and acoustic emission (AE) characteristics during the deformation and fracture of rock under the action of continuous heating and after high-temperature treatment. Using AE 3D positioning technology, the development and evolution of the internal thermal cracks and the time domain of AE signals in rock were analyzed. High-temperature treatment causes thermal damage to rock. Under the action of continuous heating, the phase characteristics of AE time series correspond to the five stages of rock thermal deformation and fracture, respectively: the micro-defect development stage, the threshold interval of rock micro-cracks, the crack initiation stage, the crack propagation stage, and the crack multistage propagation evolution. When the initial crack propagates, the crack initiation of the rock causes the AE signal to produce a sudden mutation change. Mechanical fraction characteristics during rock uniaxial compression after temperature treatment indicated that the decrease rate of the rock compressive strength, wave velocity, and elastic modulus are relatively large during uniaxial compression tests after high-temperature treatment. During the deformation and fracture of rock under loading, there is faster growth of AE counts and AE events, indicating an increase in the speed of rock deformation and fracture under loading. AE counts show obvious changes during the latter loading stages, whereas AE events show obvious changes during the loading process. The results obtained are valuable for rock thermal stability detection and evaluation in actual underground engineering.

Method and apparatus for the measurement of signals from radiation sensors

DOEpatents

De Geronimo, Gianluigi

2012-09-18

The preferred embodiments of the present invention include a device for measuring an ionizing event in a radiation sensor. The device can include a charge amplifier and a timing shaper. The charge amplifier receives a cathode signal and is configured to output an amplified cathode signal. The timing shaper is operatively connected to the charge amplifier to receive the amplified cathode signal. The timing shaper is configured to generate a first pulse in response to a beginning of the ionizing event and a second pulse in response to an end of the ionizing event. The first and second pulses are associated with a depth of interaction of the ionizing event and are generated in response to a slope of the amplified cathode signal changing.

Apparatus and method for detecting full-capture radiation events

DOEpatents

Odell, D.M.C.

1994-10-11

An apparatus and method are disclosed for sampling the output signal of a radiation detector and distinguishing full-capture radiation events from Compton scattering events. The output signal of a radiation detector is continuously sampled. The samples are converted to digital values and input to a discriminator where samples that are representative of events are identified. The discriminator transfers only event samples, that is, samples representing full-capture events and Compton events, to a signal processor where the samples are saved in a three-dimensional count matrix with time (from the time of onset of the pulse) on the first axis, sample pulse current amplitude on the second axis, and number of samples on the third axis. The stored data are analyzed to separate the Compton events from full-capture events, and the energy of the full-capture events is determined without having determined the energies of any of the individual radiation detector events. 4 figs.

Apparatus and method for detecting full-capture radiation events

DOEpatents

Odell, Daniel M. C.

1994-01-01

An apparatus and method for sampling the output signal of a radiation detector and distinguishing full-capture radiation events from Compton scattering events. The output signal of a radiation detector is continuously sampled. The samples are converted to digital values and input to a discriminator where samples that are representative of events are identified. The discriminator transfers only event samples, that is, samples representing full-capture events and Compton events, to a signal processor where the samples are saved in a three-dimensional count matrix with time (from the time of onset of the pulse) on the first axis, sample pulse current amplitude on the second axis, and number of samples on the third axis. The stored data are analyzed to separate the Compton events from full-capture events, and the energy of the full-capture events is determined without having determined the energies of any of the individual radiation detector events.

A novel regulation of IRS1 (insulin receptor substrate-1) expression following short term insulin administration

PubMed Central

2005-01-01

Reduced insulin-mediated glucose transport in skeletal muscle is a hallmark of the pathophysiology of T2DM (Type II diabetes mellitus). Impaired intracellular insulin signalling is implicated as a key underlying mechanism. Attention has focused on early signalling events such as defective tyrosine phosphorylation of IRS1 (insulin receptor substrate-1), a major target for the insulin receptor tyrosine kinase. This is required for normal induction of signalling pathways key to many of the metabolic actions of insulin. Conversely, increased serine/threonine phosphorylation of IRS1 following prolonged insulin exposure (or in obesity) reduces signalling capacity, partly by stimulating IRS1 degradation. We now show that IRS1 levels in human muscle are actually increased 3-fold following 1 h of hyperinsulinaemic euglycaemia. Similarly, transient induction of IRS1 (3-fold) in the liver or muscle of rodents occurs following feeding or insulin injection respectively. The induction by insulin is also observed in cell culture systems, although to a lesser degree, and is not due to reduced proteasomal targeting, increased protein synthesis or gene transcription. Elucidation of the mechanism by which insulin promotes IRS1 stability will permit characterization of the importance of this novel signalling event in insulin regulation of liver and muscle function. Impairment of this process would reduce IRS1 signalling capacity, thereby contributing to the development of hyperinsulinaemia/insulin resistance prior to the appearance of T2DM. PMID:16128672

Local auxin production underlies a spatially restricted neighbor-detection response in Arabidopsis

PubMed Central

Michaud, Olivier

2017-01-01

Competition for light triggers numerous developmental adaptations known as the “shade-avoidance syndrome” (SAS). Important molecular events underlying specific SAS responses have been identified. However, in natural environments light is often heterogeneous, and it is currently unknown how shading affecting part of a plant leads to local responses. To study this question, we analyzed upwards leaf movement (hyponasty), a rapid adaptation to neighbor proximity, in Arabidopsis. We show that manipulation of the light environment at the leaf tip triggers a hyponastic response that is restricted to the treated leaf. This response is mediated by auxin synthesized in the blade and transported to the petiole. Our results suggest that a strong auxin response in the vasculature of the treated leaf and auxin signaling in the epidermis mediate leaf elevation. Moreover, the analysis of an auxin-signaling mutant reveals signaling bifurcation in the control of petiole elongation versus hyponasty. Our work identifies a mechanism for a local shade response that may pertain to other plant adaptations to heterogeneous environments. PMID:28652343

An approach to source characterization of tremor signals associated with eruptions and lahars

NASA Astrophysics Data System (ADS)

Kumagai, Hiroyuki; Mothes, Patricia; Ruiz, Mario; Maeda, Yuta

2015-11-01

Tremor signals are observed in association with eruption activity and lahar descents. Reduced displacement ( D R) derived from tremor signals has been used to quantify tremor sources. However, tremor duration is not considered in D R, which makes it difficult to compare D R values estimated for different tremor episodes. We propose application of the amplitude source location (ASL) method to characterize the sources of tremor signals. We used this method to estimate the tremor source location and source amplitude from high-frequency (5-10 Hz) seismic amplitudes under the assumption of isotropic S-wave radiation. We considered the source amplitude to be the maximum value during tremor. We estimated the cumulative source amplitude ( I s) as the offset value of the time-integrated envelope of the vertical seismogram of tremor corrected for geometrical spreading and medium attenuation in the 5-10-Hz band. For eruption tremor signals, we also estimated the cumulative source pressure ( I p) from an infrasonic envelope waveform corrected for geometrical spreading. We studied these parameters of tremor signals associated with eruptions and lahars and explosion events at Tungurahua volcano, Ecuador. We identified two types of eruption tremor at Tungurahua: noise-like inharmonic waveforms and harmonic oscillatory signals. We found that I s increased linearly with increasing source amplitude for lahar tremor signals and explosion events, but I s increased exponentially with increasing source amplitude for inharmonic eruption tremor signals. The source characteristics of harmonic eruption tremor signals differed from those of inharmonic tremor signals. We found a linear relation between I s and I p for both explosion events and eruption tremor. Because I p may be proportional to the total mass involved during an eruption episode, this linear relation suggests that I s may be useful to quantify eruption size. The I s values we estimated for inharmonic eruption tremor were consistent with previous estimates of volumes of tephra fallout. The scaling relations among source parameters that we identified will contribute to our understanding of the dynamic processes associated with eruptions and lahars. This new approach is applicable in analyzing tremor sources in real time and may contribute to early assessment of the size of eruptions and lahars.

Plant defense induced in in vitro propagated banana (Musa paradisiaca) plantlets by Fusarium derived elicitors.

PubMed

Patel, Miral; Kothari, I L; Mohan, J S S

2004-07-01

Perception of microbial signal molecules is part of the strategy evolved by plants to survive attacks by potential pathogens. To gain a more complete understanding of the early signaling events involved in these responses, we used fungal components of Fusarium under in vitro condition and checked the rise in signal molecule, salicylic acid (SA), and marker enzymes in defense reactions against the pathogen. SA level increased by 21 folds in elicitor treated plantlets as compared to that of control plantlets and there was marked increase in phenylalanine ammonia-lyase(PAL), peroxidase(POX), polyphenol oxidase(PPO) along with higher total phenolic content. Present results indicated that use of fungal components had successfully induced systemic resistance in in vitro cultured banana plantlets.

Ethylene-Mediated Acclimations to Flooding Stress1

PubMed Central

Sasidharan, Rashmi; Voesenek, Laurentius A.C.J.

2015-01-01

Flooding is detrimental for plants, primarily because of restricted gas exchange underwater, which leads to an energy and carbohydrate deficit. Impeded gas exchange also causes rapid accumulation of the volatile ethylene in all flooded plant cells. Although several internal changes in the plant can signal the flooded status, it is the pervasive and rapid accumulation of ethylene that makes it an early and reliable flooding signal. Not surprisingly, it is a major regulator of several flood-adaptive plant traits. Here, we discuss these major ethylene-mediated traits, their functional relevance, and the recent progress in identifying the molecular and signaling events underlying these traits downstream of ethylene. We also speculate on the role of ethylene in postsubmergence recovery and identify several questions for future investigations. PMID:25897003

GPR30 Activation Opposes Estrogen-Dependent Uterine Growth via Inhibition of Stromal ERK1/2 and Estrogen Receptor Alpha (ERα) Phosphorylation Signals

PubMed Central

Gao, Fei; Ma, Xinghong; Ostmann, Alicia B.

2011-01-01

Although estradiol-17β (E2)-regulated early and late phase uterine responses have been well defined, the molecular mechanisms linking the phases remain poorly understood. We have previously shown that E2-regulated early signals mediate cross talk with estrogen receptor (ER)-α to elicit uterine late growth responses. G protein-coupled receptor (GPR30) has been implicated in early nongenomic signaling mediated by E2, although its role in E2-dependent uterine biology is unclear. Using selective activation of GPR30 by G-1, we show here a new function of GPR30 in regulating early signaling events, including the inhibition of ERK1/2 and ERα (Ser118) phosphorylation signals and perturbation of growth regulation under the direction of E2 in the mouse uterus. We observed that GPR30 primarily localizes in the uterine epithelial cells, and its activation alters gene expression and mediates inhibition of ERK1/2 and ERα (Ser118) phosphorylation signals in the stromal compartment, suggesting a paracrine signaling is involved. Importantly, viral-driven manipulation of GPR30 or pharmacological inhibition of ERK1/2 activation effectively alters E2-dependent uterine growth responses. Overall, GPR30 is a negative regulator of ERα-dependent uterine growth in response to E2. Our work has uncovered a novel GPR30-regulated inhibitory event, which may be physiologically relevant in both normal and pathological situations to negatively balance ERα-dependent uterine growth regulatory functions induced by E2. PMID:21303939

Methods for monitoring hydroacoustic events using direct and reflected T waves in the Indian Ocean

NASA Astrophysics Data System (ADS)

Hanson, Jeffrey A.; Bowman, J. Roger

2006-02-01

The recent installation of permanent, three-element hydrophone arrays in the Indian Ocean offshore Diego Garcia and Cape Leeuwin, Australia, provides an opportunity to study hydroacoustic sources in more detail than previously possible. We developed and applied methods for coherent processing of the array data, for automated association of signals detected at more than one array, and for source location using only direct arrivals and using signals reflected from coastlines and other bathymetric features. During the 286-day study, 4725 hydroacoustic events were defined and located in the Indian and Southern oceans. Events fall into two classes: tectonic earthquakes and ice-related noise. The tectonic earthquakes consist of mid-ocean ridge, trench, and intraplate earthquakes. Mid-ocean ridge earthquakes are the most common tectonic events and often occur in clusters along transform offsets. Hydroacoustic signal levels for earthquakes in a standard catalog suggest that the hydroacoustic processing threshold for ridge events is one magnitude below the seismic network. Fewer earthquakes are observed along the Java Trench than expected because the large bathymetric relief of the source region complicates coupling between seismic and hydroacoustic signals, leading to divergent signal characteristics at different stations. We located 1843 events along the Antarctic coast resulting from various ice noises, most likely thermal fracturing and ice ridge forming events. Reflectors of signals from earthquakes are observed along coastlines, the mid-Indian Ocean and Ninety East ridges, and other bathymetric features. Reflected signals are used as synthetic stations to reduce location uncertainty and to enable event location with a single station.

Jak2 FERM Domain Interaction with the Erythropoietin Receptor Regulates Jak2 Kinase Activity▿

PubMed Central

Funakoshi-Tago, Megumi; Pelletier, Stéphane; Moritake, Hiroshi; Parganas, Evan; Ihle, James N.

2008-01-01

Janus kinases are essential for signal transduction by a variety of cytokine receptors and when inappropriately activated can cause hematopoietic disorders and oncogenesis. Consequently, it can be predicted that the interaction of the kinases with receptors and the events required for activation are highly controlled. In a screen to identify phosphorylation events regulating Jak2 activity in EpoR signaling, we identified a mutant (Jak2-Y613E) which has the property of being constitutively activated, as well as an inactivating mutation (Y766E). Although no evidence was obtained to indicate that either site is phosphorylated in signaling, the consequences of the Y613E mutation are similar to those observed with recently described activating mutations in Jak2 (Jak2-V617F and Jak2-L611S). However, unlike the V617F or L611S mutant, the Y613E mutant requires the presence of the receptor but not Epo stimulation for activation and downstream signaling. The properties of the Jak2-Y613E mutant suggest that under normal conditions, Jak2 that is not associated with a receptor is locked into an inactive state and receptor binding through the FERM domain relieves steric constraints, allowing the potential to be activated with receptor engagement. PMID:18160720

Event Compression Using Recursive Least Squares Signal Processing.

DTIC Science & Technology

1980-07-01

decimation of the Burstl signal with and without all-pole prefiltering to reduce aliasing . Figures 3.32a-c and 3.33a-c show the same examples but with 4/1...to reduce aliasing , w~t found that it did not improve the quality of the event compressed signals . If filtering must be performed, all-pole filtering...A-AO89 785 MASSACHUSETTS IN T OF TECH CAMBRIDGE RESEARCH LAB OF--ETC F/B 17/9 EVENT COMPRESSION USING RECURSIVE LEAST SQUARES SIGNAL PROCESSI-ETC(t

System and method for generating micro-seismic events and characterizing properties of a medium with non-linear acoustic interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vu, Cung Khac; Nihei, Kurt; Johnson, Paul A.

2015-12-29

A method and system includes generating a first coded acoustic signal including pulses each having a modulated signal at a central frequency; and a second coded acoustic signal each pulse of which includes a modulated signal a central frequency of which is a fraction d of the central frequency of the modulated signal for the corresponding pulse in the first plurality of pulses. A receiver detects a third signal generated by a non-linear mixing process in the mixing zone and the signal is processed to extract the third signal to obtain an emulated micro-seismic event signal occurring at the mixingmore » zone; and to characterize properties of the medium or creating a 3D image of the properties of the medium, or both, based on the emulated micro-seismic event signal.« less

Useful Interplay Between Spontaneous ADR Reports and Electronic Healthcare Records in Signal Detection.

PubMed

Pacurariu, Alexandra C; Straus, Sabine M; Trifirò, Gianluca; Schuemie, Martijn J; Gini, Rosa; Herings, Ron; Mazzaglia, Giampiero; Picelli, Gino; Scotti, Lorenza; Pedersen, Lars; Arlett, Peter; van der Lei, Johan; Sturkenboom, Miriam C; Coloma, Preciosa M

2015-12-01

Spontaneous reporting systems (SRSs) remain the cornerstone of post-marketing drug safety surveillance despite their well-known limitations. Judicious use of other available data sources is essential to enable better detection, strengthening and validation of signals. In this study, we investigated the potential of electronic healthcare records (EHRs) to be used alongside an SRS as an independent system, with the aim of improving signal detection. A signal detection strategy, focused on a limited set of adverse events deemed important in pharmacovigilance, was performed retrospectively in two data sources-(1) the Exploring and Understanding Adverse Drug Reactions (EU-ADR) database network and (2) the EudraVigilance database-using data between 2000 and 2010. Five events were considered for analysis: (1) acute myocardial infarction (AMI); (2) bullous eruption; (3) hip fracture; (4) acute pancreatitis; and (5) upper gastrointestinal bleeding (UGIB). Potential signals identified in each system were verified using the current published literature. The complementarity of the two systems to detect signals was expressed as the percentage of the unilaterally identified signals out of the total number of confirmed signals. As a proxy for the associated costs, the number of signals that needed to be reviewed to detect one true signal (number needed to detect [NND]) was calculated. The relationship between the background frequency of the events and the capability of each system to detect signals was also investigated. The contribution of each system to signal detection appeared to be correlated with the background incidence of the events, being directly proportional to the incidence in EU-ADR and inversely proportional in EudraVigilance. EudraVigilance was particularly valuable in identifying bullous eruption and acute pancreatitis (71 and 42 % of signals were correctly identified from the total pool of known associations, respectively), while EU-ADR was most useful in identifying hip fractures (60 %). Both systems contributed reasonably well to identification of signals related to UGIB (45 % in EudraVigilance, 40 % in EU-ADR) but only fairly for signals related to AMI (25 % in EU-ADR, 20 % in EudraVigilance). The costs associated with detection of signals were variable across events; however, it was often more costly to detect safety signals in EU-ADR than in EudraVigilance (median NNDs: 7 versus 5). An EHR-based system may have additional value for signal detection, alongside already established systems, especially in the presence of adverse events with a high background incidence. While the SRS appeared to be more cost effective overall, for some events the costs associated with signal detection in the EHR might be justifiable.

Apparatus and method for processing Korotkov sounds. [for blood pressure measurement

NASA Technical Reports Server (NTRS)

Golden, D. P., Jr.; Hoffler, G. W.; Wolthuis, R. A. (Inventor)

1974-01-01

A Korotkov sound processor, used in a noninvasive automatic blood measuring system where the brachial artery is occluded by an inflatable cuff, is disclosed. The Korotkoff sound associated with the systolic event is determined when the ratio of the absolute value of a voltage signal, representing Korotkov sounds in the range of 18 to 26 Hz to a maximum absolute peak value of the unfiltered signals, first equals or exceeds a value of 0.45. Korotkov sound associated with the diastolic event is determined when a ratio of the voltage signal of the Korotkov sounds in the range of 40 to 60 Hz to the absolute peak value of such signals within a single measurement cycle first falls below a value of 0.17. The processor signals the occurrence of the systolic and diastolic events and these signals can be used to control a recorder to record pressure values for these events.

Unusual Signals Recorded by Ocean Bottom Seismometers in the Caldera of Deception Island Volcano: Biological Activity or Hydrothermally Generated Seismicity?

NASA Astrophysics Data System (ADS)

Bowman, D. C.; Wilcock, W. S.

2011-12-01

As part of an active source land-sea tomography experiment, ocean bottom seismometers (OBSs) were deployed at Deception Island Volcano, Antarctica, in January 2005. Following the tomography study, three OBSs were left for a month inside the flooded caldera and ten on the outer slopes of the volcano to record seismo-volcanic signals. The OBS sensor package included three-orthogonal 1-Hz geophones but no hydrophone. The OBSs were deployed in water depths of 125 to 143 m inside the caldera and at depths of 119 to 475 m on the volcano's flanks. Only two volcano-tectonic earthquakes and three long period events were recorded by the network. However, the OBSs inside the caldera recorded over 4,500 unusual seismic events. These were detected by only one station at a time and were completely absent from OBSs on the flank of the volcano and from land stations deployed on the island. The signals had a dominant frequency of 5 Hz and were one to ten seconds long. Event activity in the caldera was variable with the number of events per hour ranging from 0 up to 60 and the level of activity decreasing slightly over the study period. We categorize the signals into three types based on waveform characteristics. Type 1 events have an impulsive onset and last 1 to 2 s with characteristics that are consistent with the impulse response of a poorly coupled OBS. Type 2 events typically last 2 to 4 s and comprise a low amplitude initial arrival followed less than a second later by a more energetic second phase that looks a Type 1 event. Type 3 events last up to 10 s and have more complex waveforms that appear to comprise several arrivals of varying amplitudes. Type 1 events are similar to the 'fish-bump' signals reported from previous studies that attributed them to biological activity. The consistent timing and relative amplitudes of the two arrivals for Type 2 events are difficult to explain by animals randomly touching the OBSs. Type 3 events are quite similar in frequency, duration, and signal characteristics to long-period seismic events recorded by an onshore seismic array deployed in an earlier study at Deception Island. Particle motions suggest that Type 3 events may be surface waves while the particle motions for Type 1 and Type 2 events are ambiguous and unlike any signals recorded by land arrays at the volcano. Binomial tests of the event distribution show no significant changes in the rate of events with time of day that would be indicative of a biological source. Since the events are entirely absent in biologically productive waters outside the caldera, we postulate that they may be volcanic signals related to hydrothermal flow across the seafloor in the flooded caldera of Deception Island. Future OBS deployments at Deception Island should include a hydrophone to discriminate unambiguously between biological and volcanic signals.

Pulse oximetry recorded from the Phone Oximeter for detection of obstructive sleep apnea events with and without oxygen desaturation in children.

PubMed

Garde, Ainara; Dehkordi, Parastoo; Wensley, David; Ansermino, J Mark; Dumont, Guy A

2015-01-01

Obstructive sleep apnea (OSA) disrupts normal ventilation during sleep and can lead to serious health problems in children if left untreated. Polysomnography, the gold standard for OSA diagnosis, is resource intensive and requires a specialized laboratory. Thus, we proposed to use the Phone Oximeter™, a portable device integrating pulse oximetry with a smartphone, to detect OSA events. As a proportion of OSA events occur without oxygen desaturation (defined as SpO2 decreases ≥ 3%), we suggest combining SpO2 and pulse rate variability (PRV) analysis to identify all OSA events and provide a more detailed sleep analysis. We recruited 160 children and recorded pulse oximetry consisting of SpO2 and plethysmography (PPG) using the Phone Oximeter™, alongside standard polysomnography. A sleep technician visually scored all OSA events with and without oxygen desaturation from polysomnography. We divided pulse oximetry signals into 1-min signal segments and extracted several features from SpO2 and PPG analysis in the time and frequency domain. Segments with OSA, especially the ones with oxygen desaturation, presented greater SpO2 variability and modulation reflected in the spectral domain than segments without OSA. Segments with OSA also showed higher heart rate and sympathetic activity through the PRV analysis relative to segments without OSA. PRV analysis was more sensitive than SpO2 analysis for identification of OSA events without oxygen desaturation. Combining SpO2 and PRV analysis enhanced OSA event detection through a multiple logistic regression model. The area under the ROC curve increased from 81% to 87%. Thus, the Phone Oximeter™ might be useful to monitor sleep and identify OSA events with and without oxygen desaturation at home.

Inhibition of VEGF Signaling Reduces Diabetes-Exacerbated Brain Swelling, but Not Infarct Size, in Large Cerebral Infarction in Mice.

PubMed

Kim, Eunhee; Yang, Jiwon; Park, Keun Woo; Cho, Sunghee

2017-12-30

In light of repeated translational failures with preclinical neuroprotection-based strategies, this preclinical study reevaluates brain swelling as an important pathological event in diabetic stroke and investigates underlying mechanism of the comorbidity-enhanced brain edema formation. Type 2 (mild), type 1 (moderate), and mixed type 1/2 (severe) diabetic mice were subjected to transient focal ischemia. Infarct volume, brain swelling, and IgG extravasation were assessed at 3 days post-stroke. Expression of vascular endothelial growth factor (VEGF)-A, endothelial-specific molecule-1 (Esm1), and the VEGF receptor 2 (VEGFR2) was determined in the ischemic brain. Additionally, SU5416, a VEGFR2 inhibitor, was treated in the type 1/2 diabetic mice, and stroke outcomes were determined. All diabetic groups displayed bigger infarct volume and brain swelling compared to nondiabetic mice, and the increased swelling was disproportionately larger relative to infarct enlargement. Diabetic conditions significantly increased VEGF-A, Esm1, and VEGFR2 expressions in the ischemic brain compared to nondiabetic mice. Notably, in diabetic mice, VEGFR2 mRNA levels were positively correlated with brain swelling, but not with infarct volume. Treatment with SU5416 in diabetic mice significantly reduced brain swelling. The study shows that brain swelling is a predominant pathological event in diabetic stroke and that an underlying event for diabetes-enhanced brain swelling includes the activation of VEGF signaling. This study suggests consideration of stroke therapies aiming at primarily reducing brain swelling for subjects with diabetes.

Using natural archives to detect climate and environmental tipping points in the Earth System

NASA Astrophysics Data System (ADS)

Thomas, Zoë A.

2016-11-01

'Tipping points' in the Earth system are characterised by a nonlinear response to gradual forcing, and may have severe and wide-ranging impacts. Many abrupt events result from simple underlying system dynamics termed 'critical transitions' or 'bifurcations'. One of the best ways to identify and potentially predict threshold behaviour in the climate system is through analysis of natural ('palaeo') archives. Specifically, on the approach to a tipping point, early warning signals can be detected as characteristic fluctuations in a time series as a system loses stability. Testing whether these early warning signals can be detected in highly complex real systems is a key challenge, since much work is either theoretical or only tested with simple models. This is particularly problematic in palaeoclimate and palaeoenvironmental records with low resolution, non-equidistant data, which can limit accurate analysis. Here, a range of different datasets are examined to explore generic rules that can be used to detect such dramatic events. A number of key criteria are identified to be necessary for the reliable identification of early warning signals in natural archives, most crucially, the need for a low-noise record of sufficient data length, resolution and accuracy. A deeper understanding of the underlying system dynamics is required to inform the development of more robust system-specific indicators, or to indicate the temporal resolution required, given a known forcing. This review demonstrates that time series precursors from natural archives provide a powerful means of forewarning tipping points within the Earth System.

From Multi-Sensors Observations Towards Cross-Disciplinary Study of Pre-Earthquake Signals. What have We Learned from the Tohoku Earthquake?

NASA Technical Reports Server (NTRS)

Ouzounov, D.; Pulinets, S.; Papadopoulos, G.; Kunitsyn, V.; Nesterov, I.; Hayakawa, M.; Mogi, K.; Hattori, K.; Kafatos, M.; Taylor, P.

2012-01-01

The lessons we have learned from the Great Tohoku EQ (Japan, 2011) how this knowledge will affect our future observation and analysis is the main focus of this presentation.We present multi-sensors observations and multidisciplinary research in our investigation of phenomena preceding major earthquakes. These observations revealed the existence of atmospheric and ionospheric phenomena occurring prior to theM9.0 Tohoku earthquake of March 11, 2011, which indicates s new evidence of a distinct coupling between the lithosphere and atmosphere/ionosphere, as related to underlying tectonic activity. Similar results have been reported before the catastrophic events in Chile (M8.8, 2010), Italy (M6.3, 2009) and Sumatra (M9.3, 2004). For the Tohoku earthquake, our analysis shows a synergy between several independent observations characterizing the state of the lithosphere /atmosphere coupling several days before the onset of the earthquakes, namely: (i) Foreshock sequence change (rate, space and time); (ii) Outgoing Long wave Radiation (OLR) measured at the top of the atmosphere; and (iii) Anomalous variations of ionospheric parameters revealed by multi-sensors observations. We are presenting a cross-disciplinary analysis of the observed pre-earthquake anomalies and will discuss current research in the detection of these signals in Japan. We expect that our analysis will shed light on the underlying physics of pre-earthquake signals associated with some of the largest earthquake events

Real-time measurements, rare events and photon economics

NASA Astrophysics Data System (ADS)

Jalali, B.; Solli, D. R.; Goda, K.; Tsia, K.; Ropers, C.

2010-07-01

Rogue events otherwise known as outliers and black swans are singular, rare, events that carry dramatic impact. They appear in seemingly unconnected systems in the form of oceanic rogue waves, stock market crashes, evolution, and communication systems. Attempts to understand the underlying dynamics of such complex systems that lead to spectacular and often cataclysmic outcomes have been frustrated by the scarcity of events, resulting in insufficient statistical data, and by the inability to perform experiments under controlled conditions. Extreme rare events also occur in ultrafast physical sciences where it is possible to collect large data sets, even for rare events, in a short time period. The knowledge gained from observing rare events in ultrafast systems may provide valuable insight into extreme value phenomena that occur over a much slower timescale and that have a closer connection with human experience. One solution is a real-time ultrafast instrument that is capable of capturing singular and randomly occurring non-repetitive events. The time stretch technology developed during the past 13 years is providing a powerful tool box for reaching this goal. This paper reviews this technology and discusses its use in capturing rogue events in electronic signals, spectroscopy, and imaging. We show an example in nonlinear optics where it was possible to capture rare and random solitons whose unusual statistical distribution resemble those observed in financial markets. The ability to observe the true spectrum of each event in real time has led to important insight in understanding the underlying process, which in turn has made it possible to control soliton generation leading to improvement in the coherence of supercontinuum light. We also show a new class of fast imagers which are being considered for early detection of cancer because of their potential ability to detect rare diseased cells (so called rogue cells) in a large population of healthy cells.

New insights into pioneer root xylem development: evidence obtained from Populus trichocarpa plants grown under field conditions

PubMed Central

Bagniewska-Zadworna, Agnieszka; Arasimowicz-Jelonek, Magdalena; Smoliński, Dariusz J.; Stelmasik, Agnieszka

2014-01-01

Background and Aims Effective programmed xylogenesis is critical to the structural framework of the plant root system and its central role in the acquisition and long-distance transport of water and nutrients. The process of xylem differentiation in pioneer roots under field conditions is poorly understood. In this study it is hypothesized that xylogenesis, an example of developmental programmed cell death (PCD), in the roots of woody plants demonstrates a clearly defined sequence of events resulting in cell death. A comprehensive analysis was therefore undertaken to identify the stages of xylogenesis in pioneer roots from procambial cells to fully functional vessels with lignified cell walls and secondary cell wall thickenings. Methods Xylem differentiation was monitored in the pioneer roots of Populus trichocarpa at the cytological level using rhizotrons under field conditions. Detection and localization of the signalling molecule nitric oxide (NO) and hydrogen peroxide (H2O2) was undertaken and a detailed examination of nuclear changes during xylogenesis was conducted. In addition, analyses of the expression of genes involved in secondary cell wall synthesis were performed in situ. Key Results The primary event in initially differentiating tracheary elements (TEs) was a burst of NO in thin-walled cells, followed by H2O2 synthesis and the appearance of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling)-positive nuclei. The first changes in nuclear structure were observed in the early stages of xylogenesis of pioneer roots, prior to lignification; however, the nucleus was detectable under transmission electron microscopy in differentiating cells until the stage at which vacuole integrity was maintained, indicating that their degradation was slow and prolonged. The subsequent sequence of events involved secondary cell wall formation and autophagy. Potential gene markers from the cinnamyl alcohol dehydrogenase (CAD) gene family that were related to secondary wall synthesis were associated with primary xylogenesis, showing clear expression in cells that undergo differentiation into TEs and in the thin-walled cells adjacent to the xylem pole. Conclusions The early events of TE formation during pioneer root development are described, together with the timing of xylogenesis from signalling via NO, through secondary cell wall synthesis and autophagy events that are initiated long before lignification. This is the first work describing experiments conducted in planta on roots under field conditions demonstrating that the process of xylogenesis in vivo might be gradual and complex. PMID:24812251

Mechanisms of JAK/STAT pathway negative regulation by the short coreceptor Eye Transformer/Latran.

PubMed

Fisher, Katherine H; Stec, Wojciech; Brown, Stephen; Zeidler, Martin P

2016-02-01

Transmembrane receptors interact with extracellular ligands to transduce intracellular signaling cascades, modulate target gene expression, and regulate processes such as proliferation, apoptosis, differentiation, and homeostasis. As a consequence, aberrant signaling events often underlie human disease. Whereas the vertebrate JAK/STAT signaling cascade is transduced via multiple receptor combinations, the Drosophila pathway has only one full-length signaling receptor, Domeless (Dome), and a single negatively acting receptor, Eye Transformer/Latran (Et/Lat). Here we investigate the molecular mechanisms underlying Et/Lat activity. We demonstrate that Et/Lat negatively regulates the JAK/STAT pathway activity and can bind to Dome, thus reducing Dome:Dome homodimerization by creating signaling-incompetent Dome:Et/Lat heterodimers. Surprisingly, we find that Et/Lat is able to bind to both JAK and STAT92E but, despite the presence of putative cytokine-binding motifs, does not detectably interact with pathway ligands. We find that Et/Lat is trafficked through the endocytic machinery for lysosomal degradation but at a much slower rate than Dome, a difference that may enhance its ability to sequester Dome into signaling-incompetent complexes. Our data offer new insights into the molecular mechanism and regulation of Et/Lat in Drosophila that may inform our understanding of how short receptors function in other organisms. © 2016 Fisher et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Analysis of low-frequency seismic signals generated during a multiple-iceberg calving event at Jakobshavn Isbræ, Greenland

USGS Publications Warehouse

Walter, Fabian; Amundson, Jason M.; O'Neel, Shad; Truffer, Martin; Fahnestock, Mark; Fricker, Helen A.

2012-01-01

We investigated seismic signals generated during a large-scale, multiple iceberg calving event that occurred at Jakobshavn Isbræ, Greenland, on 21 August 2009. The event was recorded by a high-rate time-lapse camera and five broadband seismic stations located within a few hundred kilometers of the terminus. During the event two full-glacier-thickness icebergs calved from the grounded (or nearly grounded) terminus and immediately capsized; the second iceberg to calve was two to three times smaller than the first. The individual calving and capsize events were well-correlated with the radiation of low-frequency seismic signals (<0.1 Hz) dominated by Love and Rayleigh waves. In agreement with regional records from previously published ‘glacial earthquakes’, these low-frequency seismic signals had maximum power and/or signal-to-noise ratios in the 0.05–0.1 Hz band. Similarly, full waveform inversions indicate that these signals were also generated by horizontal single forces acting at the glacier terminus. The signals therefore appear to be local manifestations of glacial earthquakes, although the magnitudes of the signals (twice-time integrated force histories) were considerably smaller than previously reported glacial earthquakes. We thus speculate that such earthquakes may be a common, if not pervasive, feature of all full-glacier-thickness calving events from grounded termini. Finally, a key result from our study is that waveform inversions performed on low-frequency, calving-generated seismic signals may have only limited ability to quantitatively estimate mass losses from calving. In particular, the choice of source time function has little impact on the inversion but dramatically changes the earthquake magnitude. Accordingly, in our analysis, it is unclear whether the smaller or larger of the two calving icebergs generated a larger seismic signal.

Hunting the Dark Matter with DEAP/CLEAN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giuliani, F.

2010-02-10

The potential of the DEAP/CLEAN program for direct Dark Matter detection to test various dark matter models is illustrated. The scintillation pulse of a noble liquid like Argon or Neon has two well distinguished time constants allowing a very reliable correlation between pulse shape and type of event. This pulse shape discrimination already provides the power of rejecting a background10{sup 8}-10{sup 9} times larger than the signal. MiniCLEAN, a 500 kg LAr detector, is currently under construction, and a 3.6 ton detector, DEAP-3600, under development.

Processing circuitry for single channel radiation detector

NASA Technical Reports Server (NTRS)

Holland, Samuel D. (Inventor); Delaune, Paul B. (Inventor); Turner, Kathryn M. (Inventor)

2009-01-01

Processing circuitry is provided for a high voltage operated radiation detector. An event detector utilizes a comparator configured to produce an event signal based on a leading edge threshold value. A preferred event detector does not produce another event signal until a trailing edge threshold value is satisfied. The event signal can be utilized for counting the number of particle hits and also for controlling data collection operation for a peak detect circuit and timer. The leading edge threshold value is programmable such that it can be reprogrammed by a remote computer. A digital high voltage control is preferably operable to monitor and adjust high voltage for the detector.

Application of temporal moments and other signal processing algorithms to analysis of ultrasonic signals through melting wax

DOE PAGES

Lau, Sarah J.; Moore, David G.; Stair, Sarah L.; ...

2016-01-01

Ultrasonic analysis is being explored as a way to capture events during melting of highly dispersive wax. Typical events include temperature changes in the material, phase transition of the material, surface flows and reformations, and void filling as the material melts. Melt tests are performed with wax to evaluate the usefulness of different signal processing algorithms in capturing event data. Several algorithm paths are being pursued. The first looks at changes in the velocity of the signal through the material. This is only appropriate when the changes from one ultrasonic signal to the next can be represented by a linearmore » relationship, which is not always the case. The second tracks changes in the frequency content of the signal. The third algorithm tracks changes in the temporal moments of a signal over a full test. This method does not require that the changes in the signal be represented by a linear relationship, but attaching changes in the temporal moments to physical events can be difficult. This study describes the algorithm paths applied to experimental data from ultrasonic signals as wax melts and explores different ways to display the results.« less

Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes*

PubMed Central

Collins, John A.; Wood, Scott T.; Nelson, Kimberly J.; Rowe, Meredith A.; Carlson, Cathy S.; Chubinskaya, Susan; Poole, Leslie B.; Furdui, Cristina M.; Loeser, Richard F.

2016-01-01

Oxidative stress-mediated post-translational modifications of redox-sensitive proteins are postulated as a key mechanism underlying age-related cellular dysfunction and disease progression. Peroxiredoxins (PRX) are critical intracellular antioxidants that also regulate redox signaling events. Age-related osteoarthritis is a common form of arthritis that has been associated with mitochondrial dysfunction and oxidative stress. The objective of this study was to determine the effect of aging and oxidative stress on chondrocyte intracellular signaling, with a specific focus on oxidation of cytosolic PRX2 and mitochondrial PRX3. Menadione was used as a model to induce cellular oxidative stress. Compared with chondrocytes isolated from young adult humans, chondrocytes from older adults exhibited higher levels of PRX1–3 hyperoxidation basally and under conditions of oxidative stress. Peroxiredoxin hyperoxidation was associated with inhibition of pro-survival Akt signaling and stimulation of pro-death p38 signaling. These changes were prevented in cultured human chondrocytes by adenoviral expression of catalase targeted to the mitochondria (MCAT) and in cartilage explants from MCAT transgenic mice. Peroxiredoxin hyperoxidation was observed in situ in human cartilage sections from older adults and in osteoarthritic cartilage. MCAT transgenic mice exhibited less age-related osteoarthritis. These findings demonstrate that age-related oxidative stress can disrupt normal physiological signaling and contribute to osteoarthritis and suggest peroxiredoxin hyperoxidation as a potential mechanism. PMID:26797130

Data Mining of the Public Version of the FDA Adverse Event Reporting System

PubMed Central

Sakaeda, Toshiyuki; Tamon, Akiko; Kadoyama, Kaori; Okuno, Yasushi

2013-01-01

The US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS, formerly AERS) is a database that contains information on adverse event and medication error reports submitted to the FDA. Besides those from manufacturers, reports can be submitted from health care professionals and the public. The original system was started in 1969, but since the last major revision in 1997, reporting has markedly increased. Data mining algorithms have been developed for the quantitative detection of signals from such a large database, where a signal means a statistical association between a drug and an adverse event or a drug-associated adverse event, including the proportional reporting ratio (PRR), the reporting odds ratio (ROR), the information component (IC), and the empirical Bayes geometric mean (EBGM). A survey of our previous reports suggested that the ROR provided the highest number of signals, and the EBGM the lowest. Additionally, an analysis of warfarin-, aspirin- and clopidogrel-associated adverse events suggested that all EBGM-based signals were included in the PRR-based signals, and also in the IC- or ROR-based ones, and that the PRR- and IC-based signals were in the ROR-based ones. In this article, the latest information on this area is summarized for future pharmacoepidemiological studies and/or pharmacovigilance analyses. PMID:23794943

Eolian Signal of the Onset of the Late Paleozoic Ice Age in North America Re-Deposited and Preserved As Paleo-Cave Sediments, Southwestern Colorado, U.S.a.

NASA Astrophysics Data System (ADS)

Evans, J. E.; Soreghan, M. J.

2014-12-01

The Molas Formation is a loessite consisting of reddish silt of Early Pennsylvanian (Bashkirian) age. U-Pb age spectra of accessory zircons indicate long-distance (>2000 km) transport from the Grenville province in northeastern North America plus sources from the peri-Gondwanan terranes in southeastern North America and local sources in the Ancestral Rocky Mountains uplift. These eolian sediments formed a blanket deposit <30 m thick above a paleokarst landscape in southwestern Colorado, infilling solution valleys and burying karst towers developed on the underlying Mississippian (Tournaisian-Visean) Leadville Limestone. The loessite is an eolian signal for the probable onset of glaciation at multiple locations in tectonically uplifted mountainous areas in North America. However, the loessite is easily eroded and has low preservation potential. Prior to lithification, significant amounts of the loess were remobilized and transported into the underlying karst system. As paleo-cave deposits, encased in limestone and dolostone, the silt-rich deposits have a higher preservation potential, and the eolian signal of the onset of the Late Paleozoic Ice Age in North America is still recognizable. However, the following signal modification processes need to be understood: (1) source area weathering and pedogenesis; (2) land-atmosphere transfer processes; (3) deposition effects of paleotopography, vegetation and moisture conditions, and infiltration into open fractures and/or the matrix of colluvium; (4) remobilization by surface runoff into open fractures and/or groundwater piping/sapping processes in loess soils; (5) transport into vadose and phreatic karst passageways by episodic ("streamflood") hydrologic events, forming event deposits (debrites, inundites, and jointites); (6) breakout dome collapse (forming interbedded cave sediments, karst breccias, and speleothems); (7) lithification and diagenesis; (8) post-lithification modification including pervasive hydrothermal mineralization; and (9) correctly recognizing the age of the signal.

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

PubMed

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

2012-10-05

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

Long-period events and tremor at Popocatepetl volcano (1994-2000) and their broadband characteristics

USGS Publications Warehouse

Arciniega-Ceballos, A.; Chouet, B.; Dawson, P.

2003-01-01

Following an initial phreatic eruption on 21 December 1994, activity at Popocatepetl has been dominated by fumarolic emissions interspersed with more energetic emissions of ashes and gases. A phase of repetitive dome-building and dome-destroying episodes began in March 1996 and is still ongoing at present. We describe the long-period (LP) seismicity accompanying eruptive activity at Popocatepetl from December 1994 through May 2000, using data from a three-component broadband seismometer located 5 km from the summit crater. The broadband records display a variety of signals, with periods ranging in the band 0.04-90 s. Long-period events and tremor with typical dominant periods in the range 0.3-2.0 s are the most characteristic signals observed at Popocatepetl. These signals appear to reflect volumetric sources driven by pressure fluctuations associated with the unsteady transport of gases beneath the crater. Very-long-period (VLP) signals are also observed in association with LP events and tremor. The VLP signals which accompany LP events display Ricker-like wavelets with periods near 36 s, whereas VLP signals associated with tremor waveforms typically show sustained oscillations at periods ranging up to 90 s. The spectra and particle motion patterns remain similar from event to event for the majority of LP and tremor signals analyzed during the time span of this study, suggesting a repeated, non-destructive activation of a common source. Hypocenters determined by phase pick analyses of selected LP events recorded by the seven-station, permanent Popocatepetl short-period network suggest that the majority of these events are confined to a source region in the top 1.5 km below the crater floor. The repetitive occurrences of VLP signals with closely matched waveform characteristics are consistent with a non-destructive reactivation of at least two sources. One source appears to coincide with the main source region of LP seismicity, whereas the second is a deeper source whose activity appears to be intimately linked with episodes of monochromatic tremor.

Realistic training scenario simulations and simulation techniques

DOEpatents

Dunlop, William H.; Koncher, Tawny R.; Luke, Stanley John; Sweeney, Jerry Joseph; White, Gregory K.

2017-12-05

In one embodiment, a system includes a signal generator operatively coupleable to one or more detectors; and a controller, the controller being both operably coupled to the signal generator and configured to cause the signal generator to: generate one or more signals each signal being representative of at least one emergency event; and communicate one or more of the generated signal(s) to a detector to which the signal generator is operably coupled. In another embodiment, a method includes: receiving data corresponding to one or more emergency events; generating at least one signal based on the data; and communicating the generated signal(s) to a detector.

Optimal filter parameters for low SNR seismograms as a function of station and event location

NASA Astrophysics Data System (ADS)

Leach, Richard R.; Dowla, Farid U.; Schultz, Craig A.

1999-06-01

Global seismic monitoring requires deployment of seismic sensors worldwide, in many areas that have not been studied or have few useable recordings. Using events with lower signal-to-noise ratios (SNR) would increase the amount of data from these regions. Lower SNR events can add significant numbers to data sets, but recordings of these events must be carefully filtered. For a given region, conventional methods of filter selection can be quite subjective and may require intensive analysis of many events. To reduce this laborious process, we have developed an automated method to provide optimal filters for low SNR regional or teleseismic events. As seismic signals are often localized in frequency and time with distinct time-frequency characteristics, our method is based on the decomposition of a time series into a set of subsignals, each representing a band with f/Δ f constant (constant Q). The SNR is calculated on the pre-event noise and signal window. The band pass signals with high SNR are used to indicate the cutoff filter limits for the optimized filter. Results indicate a significant improvement in SNR, particularly for low SNR events. The method provides an optimum filter which can be immediately applied to unknown regions. The filtered signals are used to map the seismic frequency response of a region and may provide improvements in travel-time picking, azimuth estimation, regional characterization, and event detection. For example, when an event is detected and a preliminary location is determined, the computer could automatically select optimal filter bands for data from non-reporting stations. Results are shown for a set of low SNR events as well as 379 regional and teleseismic events recorded at stations ABKT, KIV, and ANTO in the Middle East.

Sounds can boost the awareness of visual events through attention without cross-modal integration.

PubMed

Pápai, Márta Szabina; Soto-Faraco, Salvador

2017-01-31

Cross-modal interactions can lead to enhancement of visual perception, even for visual events below awareness. However, the underlying mechanism is still unclear. Can purely bottom-up cross-modal integration break through the threshold of awareness? We used a binocular rivalry paradigm to measure perceptual switches after brief flashes or sounds which, sometimes, co-occurred. When flashes at the suppressed eye coincided with sounds, perceptual switches occurred the earliest. Yet, contrary to the hypothesis of cross-modal integration, this facilitation never surpassed the assumption of probability summation of independent sensory signals. A follow-up experiment replicated the same pattern of results using silent gaps embedded in continuous noise, instead of sounds. This manipulation should weaken putative sound-flash integration, although keep them salient as bottom-up attention cues. Additional results showed that spatial congruency between flashes and sounds did not determine the effectiveness of cross-modal facilitation, which was again not better than probability summation. Thus, the present findings fail to fully support the hypothesis of bottom-up cross-modal integration, above and beyond the independent contribution of two transient signals, as an account for cross-modal enhancement of visual events below level of awareness.

MicroRNA-Directed Cancer Therapies: Implications in Melanoma Intervention.

PubMed

Thyagarajan, Anita; Shaban, Ahmed; Sahu, Ravi Prakash

2018-01-01

Acquired tumor resistance to cancer therapies poses major challenges in the treatment of cancers including melanoma. Among several signaling pathways or factors that affect neocarcinogenesis, cancer progression, and therapies, altered microRNAs (miRNAs) expression has been identified as a crucial player in modulating the key pathways governing these events. While studies in the miRNA field have grown exponentially in the last decade, much remains to be discovered, particularly with respect to their roles in cancer therapies. Since immune and nonimmune signaling cascades prevail in cancers, identification and evaluation of miRNAs, their molecular mechanisms and cellular targets involved in the underlying development of cancers, and acquired therapeutic resistance would help in devising new strategies for the prognosis, treatment, and an early detection of recurrence. Importantly, in-depth validation of miRNA-targeted molecular events could lead to the development of accurate progression-risk biomarkers, improved effectiveness, and improved patient responses to standard therapies. The current review focuses on the roles of miRNAs with recent updates on regulated cell cycle and proliferation, immune responses, oncogenic/epigenetic signaling pathways, invasion, metastasis, and apoptosis, with broader attention paid to melanomagenesis and melanoma therapies. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Mitochondrial flashes: From indicator characterization to in vivo imaging.

PubMed

Wang, Wang; Zhang, Huiliang; Cheng, Heping

2016-10-15

Mitochondrion is an organelle critically responsible for energy production and intracellular signaling in eukaryotic cells and its dysfunction often accompanies and contributes to human disease. Superoxide is the primary reactive oxygen species (ROS) produced in mitochondria. In vivo detection of superoxide has been a challenge in biomedical research. Here we describe the methods used to characterize a circularly permuted yellow fluorescent protein (cpYFP) as a biosensor for mitochondrial superoxide and pH dynamics. In vitro characterization reveals the high selectivity of cpYFP to superoxide over other ROS species and its dual sensitivity to pH. Confocal and two-photon imaging in conjunction with transgenic expression of the biosensor cpYFP targeted to the mitochondrial matrix detects mitochondrial flash events in living cells, perfused intact hearts, and live animals. The mitochondrial flashes are discrete and stochastic single mitochondrial events triggered by transient mitochondrial permeability transition (tMPT) and composed of a bursting superoxide signal and a transient alkalization signal. The real-time monitoring of single mitochondrial flashes provides a unique tool to study the integrated dynamism of mitochondrial respiration, ROS production, pH regulation and tMPT kinetics under diverse physiological and pathophysiological conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Lnk regulates integrin αIIbβ3 outside-in signaling in mouse platelets, leading to stabilization of thrombus development in vivo

PubMed Central

Takizawa, Hitoshi; Nishimura, Satoshi; Takayama, Naoya; Oda, Atsushi; Nishikii, Hidekazu; Morita, Yohei; Kakinuma, Sei; Yamazaki, Satoshi; Okamura, Satoshi; Tamura, Noriko; Goto, Shinya; Sawaguchi, Akira; Manabe, Ichiro; Takatsu, Kiyoshi; Nakauchi, Hiromitsu; Takaki, Satoshi; Eto, Koji

2009-01-01

The nature of the in vivo cellular events underlying thrombus formation mediated by platelet activation remains unclear because of the absence of a modality for analysis. Lymphocyte adaptor protein (Lnk; also known as Sh2b3) is an adaptor protein that inhibits thrombopoietin-mediated signaling, and as a result, megakaryocyte and platelet counts are elevated in Lnk–/– mice. Here we describe an unanticipated role for Lnk in stabilizing thrombus formation and clarify the activities of Lnk in platelets transduced through integrin αIIbβ3–mediated outside-in signaling. We equalized platelet counts in wild-type and Lnk–/– mice by using genetic depletion of Lnk and BM transplantation. Using FeCl3- or laser-induced injury and in vivo imaging that enabled observation of single platelet behavior and the multiple steps in thrombus formation, we determined that Lnk is an essential contributor to the stabilization of developing thrombi within vessels. Lnk–/– platelets exhibited a reduced ability to fully spread on fibrinogen and mediate clot retraction, reduced tyrosine phosphorylation of the β3 integrin subunit, and reduced binding of Fyn to integrin αIIbβ3. These results provide new insight into the mechanism of αIIbβ3-based outside-in signaling, which appears to be coordinated in platelets by Lnk, Fyn, and integrins. Outside-in signaling modulators could represent new therapeutic targets for the prevention of cardiovascular events. PMID:20038804

Effect Of Simulated Microgravity On Activated T Cell Gene Transcription

NASA Technical Reports Server (NTRS)

Morrow, Maureen A.

2003-01-01

Studies of T lymphocytes under the shear stress environment of clinorotation have demonstrated an inhibition of activation in response to TCR mediated signaling. These results mimic those observed during space flight. This work investigates the molecular signaling events of T lymphocyte activation with clinorotation. Purified human T lymphocytes and the T cell clone Jurkat exhibit an uncoupling of signaling as mediated through the TCR. Activation of the transcription factor AP-1 is inhibited while activation of NFAT occurs. NFAT dephosphorylation and activation is dependent on sustained Ca(++) influx. Alternatively, AP-1, which consists of two transcription factors, jun and fos, is activated by PKC and Ras mediated pathways. TCR signaling is known to be dependent on cytoskeletal rearrangements, in particular, raft aggregation is critical. Raft aggregation, as mediated through GM, crosslinking, overcomes the inhibition of T lymphocyte activation with clinorotation, indicating that the block is occurring upstream of raft aggregation. Clinorotation is shown to have an effect similar to a weak TCR signal.

High gain signal averaged electrocardiogram combined with 24 hour monitoring in patients early after myocardial infarction for bedside prediction of arrhythmic events.

PubMed Central

Cripps, T; Bennett, E D; Camm, A J; Ward, D E

1988-01-01

The value of the high gain, signal averaged electrocardiogram combined with 24 hour electrocardiographic monitoring in the prediction of arrhythmic events was assessed in 159 patients in the first week after myocardial infarction. Eleven patients (7%) suffered arrhythmic events during a mean (SD) of 12 (6) months of follow up (range 2-22, median 13 months). The combination of high gain, signal averaged electrocardiography and 24 hour electrocardiographic monitoring was more accurate than either technique alone or than clinical information collected during admission in predicting these events. The combination identified a high risk group of 13 (8%) patients, with an arrhythmic event rate of 62% and a low risk group with an event rate of 2%. The combination of high gain, signal averaged electrocardiography and 24 hour electrocardiographic monitoring in the first week after myocardial infarction provides a rapid, cheap, and non-invasive bedside method for the prediction of arrhythmias. PMID:3179133

Event sequence detector

NASA Technical Reports Server (NTRS)

Hanna, M. F. (Inventor)

1973-01-01

An event sequence detector is described with input units, each associated with a row of bistable elements arranged in an array of rows and columns. The detector also includes a shift register which is responsive to clock pulses from any of the units to sequentially provide signals on its output lines each of which is connected to the bistable elements in a corresponding column. When the event-indicating signal is received by an input unit it provides a clock pulse to the shift register to provide the signal on one of its output lines. The input unit also enables all its bistable elements so that the particular element in the column supplied with the signal from the register is driven to an event-indicating state.

Climate change, extreme weather events, and us health impacts: what can we say?

PubMed

Mills, David M

2009-01-01

Address how climate change impacts on a group of extreme weather events could affect US public health. A literature review summarizes arguments for, and evidence of, a climate change signal in select extreme weather event categories, projections for future events, and potential trends in adaptive capacity and vulnerability in the United States. Western US wildfires already exhibit a climate change signal. The variability within hurricane and extreme precipitation/flood data complicates identifying a similar climate change signal. Health impacts of extreme events are not equally distributed and are very sensitive to a subset of exceptional extreme events. Cumulative uncertainty in forecasting climate change driven characteristics of extreme events and adaptation prevents confidently projecting the future health impacts from hurricanes, wildfires, and extreme precipitation/floods in the United States attributable to climate change.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lau, Sarah J.; Moore, David G.; Stair, Sarah L.

Ultrasonic analysis is being explored as a way to capture events during melting of highly dispersive wax. Typical events include temperature changes in the material, phase transition of the material, surface flows and reformations, and void filling as the material melts. Melt tests are performed with wax to evaluate the usefulness of different signal processing algorithms in capturing event data. Several algorithm paths are being pursued. The first looks at changes in the velocity of the signal through the material. This is only appropriate when the changes from one ultrasonic signal to the next can be represented by a linearmore » relationship, which is not always the case. The second tracks changes in the frequency content of the signal. The third algorithm tracks changes in the temporal moments of a signal over a full test. This method does not require that the changes in the signal be represented by a linear relationship, but attaching changes in the temporal moments to physical events can be difficult. This study describes the algorithm paths applied to experimental data from ultrasonic signals as wax melts and explores different ways to display the results.« less

Carbon nanoparticles induce ceramide- and lipid raft-dependent signalling in lung epithelial cells: a target for a preventive strategy against environmentally-induced lung inflammation

PubMed Central

2012-01-01

Background Particulate air pollution in lung epithelial cells induces pathogenic endpoints like proliferation, apoptosis, and pro-inflammatory reactions. The activation of the epidermal growth factor receptor (EGFR) is a key event responsible for signalling events involving mitogen activated protein kinases specific for these endpoints. The molecular events leading to receptor activation however are not well understood. These events are relevant for the toxicological evaluation of inhalable particles as well as for potential preventive strategies in situations when particulate air pollution cannot be avoided. The current study therefore had the objective to elucidate membrane-coupled events leading to EGFR activation and the subsequent signalling cascade in lung epithelial cells. Furthermore, we aimed to identify the molecular target of ectoine, a biophysical active substance which we described to prevent carbon nanoparticle-induced lung inflammation. Methods Membrane signalling events were investigated in isolated lipid rafts from lung epithelial cells with regard to lipid and protein content of the signalling platforms. Using positive and negative intervention approaches, lipid raft changes, subsequent signalling events, and lung inflammation were investigated in vitro in lung epithelial cells (RLE-6TN) and in vivo in exposed animals. Results Carbon nanoparticle treatment specifically led to an accumulation of ceramides in lipid rafts. Detailed analyses demonstrated a causal link of ceramides and subsequent EGFR activation coupled with a loss of the receptor in the lipid raft fractions. In vitro and in vivo investigations demonstrate the relevance of these events for carbon nanoparticle-induced lung inflammation. Moreover, the compatible solute ectoine was able to prevent ceramide-mediated EGFR phosphorylation and subsequent signalling as well as lung inflammation in vivo. Conclusion The data identify a so far unknown event in pro-inflammatory signalling and contribute to the understanding of particle cell interaction and therefore to risk identification and risk assessment of inhalable xenobiotics. Moreover, as this cellular reaction can be prevented by the well tolerated substance ectoine, a molecular preventive strategy for susceptible persons against airway inflammation is proposed. PMID:23228165

Detection and characterization of debris avalanche and pyroclastic flow dynamics from the simulation of the seismic signal they generate: application to Montserrat, Lesser Antilles

NASA Astrophysics Data System (ADS)

Zhao, J.; Mangeney, A.; Moretti, L.; Stutzmann, E.; Calder, E. S.; Smith, P. J.; Capdeville, Y.; Le Friant, A.; Cole, P.; Luckett, R.; Robertson, R.

2011-12-01

Gravitational instabilities such as debris avalanches or pyroclastic flows represent one of the major natural hazards for populations who live in mountainous or volcanic areas. Detection and understanding of the dynamics of these events is crucial for risk assessment. Furthermore, during an eruption, a series of explosions and gravitational flows can occur, making it difficult to retrieve the characteristics of the individual gravitational events such as their volume, velocity, etc. In this context, the seismic signal generated by these events provides a unique tool to extract information on the history of the eruptive process and to validate gravitational flow models. We analyze here a series of events including explosions, debris avalanche and pyroclastic flows occurring in Montserrat in December 1997. This seismic signal is composed of six main pulses. The characteristics of the seismic signals generated by pyroclastic flows (amplitude, emergent onset, frequency spectrum, etc.) are described and linked to the volume of the individual events estimated from past field surveys. As a first step, we simulate the waveform of each event by assuming that the generation process reduces to a simple force applied at the surface of the topography. Going further, we perform detailed numerical simulation of the Boxing Day debris avalanche and of the following pyroclastic flow using a landslide model able to take into account the 3D topography. The stress field generated by the gravitational flows on the topography is then applied as surface boundary condition in a wave propagation model, making it possible to simulate the seismic signal generated by the avalanche and pyroclastic flow. Comparison between the simulated signal and the seismic signal recorded at the Puerto Rico seismic station located 450 km away from the source, show that this method allows us to reproduce the low frequency seismic signal and to constrain the volume and frictional behavior of the individual events. As a result, simulation of seismic signals generated by gravitational flows provides insight into the history of eruptive sequences and into the characteristics of the individual events.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osovizky, A.; Rotem Industries Ltd, Rotem Industrial Park; University of Maryland, College park, Maryland

A Chromatic Analysis Neutron Diffractometer Or Reflectometer (CANDOR) is under development at the NIST Center for Neutron Research (NCNR). The CANDOR neutron sensor will rely on scintillator material for detecting the neutrons scattered by the sample under test. It consists of {sup 6}LiF:ZnS(Ag) scintillator material into which wavelength shifting (WLS) fibers have been embedded. Solid state photo-sensors (silicon photomultipliers) coupled to the WLS fibers are used to detect the light produced by the neutron capture event ({sup 6}Li (n,α) {sup 3}H reaction) and ionization of the ZnS(Ag). This detector configuration has the potential to accomplish the CANDOR performance requirements formore » efficiency of 90% for 5 A (3.35 meV) neutrons with high gamma rejection (10{sup 7}) along with compact design, affordable cost and materials availability. However this novel design includes challenges for precise neutron detection. The recognizing of the neutron signature versus the noise event produce by gamma event cannot be easy overcome by pulse height discrimination obstacle as can be achieved with {sup 3}He gas tube. Furthermore the selection of silicon photomultipliers (SiPM) as the light sensor maintains the obstacle of dark noise that does not exist when a photomultiplier tube is coupled to the scintillator. A proper selection of SiPM should focus on increasing the output signal and reducing the dark noise in order to optimize the detection sensitivity and to provide a clean signal pulse shape discrimination. The main parameters for evaluation are: - Quantum Efficiency (QE) - matching the SiPM peak QE with the peak transmission wavelength emission of the WLS. - Recovery time - a short recovery time is preferred to minimize the pulse width beyond the intrinsic decay time of the scintillator crystal (improves the gamma rejection based output pulse shape (time)). - Diode dimensions -The dark noise is proportional to the diode active area while the signal is provided by the WLS fibers; therefore the diode area should ideally be only minimally larger than fiber bundle area. - Low dark noise - it is desirable to minimize the dark noise during the pulse integration period so as to minimize the background for pulse shape discrimination. - Photon Detection Efficiency - it is desirable to increase the SiPM PDE in order to enhance light collection. This will increase the likelihood of detecting neutron events with lower light production and will present a cleaner raw signal for pulse shape discrimination. We will present the SiPM optimization process and studies of dark noise and gamma and neutron sensitivity as a function of bias voltage and operating temperature that have enabled us to optimize the detector sensitivity and gamma rejection. The gamma rejection performance goal requires to overcome the challenge of discriminating between the light signature accepted by neutron event to the one received by the noise. In addition there is a huge variation between the number of light photons that reaching the WLS fibers for different neutron events caused by the heavy ions energy losses prior to ionizing the ZnS(Ag) and the high light attenuation of the scintillation mixture. This variation in the light signal along with the long decay time of the ZnS(Ag) (tens of microseconds) can cause double counting of the same neutron event in the case of high light output signature or preventing the detection of low sequential light output signature neutron event. We will presents the algorithm developed for {sup 6}LiF:ZnS(Ag) sensor readout and the results achieved by an off-line analysis by Matlab software code that successfully achieved both the high gamma rejection with a sensitive and accurate neutron event detection. (authors)« less

Passive (Micro-) Seismic Event Detection by Identifying Embedded "Event" Anomalies Within Statistically Describable Background Noise

NASA Astrophysics Data System (ADS)

Baziw, Erick; Verbeek, Gerald

2012-12-01

Among engineers there is considerable interest in the real-time identification of "events" within time series data with a low signal to noise ratio. This is especially true for acoustic emission analysis, which is utilized to assess the integrity and safety of many structures and is also applied in the field of passive seismic monitoring (PSM). Here an array of seismic receivers are used to acquire acoustic signals to monitor locations where seismic activity is expected: underground excavations, deep open pits and quarries, reservoirs into which fluids are injected or from which fluids are produced, permeable subsurface formations, or sites of large underground explosions. The most important element of PSM is event detection: the monitoring of seismic acoustic emissions is a continuous, real-time process which typically runs 24 h a day, 7 days a week, and therefore a PSM system with poor event detection can easily acquire terabytes of useless data as it does not identify crucial acoustic events. This paper outlines a new algorithm developed for this application, the so-called SEED™ (Signal Enhancement and Event Detection) algorithm. The SEED™ algorithm uses real-time Bayesian recursive estimation digital filtering techniques for PSM signal enhancement and event detection.

Acute Kidney Injury and Bisphosphonate Use in Cancer: A Report From the Research on Adverse Drug Events and Reports (RADAR) Project

PubMed Central

Edwards, Beatrice J.; Usmani, Sarah; Raisch, Dennis W.; McKoy, June M.; Samaras, Athena T.; Belknap, Steven M.; Trifilio, Steven M.; Hahr, Allison; Bunta, Andrew D.; Abu-Alfa, Ali; Langman, Craig B.; Rosen, Steve T.; West, Dennis P.

2013-01-01

Purpose: To determine whether acute kidney injury (AKI) is identified within the US Food and Drug Administration's Adverse Events and Reporting System (FDA AERS) as an adverse event resulting from bisphosphonate (BP) use in cancer therapy. Methods: A search of the FDA AERS records from January 1998 through June 2009 was performed; search terms were “renal problems” and all drug names for BPs. The search resulted in 2,091 reports. We analyzed for signals of disproportional association by calculating the proportional reporting ratio for zoledronic acid (ZOL) and pamidronate. Literature review of BP-associated renal injury within the cancer setting was conducted. Results: Four hundred eighty cases of BP-associated acute kidney injury (AKI) were identified in patients with cancer. Two hundred ninety-eight patients (56%) were female; mean age was 66 ± 10 years. Multiple myeloma (n = 220, 46%), breast cancer (n = 98, 20%), and prostate cancer (n = 24, 5%) were identified. Agents included ZOL (n = 411, 87.5%), pamidronate (n = 8, 17%), and alendronate (n = 36, 2%). Outcomes included hospitalization (n = 304, 63.3%) and death (n = 68, 14%). The proportional reporting ratio for ZOL was 1.22 (95% CI, 1.13 to 1.32) and for pamidronate was 1.55 (95% CI, 1.25 to 1.65), reflecting a nonsignificant safety signal for both drugs. Conclusion: AKI was identified in BP cancer clinical trials, although a safety signal for BPs and AKI within the FDA AERS was not detected. Our findings may be attributed, in part, to clinicians who believe that AKI occurs infrequently; ascribe the AKI to underlying premorbid disease, therapy, or cancer progression; or consider that AKI is a known adverse drug reaction of BPs and thus under-report AKI to the AERS. PMID:23814519

Differential diagnosis of apneas in preterm infants.

PubMed

Paul, Karel; Melichar, Jan; Miletín, Jan; Dittrichová, Jaroslava

2009-02-01

Clinically relevant apneas, which are common in preterm infants, may adversely affect later neuropsychological condition in this group of patients. Pharmacotherapy to stimulate respiratory functions may be unsuccessful. Polygraphic recording may help in the differential diagnosis of these clinically relevant events. Twenty-nine preterm neonates born before 36 weeks of gestational age were examined using polygraphic recording (respiration--two channels, perioral electromyography, oxygen saturation, heart rate, electroencephalography, electrocardiography, electrooculography). The examination was ordered by the attending physician after an unsuccessful treatment of apnea by Aminophylline, and it should contribute to the clarification of the causes of these events. In the course of the polygraphic examinations, altogether 63 episodes were recorded during which the pulse oximeter alarm signal was set off. In 42 cases, the alarm signal was set off in events during which SaO(2) fell below 85%. In the remaining 21 cases, the alarm signal was set off in episodes during which early bradycardia below 90/min occurred. The onset of apnea was very often associated with the phasic increase of the perioral electromyography and with electroencephalography arousal reaction. Because of suspicion that these apneas may be triggered by episodes of gastroesophageal reflux, the interruption of the Aminophylline treatment and setting up an antireflux regimen were recommended. These therapeutic measures had a positive effect: The frequency of alarm signals decreased within 48 h by a statistically significant 50%. In cases where the pharmacotherapy of apnea by stimulation of respiratory functions is not successful, differential diagnostic analysis should be performed. Polygraphy may contribute to the clarification of the causes underlying clinically relevant apneas in a view of newly described polygraphic signs. It is feasible to suspect, based on these signs, that gastroesophageal reflux is the cause for clinically significant apneas in that case.

Optimal weighted averaging of event related activity from acquisitions with artifacts.

PubMed

Vollero, Luca; Petrichella, Sara; Innello, Giulio

2016-08-01

In several biomedical applications that require the signal processing of biological data, the starting procedure for noise reduction is the ensemble averaging of multiple repeated acquisitions (trials). This method is based on the assumption that each trial is composed of two additive components: (i) a time-locked activity related to some sensitive/stimulation phenomenon (ERA, Event Related Activity in the following) and (ii) a sum of several other non time-locked background activities. The averaging aims at estimating the ERA activity under very low Signal to Noise and Interference Ratio (SNIR). Although averaging is a well established tool, its performance can be improved in the presence of high-power disturbances (artifacts) by a trials classification and removal stage. In this paper we propose, model and evaluate a new approach that avoids trials removal, managing trials classified as artifact-free and artifact-prone with two different weights. Based on the model, a weights tuning is possible and through modeling and simulations we show that, when optimally configured, the proposed solution outperforms classical approaches.

A role for the tyrosine kinase ACK1 in neurotrophin signaling and neuronal extension and branching

PubMed Central

La Torre, A; del Mar Masdeu, M; Cotrufo, T; Moubarak, R S; del Río, J A; Comella, J X; Soriano, E; Ureña, J M

2013-01-01

Neurotrophins are involved in many crucial cellular functions, including neurite outgrowth, synapse formation, and plasticity. Although these events have long been known, the molecular determinants underlying neuritogenesis have not been fully characterized. Ack1 (activated Cdc42-associated tyrosine kinase) is a non-receptor tyrosine kinase that is highly expressed in the brain. Here, we demonstrate that Ack1 is a molecular constituent of neurotrophin signaling cascades in neurons and PC12 cells. We report that Ack1 interacts with Trk receptors and becomes tyrosine phosphorylated and its kinase activity is increased in response to neurotrophins. Moreover, our data indicate that Ack1 acts upstream of the Akt and MAPK pathways. We show that Ack1 overexpression induces neuritic outgrowth and promotes branching in neurotrophin-treated neuronal cells, whereas the expression of Ack1 dominant negatives or short-hairpin RNAs counteract neurotrophin-stimulated differentiation. Our results identify Ack1 as a novel regulator of neurotrophin-mediated events in primary neurons and in PC12 cells. PMID:23598414

Anchored phosphatases modulate glucose homeostasis

PubMed Central

Hinke, Simon A; Navedo, Manuel F; Ulman, Allison; Whiting, Jennifer L; Nygren, Patrick J; Tian, Geng; Jimenez-Caliani, Antonio J; Langeberg, Lorene K; Cirulli, Vincenzo; Tengholm, Anders; Dell'Acqua, Mark L; Santana, L Fernando; Scott, John D

2012-01-01

Endocrine release of insulin principally controls glucose homeostasis. Nutrient-induced exocytosis of insulin granules from pancreatic β-cells involves ion channels and mobilization of Ca2+ and cyclic AMP (cAMP) signalling pathways. Whole-animal physiology, islet studies and live-β-cell imaging approaches reveal that ablation of the kinase/phosphatase anchoring protein AKAP150 impairs insulin secretion in mice. Loss of AKAP150 impacts L-type Ca2+ currents, and attenuates cytoplasmic accumulation of Ca2+ and cAMP in β-cells. Yet surprisingly AKAP150 null animals display improved glucose handling and heightened insulin sensitivity in skeletal muscle. More refined analyses of AKAP150 knock-in mice unable to anchor protein kinase A or protein phosphatase 2B uncover an unexpected observation that tethering of phosphatases to a seven-residue sequence of the anchoring protein is the predominant molecular event underlying these metabolic phenotypes. Thus anchored signalling events that facilitate insulin secretion and glucose homeostasis may be set by AKAP150 associated phosphatase activity. PMID:22940692

Development of minimum standards for event-based data collection loggers and performance measure definitions for signalized intersections.

DOT National Transportation Integrated Search

2017-01-01

The arterial traffic signal performance measures were not used to their fullest potential in the past. The development of traffic signal controllers with event-based, high-resolution data logging capabilities enabled the advances in derivation and vi...

Electrostatic precursors to granular slip events

PubMed Central

Shinbrot, Troy; Kim, Nam H.; Thyagu, N. Nirmal

2012-01-01

It has been known for over a century that electrical signals are produced by material failure, for example during crack formation of crystals and glasses, or stick-slip motion of liquid mercury on glass. We describe here new experiments revealing that slip events in cohesive powders also produce electrical signals, and remarkably these signals can appear significantly in advance of slip events. We have confirmed this effect in two different experimental systems and using two common powdered materials, and in a third experiment we have demonstrated that similar voltage signals are produced by crack-like defects in several powdered materials. PMID:22689956

Performance Evaluation Modeling of Network Sensors

NASA Technical Reports Server (NTRS)

Clare, Loren P.; Jennings, Esther H.; Gao, Jay L.

2003-01-01

Substantial benefits are promised by operating many spatially separated sensors collectively. Such systems are envisioned to consist of sensor nodes that are connected by a communications network. A simulation tool is being developed to evaluate the performance of networked sensor systems, incorporating such metrics as target detection probabilities, false alarms rates, and classification confusion probabilities. The tool will be used to determine configuration impacts associated with such aspects as spatial laydown, and mixture of different types of sensors (acoustic, seismic, imaging, magnetic, RF, etc.), and fusion architecture. The QualNet discrete-event simulation environment serves as the underlying basis for model development and execution. This platform is recognized for its capabilities in efficiently simulating networking among mobile entities that communicate via wireless media. We are extending QualNet's communications modeling constructs to capture the sensing aspects of multi-target sensing (analogous to multiple access communications), unimodal multi-sensing (broadcast), and multi-modal sensing (multiple channels and correlated transmissions). Methods are also being developed for modeling the sensor signal sources (transmitters), signal propagation through the media, and sensors (receivers) that are consistent with the discrete event paradigm needed for performance determination of sensor network systems. This work is supported under the Microsensors Technical Area of the Army Research Laboratory (ARL) Advanced Sensors Collaborative Technology Alliance.

A Decentralized Event-Triggered Dissipative Control Scheme for Systems With Multiple Sensors to Sample the System Outputs.

PubMed

Zhang, Xian-Ming; Han, Qing-Long

2016-12-01

This paper is concerned with decentralized event-triggered dissipative control for systems with the entries of the system outputs having different physical properties. Depending on these different physical properties, the entries of the system outputs are grouped into multiple nodes. A number of sensors are used to sample the signals from different nodes. A decentralized event-triggering scheme is introduced to select those necessary sampled-data packets to be transmitted so that communication resources can be saved significantly while preserving the prescribed closed-loop performance. First, in order to organize the decentralized data packets transmitted from the sensor nodes, a data packet processor (DPP) is used to generate a new signal to be held by the zero-order-hold once the signal stored by the DPP is updated at some time instant. Second, under the mechanism of the DPP, the resulting closed-loop system is modeled as a linear system with an interval time-varying delay. A sufficient condition is derived such that the closed-loop system is asymptotically stable and strictly (Q 0 ,S 0 ,R 0 ) -dissipative, where Q 0 ,S 0 , and R 0 are real matrices of appropriate dimensions with Q 0 and R 0 symmetric. Third, suitable output-based controllers can be designed based on solutions to a set of a linear matrix inequality. Finally, two examples are given to demonstrate the effectiveness of the proposed method.

Attenuation of harmonic noise in vibroseis data using Simulated Annealing

NASA Astrophysics Data System (ADS)

Sharma, S. P.; Tildy, Peter; Iranpour, Kambiz; Scholtz, Peter

2009-04-01

Processing of high productivity vibroseis seismic data (such as slip-sweep acquisition records) suffers from the well known disadvantage of harmonic distortion. Harmonic distortions are observed after cross-correlation of the recorded seismic signal with the pilot sweep and affect the signals in negative time (before the actual strong reflection event). Weak reflection events of the earlier sweeps falling in the negative time window of the cross-correlation sequence are being masked by harmonic distortions. Though the amplitude of the harmonic distortion is small (up to 10-20 %) compared to the fundamental amplitude of the reflection events, but it is significant enough to mask weak reflected signals. Elimination of harmonic noise due to source signal distortion from the cross-correlated seismic trace is a challenging task since the application of vibratory sources started and it still needs improvement. An approach has been worked out that minimizes the level of harmonic distortion by designing the signal similar to the harmonic distortion. An arbitrary length filter is optimized using the Simulated Annealing global optimization approach to design a harmonic signal. The approach deals with the convolution of a ratio trace (ratio of the harmonics with respect to the fundamental sweep) with the correlated "positive time" recorded signal and an arbitrary filter. Synthetic data study has revealed that this procedure of designing a signal similar to the desired harmonics using convolution of a suitable filter with theoretical ratio of harmonics with fundamental sweep helps in reducing the problem of harmonic distortion. Once we generate a similar signal for a vibroseis source using an optimized filter, then, this filter could be used to generate harmonics, which can be subtracted from the main cross-correlated trace to get the better, undistorted image of the subsurface. Designing the predicted harmonics to reduce the energy in the trace by considering weak reflection and observed harmonics together yields the desired result (resolution of weak reflected signal from the harmonic distortion). As optimization steps proceeds forward it is possible to observe from the difference plots of desired and predicted harmonics how weak reflections evolved from the harmonic distortion gradually during later iterations of global optimization. The procedure is applied in resolving weak reflections from a number of traces considered together. For a more precise design of harmonics SA procedure needs longer computation time which is impractical to deal with voluminous seismic data. However, the objective of resolving weak reflection signal in the strong harmonic noise can be achieved with fast computation using faster cooling schedule and less number of iterations and number of moves in simulated annealing procedure. This process could help in reducing the harmonics distortion and achieving the objective of resolving the lost weak reflection events in the cross-correlated seismic traces. Acknowledgements: The research was supported under the European Marie Curie Host Fellowships for Transfer of Knowledge (TOK) Development Host Scheme (contract no. MTKD-CT-2006-042537).

Tsunami magnetic signals in the Northwestern Pacific seafloor magnetic measurements

NASA Astrophysics Data System (ADS)

Schnepf, N. R.; An, C.; Nair, M. C.; Maus, S.

2013-12-01

In the past two decades, underwater cables and seafloor magnetometers have observed motional inductance from ocean tsunamis. This study aimed to characterize the electromagnetic signatures of tsunamis from seafloor stations to assist in the long-term goal of real-time tsunami detection and warning systems. Four ocean seafloor stations (T13, T14, T15, T18) in the Northeastern Philippine Sea collected vector measurements of the electric and magnetic fields every minute during the period of 10/05/2005 to 11/30/2007 (Baba et al., 2010 PEPI). During this time, four major tsunamis occurred as a result of moment magnitude 8.0-8.1 earthquakes. These tsunamis include the 05/03/2006 Tonga event, the 01/13/2007 Kuril Islands event, the 04/01/2007 Solomon Islands event, and the 08/15/2007 Peru event. The Cornell Multi-grid Coupled Tsunami model (COMCOT) was used to predict the arrival time of the tsunamis at each of the seafloor stations. The stations' raw magnetic field signals underwent a high pass filter to then be examined for signals of the tsunami arrival. The high pass filtering showed clear tsunami signals for the Tonga event, but a clear signal was not seen for the other events. This may be due to signals from near Earth space with periods similar to tsunamis. To remove extraneous atmospheric magnetic signals, a cross-wavelet analysis was conducted using the horizontal field components from three INTERMAGNET land stations and the vertical component from the seafloor stations. The cross-wavelet analysis showed that for three of the six stations (two of the four tsunami events) the peak in wavelet amplitude matched the arrival of the tsunami. We discuss implications of our finding in magnetic monitoring of tsunamis.

Infrasound and seismic analysis of the SpaceX Falcon9 explosion sequence of 1-September-2016

NASA Astrophysics Data System (ADS)

Thompson, G.; McNutt, S. R.; Brown, R. G.; Braunmiller, J.; Mehta, C.

2017-12-01

During a static launch test on 1-Sep-2016 at Kennedy Space Center, a SpaceX Falcon 9 rocket exploded causing loss of the rocket and the payload, and extensively damaging the launch complex. The sequence was captured by a 3-element infrasound array and a broadband 3-component seismometer at the Astronaut Beach House, just 0.87 miles (1.4 km) from the launch pad. Manual picking identified 153 impulsive airwave signals over a 26-minute interval and these were compared to video recordings of the sequence. The explosion onset consisted of a moderate signal on both seismic and infrasound (52 Pa) instruments. This corresponds to the rupture of the second-stage fuel tank. We found no signals before this, so we do not believe that there was an external cause. The primary fuel tank ruptured 4 seconds later and was the strongest event by far, producing an infrasound signal that exceeded 1400 Pa ( 2000 Pa in reduced pressure). The seismic signal consists mainly of air-coupled Rayleigh waves with frequencies of 5-23 Hz. The infrasound events occurred in four clusters. The first cluster included the onset and main events and 46 smaller events. This was followed by several minutes without infrasound signals during which a 3.5 minute continuous seismic vibration occurred. Cluster 2 consisted of 4 events ranging from 117-256 Pa. Cluster 3 comprised 96 events of 7-78 Pa. Cluster 4 consisted of 5 events with overpressures of 23-63 Pa. Gaps of several minutes without infrasound and seismic signals occurred between clusters 2 and 3, and 3 and 4. In terms of energy, the main event dominated; in terms of numbers, cluster 3 had the most infrasound events. The seismic and infrasound data are complementary to video recordings of the explosion, and provide additional characterization that may be useful to interpret the sequence of events. Because of the proximity of our array to this rocket explosion, our dataset may be unique.

COMPTEL solar flare observations

NASA Technical Reports Server (NTRS)

Ryan, J. M.; Aarts, H.; Bennett, K.; Debrunner, H.; Devries, C.; Denherder, J. W.; Eymann, G.; Forrest, D. J.; Diehl, R.; Hermsen, W.

1992-01-01

COMPTEL as part of a solar target of opportunity campaign observed the sun during the period of high solar activity from 7-15 Jun. 1991. Major flares were observed on 9 and 11 Jun. Although both flares were large GOES events (greater than or = X10), they were not extraordinary in terms of gamma-ray emission. Only the decay phase of the 15 Jun. flare was observed by COMPTEL. We report the preliminary analysis of data from these flares, including the first spectroscopic measurement of solar flare neutrons. The deuterium formation line at 2.223 MeV was present in both events and for at least the 9 Jun. event, was comparable to the flux in the nuclear line region of 4-8 MeV, consistent with Solar-Maximum Mission (SSM) Observations. A clear neutron signal was present in the flare of 9 Jun. with the spectrum extending up to 80 MeV and consistent in time with the emission of gamma-rays, confirming the utility of COMPTEL in measuring the solar neutron flux at low energies. The neutron flux below 100 MeV appears to be lower than that of the 3 Jun. 1982 flare by more than an order of magnitude. The neutron signal of the 11 Jun. event is under study. Severe dead time effects resulting from the intense thermal x-rays require significant corrections to the measured flux which increase the magnitude of the associated systematic uncertainties.

Acoustic emission-based sensor analysis and damage classification for structural health monitoring of composite structures

NASA Astrophysics Data System (ADS)

Uprety, Bibhisha

Within the aerospace industry the need to detect and locate impact events, even when no visible damage is present, is important both from the maintenance and design perspectives. This research focused on the use of Acoustic Emission (AE) based sensing technologies to identify impact events and characterize damage modes in composite structures for structural health monitoring. Six commercially available piezoelectric AE sensors were evaluated for use with impact location estimation algorithms under development at the University of Utah. Both active and passive testing were performed to estimate the time of arrival and plate wave mode velocities for impact location estimation. Four sensors were recommended for further comparative investigations. Furthermore, instrumented low-velocity impact experiments were conducted on quasi-isotropic carbon/epoxy composite laminates to initiate specific types of damage: matrix cracking, delamination and fiber breakage. AE signal responses were collected during impacting and the test panels were ultrasonically C-scanned after impact to identify the internal damage corresponding to the AE signals. Matrix cracking and delamination damage produced using more compliant test panels and larger diameter impactor were characterized by lower frequency signals while fiber breakage produced higher frequency responses. The results obtained suggest that selected characteristics of sensor response signals can be used both to determine whether damage is produced during impacting and to characterize the types of damage produced in an impacted composite structure.

Welding quality evaluation of resistance spot welding using the time-varying inductive reactance signal

NASA Astrophysics Data System (ADS)

Zhang, Hongjie; Hou, Yanyan; Yang, Tao; Zhang, Qian; Zhao, Jian

2018-05-01

In the spot welding process, a high alternating current is applied, resulting in a time-varying electromagnetic field surrounding the welder. When measuring the welding voltage signal, the impedance of the measuring circuit consists of two parts: dynamic resistance relating to weld nugget nucleation event and inductive reactance caused by mutual inductance. The aim of this study is to develop a method to acquire the dynamic reactance signal and to discuss the possibility of using this signal to evaluate the weld quality. For this purpose, a series of experiments were carried out. The reactance signals under different welding conditions were compared and the results showed that the morphological feature of the reactance signal was closely related to the welding current and it was also significantly influenced by some abnormal welding conditions. Some features were extracted from the reactance signal and combined to construct weld nugget strength and diameter prediction models based on the radial basis function (RBF) neural network. In addition, several features were also used to monitor the expulsion in the welding process by using Fisher linear discriminant analysis. The results indicated that using the dynamic reactance signal to evaluate weld quality is possible and feasible.

Data-Enabled Quantification of Aluminum Microstructural Damage Under Tensile Loading

NASA Astrophysics Data System (ADS)

Wayne, Steven F.; Qi, G.; Zhang, L.

2016-08-01

The study of material failure with digital analytics is in its infancy and offers a new perspective to advance our understanding of damage initiation and evolution in metals. In this article, we study the failure of aluminum using data-enabled methods, statistics and data mining. Through the use of tension tests, we establish a multivariate acoustic-data matrix of random damage events, which typically are not visible and are very difficult to measure due to their variability, diversity and interactivity during damage processes. Aluminium alloy 6061-T651 and single crystal aluminium with a (111) orientation were evaluated by comparing the collection of acoustic signals from damage events caused primarily by slip in the single crystal and multimode fracture of the alloy. We found the resulting acoustic damage-event data to be large semi-structured volumes of Big Data with the potential to be mined for information that describes the materials damage state under strain. Our data-enabled analyses has allowed us to determine statistical distributions of multiscale random damage that provide a means to quantify the material damage state.

Global quantitative analysis of phosphorylation underlying phencyclidine signaling and sensorimotor gating in the prefrontal cortex.

PubMed

McClatchy, D B; Savas, J N; Martínez-Bartolomé, S; Park, S K; Maher, P; Powell, S B; Yates, J R

2016-02-01

Prepulse inhibition (PPI) is an example of sensorimotor gating and deficits in PPI have been demonstrated in schizophrenia patients. Phencyclidine (PCP) suppression of PPI in animals has been studied to elucidate the pathological elements of schizophrenia. However, the molecular mechanisms underlying PCP treatment or PPI in the brain are still poorly understood. In this study, quantitative phosphoproteomic analysis was performed on the prefrontal cortex from rats that were subjected to PPI after being systemically injected with PCP or saline. PCP downregulated phosphorylation events were significantly enriched in proteins associated with long-term potentiation (LTP). Importantly, this data set identifies functionally novel phosphorylation sites on known LTP-associated signaling molecules. In addition, mutagenesis of a significantly altered phosphorylation site on xCT (SLC7A11), the light chain of system xc-, the cystine/glutamate antiporter, suggests that PCP also regulates the activity of this protein. Finally, new insights were also derived on PPI signaling independent of PCP treatment. This is the first quantitative phosphorylation proteomic analysis providing new molecular insights into sensorimotor gating.

Megathrust Earthquake Swarms Contemporaneous to Slow Slip and Non-Volcanic Tremor in Southern Mexico, Detected and Analyzed through a Template Matching Approach

NASA Astrophysics Data System (ADS)

Holtkamp, S.; Brudzinski, M. R.; Cabral-Cano, E.; Arciniega-Ceballos, A.

2012-12-01

An outstanding question in geophysics is the degree to which the newly discovered types of slow fault slip are related to their destructive cousin - the earthquake. Here, we utilize a local network along the Oaxacan segment of the Middle American subduction zone to investigate the potential relationship between slow slip, non-volcanic tremor (NVT), and earthquakes along the subduction megathrust. We have developed a multi-station "template matching" waveform cross correlation technique which is able to detect and locate events several orders of magnitude smaller than would be possible using more traditional techniques. Also, our template matching procedure is capable of consistently locate events which occur during periods of increased background activity (e.g., during productive NVT, loud cultural noise, or after larger earthquakes) because the multi-station detector is finely tuned to events with similar hypocentral location and focal mechanism. The local network in the Oaxaca region allows us to focus on documented megathrust earthquake swarms, which we focus on because slow slip is hypothesized to be the cause for earthquake swarms in some tectonic environments. We identify a productive earthquake swarm in July 2006 (~600 similar earthquakes detected), which occurred during a week-long episode of productive tremor and slow slip. Families of events in this sequence were also active during larger and longer slow slip events, which provides a potential link between slow slip in the transition zone and earthquakes at the downdip end of the seismogenic portion of the megathrust. Because template matching techniques only detect similar signals, detected waveforms can be stacked together to produce higher signal to noise ratios or cross correlated against each other to produce precise relative phase arrival times. We are using the refined signals to look for evidence of expansion or propagation of hypocenters during these earthquake swarms, which could be used as a test for determining their underlying processes (e.g., fluid diffusion or slow slip).

Possible associated signal with GW150914 in the LIGO data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Hao; Jackson, Andrew D., E-mail: liuhao@nbi.dk, E-mail: jackson@nbi.ku.dk

2016-10-01

We present a simple method for the identification of weak signals associated with gravitational wave events. Its application reveals a signal with the same time lag as the GW150914 event in the released LIGO strain data with a significance of approximately 3.2σ. This signal starts about 10 minutes before GW150914 and lasts for about 45 minutes. Subsequent tests suggest that this signal is likely to be due to external sources.

The modulating effect of personality traits on neural error monitoring: evidence from event-related FMRI.

PubMed

Sosic-Vasic, Zrinka; Ulrich, Martin; Ruchsow, Martin; Vasic, Nenad; Grön, Georg

2012-01-01

The present study investigated the association between traits of the Five Factor Model of Personality (Neuroticism, Extraversion, Openness for Experiences, Agreeableness, and Conscientiousness) and neural correlates of error monitoring obtained from a combined Eriksen-Flanker-Go/NoGo task during event-related functional magnetic resonance imaging in 27 healthy subjects. Individual expressions of personality traits were measured using the NEO-PI-R questionnaire. Conscientiousness correlated positively with error signaling in the left inferior frontal gyrus and adjacent anterior insula (IFG/aI). A second strong positive correlation was observed in the anterior cingulate gyrus (ACC). Neuroticism was negatively correlated with error signaling in the inferior frontal cortex possibly reflecting the negative inter-correlation between both scales observed on the behavioral level. Under present statistical thresholds no significant results were obtained for remaining scales. Aligning the personality trait of Conscientiousness with task accomplishment striving behavior the correlation in the left IFG/aI possibly reflects an inter-individually different involvement whenever task-set related memory representations are violated by the occurrence of errors. The strong correlations in the ACC may indicate that more conscientious subjects were stronger affected by these violations of a given task-set expressed by individually different, negatively valenced signals conveyed by the ACC upon occurrence of an error. Present results illustrate that for predicting individual responses to errors underlying personality traits should be taken into account and also lend external validity to the personality trait approach suggesting that personality constructs do reflect more than mere descriptive taxonomies.

Changes in Intense Precipitation Events in West Africa and the central U.S. under Global Warming

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cook, Kerry H.; Vizy, Edward

The purpose of the proposed project is to improve our understanding of the physical processes and large-scale connectivity of changes in intense precipitation events (high rainfall rates) under global warming in West Africa and the central U.S., including relationships with low-frequency modes of variability. This is in response to the requested subject area #2 “simulation of climate extremes under a changing climate … to better quantify the frequency, duration, and intensity of extreme events under climate change and elucidate the role of low frequency climate variability in modulating extremes.” We will use a regional climate model and emphasize an understandingmore » of the physical processes that lead to an intensification of rainfall. The project objectives are as follows: 1. Understand the processes responsible for simulated changes in warm-season rainfall intensity and frequency over West Africa and the Central U.S. associated with greenhouse gas-induced global warming 2. Understand the relationship between changes in warm-season rainfall intensity and frequency, which generally occur on regional space scales, and the larger-scale global warming signal by considering modifications of low-frequency modes of variability. 3. Relate changes simulated on regional space scales to global-scale theories of how and why atmospheric moisture levels and rainfall should change as climate warms.« less

Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.

PubMed

Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi

2011-01-01

Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association. After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.

Determining dark matter properties with a XENONnT/LZ signal and LHC Run 3 monojet searches

NASA Astrophysics Data System (ADS)

Baum, Sebastian; Catena, Riccardo; Conrad, Jan; Freese, Katherine; Krauss, Martin B.

2018-04-01

We develop a method to forecast the outcome of the LHC Run 3 based on the hypothetical detection of O (100 ) signal events at XENONnT. Our method relies on a systematic classification of renormalizable single-mediator models for dark matter-quark interactions and is valid for dark matter candidates of spin less than or equal to one. Applying our method to simulated data, we find that at the end of the LHC Run 3 only two mutually exclusive scenarios would be compatible with the detection of O (100 ) signal events at XENONnT. In the first scenario, the energy distribution of the signal events is featureless, as for canonical spin-independent interactions. In this case, if a monojet signal is detected at the LHC, dark matter must have spin 1 /2 and interact with nucleons through a unique velocity-dependent operator. If a monojet signal is not detected, dark matter interacts with nucleons through canonical spin-independent interactions. In a second scenario, the spectral distribution of the signal events exhibits a bump at nonzero recoil energies. In this second case, a monojet signal can be detected at the LHC Run 3; dark matter must have spin 1 /2 and interact with nucleons through a unique momentum-dependent operator. We therefore conclude that the observation of O (100 ) signal events at XENONnT combined with the detection, or the lack of detection, of a monojet signal at the LHC Run 3 would significantly narrow the range of possible dark matter-nucleon interactions. As we argued above, it can also provide key information on the dark matter particle spin.

Informational approach to the analysis of acoustic signals

NASA Astrophysics Data System (ADS)

Senkevich, Yuriy; Dyuk, Vyacheslav; Mishchenko, Mikhail; Solodchuk, Alexandra

2017-10-01

The example of linguistic processing of acoustic signals of a seismic event would be an information approach to the processing of non-stationary signals. The method for converting an acoustic signal into an information message is described by identifying repetitive self-similar patterns. The definitions of the event selection indicators in the symbolic recording of the acoustic signal are given. The results of processing an acoustic signal by a computer program realizing the processing of linguistic data are shown. Advantages and disadvantages of using software algorithms are indicated.

A signal detection method for temporal variation of adverse effect with vaccine adverse event reporting system data.

PubMed

Cai, Yi; Du, Jingcheng; Huang, Jing; Ellenberg, Susan S; Hennessy, Sean; Tao, Cui; Chen, Yong

2017-07-05

To identify safety signals by manual review of individual report in large surveillance databases is time consuming; such an approach is very unlikely to reveal complex relationships between medications and adverse events. Since the late 1990s, efforts have been made to develop data mining tools to systematically and automatically search for safety signals in surveillance databases. Influenza vaccines present special challenges to safety surveillance because the vaccine changes every year in response to the influenza strains predicted to be prevalent that year. Therefore, it may be expected that reporting rates of adverse events following flu vaccines (number of reports for a specific vaccine-event combination/number of reports for all vaccine-event combinations) may vary substantially across reporting years. Current surveillance methods seldom consider these variations in signal detection, and reports from different years are typically collapsed together to conduct safety analyses. However, merging reports from different years ignores the potential heterogeneity of reporting rates across years and may miss important safety signals. Reports of adverse events between years 1990 to 2013 were extracted from the Vaccine Adverse Event Reporting System (VAERS) database and formatted into a three-dimensional data array with types of vaccine, groups of adverse events and reporting time as the three dimensions. We propose a random effects model to test the heterogeneity of reporting rates for a given vaccine-event combination across reporting years. The proposed method provides a rigorous statistical procedure to detect differences of reporting rates among years. We also introduce a new visualization tool to summarize the result of the proposed method when applied to multiple vaccine-adverse event combinations. We applied the proposed method to detect safety signals of FLU3, an influenza vaccine containing three flu strains, in the VAERS database. We showed that it had high statistical power to detect the variation in reporting rates across years. The identified vaccine-event combinations with significant different reporting rates over years suggested potential safety issues due to changes in vaccines which require further investigation. We developed a statistical model to detect safety signals arising from heterogeneity of reporting rates of a given vaccine-event combinations across reporting years. This method detects variation in reporting rates over years with high power. The temporal trend of reporting rate across years may reveal the impact of vaccine update on occurrence of adverse events and provide evidence for further investigations.

Blind Source Separation of Seismic Events with Independent Component Analysis: CTBT related exercise

NASA Astrophysics Data System (ADS)

Rozhkov, Mikhail; Kitov, Ivan

2015-04-01

Blind Source Separation (BSS) methods used in signal recovery applications are attractive for they use minimal a priori information about the signals they are dealing with. Homomorphic deconvolution and cepstrum estimation are probably the only methods used in certain extent in CTBT applications that can be attributed to the given branch of technology. However Expert Technical Analysis (ETA) conducted in CTBTO to improve the estimated values for the standard signal and event parameters according to the Protocol to the CTBT may face problems which cannot be resolved with certified CTBTO applications and may demand specific techniques not presently used. The problem to be considered within the ETA framework is the unambiguous separation of signals with close arrival times. Here, we examine two scenarios of interest: (1) separation of two almost co-located explosions conducted within fractions of seconds, and (2) extraction of explosion signals merged with wavetrains from strong earthquake. The importance of resolving the problem related to case 1 is connected with the correct explosion yield estimation. Case 2 is a well-known scenario of conducting clandestine nuclear tests. While the first case can be approached somehow with the means of cepstral methods, the second case can hardly be resolved with the conventional methods implemented at the International Data Centre, especially if the signals have close slowness and azimuth. Independent Component Analysis (in its FastICA implementation) implying non-Gaussianity of the underlying processes signal's mixture is a blind source separation method that we apply to resolve the mentioned above problems. We have tested this technique with synthetic waveforms, seismic data from DPRK explosions and mining blasts conducted within East-European platform as well as with signals from strong teleseismic events (Sumatra, April 2012 Mw=8.6, and Tohoku, March 2011 Mw=9.0 earthquakes). The data was recorded by seismic arrays of the International Monitoring System of CTBTO and by small-aperture seismic array Mikhnevo (MHVAR) operated by the Institute of Geosphere Dynamics, Russian Academy of Sciences. Our approach demonstrated a good ability of separation of seismic sources with very close origin times and locations (hundreds of meters), and/or having close arrival times (fractions of seconds), and recovering their waveforms from the mixture. Perspectives and limitations of the method are discussed.

Episodic inputs of atmospheric nitrogen to the Sargasso Sea: Contributions to new production and phytoplankton blooms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michaels, A.F.; Johnson, R.J.; Siegel, D.A.

1993-06-01

This paper compares a recent atmospheric wet deposition record (including all measurable daily rainfall events between October 1988 and June 1991) with concurrent measurements of nitrogen cycling and biomass at the U.S. Joint Global Ocean Flux Study Bermuda Atlantic Time Series Study station. The two data sets, among the most complete synoptic records of atmospheric nitrogen deposition and ocean nitrogen cycling, provide an opportunity to directly assess the importance of nitrogen deposition in the ocean. The results indicate that individual nitrogen wet deposition events are usually small compared to the ambient nitrogen cycle and that only under sustained calm conditionsmore » following large deposition events will nitrogen deposition processes be an important signal for the understanding of ocean biochemistry. 46 refs., 7 figs.« less

Comparison of 16-Channel Laser Photoreceivers for Topographic Mapping

NASA Technical Reports Server (NTRS)

Krainak, Michael A.; Yang, Guangning; Sun, XiaoIi; Lu, Wei; Bai, Xiaogang; Yuan, Ping; McDonald, Paul; Boisvert, Joseph; Woo, Robyn; Wan, Kam;

Classifier for gravitational-wave inspiral signals in nonideal single-detector data

NASA Astrophysics Data System (ADS)

Kapadia, S. J.; Dent, T.; Dal Canton, T.

2017-11-01

We describe a multivariate classifier for candidate events in a templated search for gravitational-wave (GW) inspiral signals from neutron-star-black-hole (NS-BH) binaries, in data from ground-based detectors where sensitivity is limited by non-Gaussian noise transients. The standard signal-to-noise ratio (SNR) and chi-squared test for inspiral searches use only properties of a single matched filter at the time of an event; instead, we propose a classifier using features derived from a bank of inspiral templates around the time of each event, and also from a search using approximate sine-Gaussian templates. The classifier thus extracts additional information from strain data to discriminate inspiral signals from noise transients. We evaluate a random forest classifier on a set of single-detector events obtained from realistic simulated advanced LIGO data, using simulated NS-BH signals added to the data. The new classifier detects a factor of 1.5-2 more signals at low false positive rates as compared to the standard "reweighted SNR" statistic, and does not require the chi-squared test to be computed. Conversely, if only the SNR and chi-squared values of single-detector events are available, random forest classification performs nearly identically to the reweighted SNR.

Pyranometer offsets triggered by ambient meteorology: insights from laboratory and field experiments

NASA Astrophysics Data System (ADS)

Oswald, Sandro M.; Pietsch, Helga; Baumgartner, Dietmar J.; Weihs, Philipp; Rieder, Harald E.

2017-03-01

This study investigates the effects of ambient meteorology on the accuracy of radiation (R) measurements performed with pyranometers contained in various heating and ventilation systems (HV-systems). It focuses particularly on instrument offsets observed following precipitation events. To quantify pyranometer responses to precipitation, a series of controlled laboratory experiments as well as two targeted field campaigns were performed in 2016. The results indicate that precipitation (as simulated by spray tests or observed under ambient conditions) significantly affects the thermal environment of the instruments and thus their stability. Statistical analyses of laboratory experiments showed that precipitation triggers zero offsets of -4 W m-2 or more, independent of the HV-system. Similar offsets were observed in field experiments under ambient environmental conditions, indicating a clear exceedance of BSRN (Baseline Surface Radiation Network) targets following precipitation events. All pyranometers required substantial time to return to their initial signal states after the simulated precipitation events. Therefore, for BSRN-class measurements, the recommendation would be to flag the radiation measurements during a natural precipitation event and 90 min after it in nighttime conditions. Further daytime experiments show pyranometer offsets of 50 W m-2 or more in comparison to the reference system. As they show a substantially faster recovery, the recommendation would be to flag the radiation measurements within a natural precipitation event and 10 min after it in daytime conditions.

Magnetic storms and solar flares: can be analysed within similar mathematical framework with other extreme events?

NASA Astrophysics Data System (ADS)

Balasis, Georgios; Potirakis, Stelios M.; Papadimitriou, Constantinos; Zitis, Pavlos I.; Eftaxias, Konstantinos

2015-04-01

The field of study of complex systems considers that the dynamics of complex systems are founded on universal principles that may be used to describe a great variety of scientific and technological approaches of different types of natural, artificial, and social systems. We apply concepts of the nonextensive statistical physics, on time-series data of observable manifestations of the underlying complex processes ending up to different extreme events, in order to support the suggestion that a dynamical analogy characterizes the generation of a single magnetic storm, solar flare, earthquake (in terms of pre-seismic electromagnetic signals) , epileptic seizure, and economic crisis. The analysis reveals that all the above mentioned different extreme events can be analyzed within similar mathematical framework. More precisely, we show that the populations of magnitudes of fluctuations included in all the above mentioned pulse-like-type time series follow the traditional Gutenberg-Richter law as well as a nonextensive model for earthquake dynamics, with similar nonextensive q-parameter values. Moreover, based on a multidisciplinary statistical analysis we show that the extreme events are characterized by crucial common symptoms, namely: (i) high organization, high compressibility, low complexity, high information content; (ii) strong persistency; and (iii) existence of clear preferred direction of emerged activities. These symptoms clearly discriminate the appearance of the extreme events under study from the corresponding background noise.

SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals.

PubMed

Oosterveen, Tony; Kurdija, Sanja; Ensterö, Mats; Uhde, Christopher W; Bergsland, Maria; Sandberg, Magnus; Sandberg, Rickard; Muhr, Jonas; Ericson, Johan

2013-04-30

The reiterative deployment of a small cadre of morphogen signals underlies patterning and growth of most tissues during embyogenesis, but how such inductive events result in tissue-specific responses remains poorly understood. By characterizing cis-regulatory modules (CRMs) associated with genes regulated by Sonic hedgehog (Shh), retinoids, or bone morphogenetic proteins in the CNS, we provide evidence that the neural-specific interpretation of morphogen signaling reflects a direct integration of these pathways with SoxB1 proteins at the CRM level. Moreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to activate neural-specific target genes upon Shh, retinoid, or bone morphogenetic protein signaling, and the collocation of binding sites for SoxB1 and morphogen-mediatory transcription factors in CRMs faithfully predicts neural-specific gene activity. Thus, an unexpectedly simple transcriptional paradigm appears to conceptually explain the neural-specific interpretation of pleiotropic signaling during vertebrate development. Importantly, genes induced in a SoxB1-dependent manner appear to constitute repressive gene regulatory networks that are directly interlinked at the CRM level to constrain the regional expression of patterning genes. Accordingly, not only does the topology of SoxB1-driven gene regulatory networks provide a tissue-specific mode of gene activation, but it also determines the spatial expression pattern of target genes within the developing neural tube.

Detection of sleep disordered breathing and its central/obstructive character using nasal cannula and finger pulse oximeter.

PubMed

Sommermeyer, Dirk; Zou, Ding; Grote, Ludger; Hedner, Jan

2012-10-15

To assess the accuracy of novel algorithms using an oximeter-based finger plethysmographic signal in combination with a nasal cannula for the detection and differentiation of central and obstructive apneas. The validity of single pulse oximetry to detect respiratory disturbance events was also studied. Patients recruited from four sleep laboratories underwent an ambulatory overnight cardiorespiratory polygraphy recording. The nasal flow and photoplethysmographic signals of the recording were analyzed by automated algorithms. The apnea hypopnea index (AHI(auto)) was calculated using both signals, and a respiratory disturbance index (RDI(auto)) was calculated from photoplethysmography alone. Apnea events were classified into obstructive and central types using the oximeter derived pulse wave signal and compared with manual scoring. Sixty-six subjects (42 males, age 54 ± 14 yrs, body mass index 28.5 ± 5.9 kg/m(2)) were included in the analysis. AHI(manual) (19.4 ± 18.5 events/h) correlated highly significantly with AHI(auto) (19.9 ± 16.5 events/h) and RDI(auto) (20.4 ± 17.2 events/h); the correlation coefficients were r = 0.94 and 0.95, respectively (p < 0.001) with a mean difference of -0.5 ± 6.6 and -1.0 ± 6.1 events/h. The automatic analysis of AHI(auto) and RDI(auto) detected sleep apnea (cutoff AHI(manual) ≥ 15 events/h) with a sensitivity/specificity of 0.90/0.97 and 0.86/0.94, respectively. The automated obstructive/central apnea indices correlated closely with manually scoring (r = 0.87 and 0.95, p < 0.001) with mean difference of -4.3 ± 7.9 and 0.3 ± 1.5 events/h, respectively. Automatic analysis based on routine pulse oximetry alone may be used to detect sleep disordered breathing with accuracy. In addition, the combination of photoplethysmographic signals with a nasal flow signal provides an accurate distinction between obstructive and central apneic events during sleep.

Safety related drug-labelling changes: findings from two data mining algorithms.

PubMed

Hauben, Manfred; Reich, Lester

2004-01-01

With increasing volumes of postmarketing safety surveillance data, data mining algorithms (DMAs) have been developed to search large spontaneous reporting system (SRS) databases for disproportional statistical dependencies between drugs and events. A crucial question is the proper deployment of such techniques within the universe of methods historically used for signal detection. One question of interest is comparative performance of algorithms based on simple forms of disproportionality analysis versus those incorporating Bayesian modelling. A potential benefit of Bayesian methods is a reduced volume of signals, including false-positive signals. To compare performance of two well described DMAs (proportional reporting ratios [PRRs] and an empirical Bayesian algorithm known as multi-item gamma Poisson shrinker [MGPS]) using commonly recommended thresholds on a diverse data set of adverse events that triggered drug labelling changes. PRRs and MGPS were retrospectively applied to a diverse sample of drug-event combinations (DECs) identified on a government Internet site for a 7-month period. Metrics for this comparative analysis included the number and proportion of these DECs that generated signals of disproportionate reporting with PRRs, MGPS, both or neither method, differential timing of signal generation between the two methods, and clinical nature of events that generated signals with only one, both or neither method. There were 136 relevant DECs that triggered safety-related labelling changes for 39 drugs during a 7-month period. PRRs generated a signal of disproportionate reporting with almost twice as many DECs as MGPS (77 vs 40). No DECs were flagged by MGPS only. PRRs highlighted DECs in advance of MGPS (1-15 years) and a label change (1-30 years). For 59 DECs, there was no signal with either DMA. DECs generating signals of disproportionate reporting with only PRRs were both medically serious and non-serious. In most instances in which a DEC generated a signal of disproportionate reporting with both DMAs (almost twice as many with PRRs), the signal was generated using PRRs in advance of MGPS. No medically important events were signalled only by MGPS. It is likely that the incremental utility of DMAs are highly situation-dependent. It is clear, however, that the volume of signals generated by itself is an inadequate criterion for comparison and that clinical nature of signalled events and differential timing of signals needs to be considered. Accepting commonly recommended threshold criteria for DMAs examined in this study as universal benchmarks for signal detection is not justified.

Cellular Homeostasis and Aging.

PubMed

Hartl, F Ulrich

2016-06-02

Aging and longevity are controlled by a multiplicity of molecular and cellular signaling events that interface with environmental factors to maintain cellular homeostasis. Modulation of these pathways to extend life span, including insulin-like signaling and the response to dietary restriction, identified the cellular machineries and networks of protein homeostasis (proteostasis) and stress resistance pathways as critical players in the aging process. A decline of proteostasis capacity during aging leads to dysfunction of specific cell types and tissues, rendering the organism susceptible to a range of chronic diseases. This volume of the Annual Review of Biochemistry contains a set of two reviews addressing our current understanding of the molecular mechanisms underlying aging in model organisms and humans.

Time series data analysis using DFA

NASA Astrophysics Data System (ADS)

Okumoto, A.; Akiyama, T.; Sekino, H.; Sumi, T.

2014-02-01

Detrended fluctuation analysis (DFA) was originally developed for the evaluation of DNA sequence and interval for heart rate variability (HRV), but it is now used to obtain various biological information. In this study we perform DFA on artificially generated data where we already know the relationship between signal and the physical event causing the signal. We generate artificial data using molecular dynamics. The Brownian motion of a polymer under an external force is investigated. In order to generate artificial fluctuation in the physical properties, we introduce obstacle pillars fixed to nanostructures. Using different conditions such as presence or absence of obstacles, external field, and the polymer length, we perform DFA on energies and positions of the polymer.

Signal Detection of Imipenem Compared to Other Drugs from Korea Adverse Event Reporting System Database

PubMed Central

Park, Kyounghoon; Soukavong, Mick; Kim, Jungmee; Kwon, Kyoung-eun; Jin, Xue-mei; Lee, Joongyub; Yang, Bo Ram

2017-01-01

Purpose To detect signals of adverse drug events after imipenem treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD). Materials and Methods We performed data mining using KIDS-KD, which was constructed using spontaneously reported adverse event (AE) reports between December 1988 and June 2014. We detected signals calculated the proportional reporting ratio, reporting odds ratio, and information component of imipenem. We defined a signal as any AE that satisfied all three indices. The signals were compared with drug labels of nine countries. Results There were 807582 spontaneous AEs reports in the KIDS-KD. Among those, the number of antibiotics related AEs was 192510; 3382 reports were associated with imipenem. The most common imipenem-associated AE was the drug eruption; 353 times. We calculated the signal by comparing with all other antibiotics and drugs; 58 and 53 signals satisfied the three methods. We compared the drug labelling information of nine countries, including the USA, the UK, Japan, Italy, Switzerland, Germany, France, Canada, and South Korea, and discovered that the following signals were currently not included in drug labels: hypokalemia, cardiac arrest, cardiac failure, Parkinson's syndrome, myocardial infarction, and prostate enlargement. Hypokalemia was an additional signal compared with all other antibiotics, and the other signals were not different compared with all other antibiotics and all other drugs. Conclusion We detected new signals that were not listed on the drug labels of nine countries. However, further pharmacoepidemiologic research is needed to evaluate the causality of these signals. PMID:28332362

Signal Detection of Imipenem Compared to Other Drugs from Korea Adverse Event Reporting System Database.

PubMed

Park, Kyounghoon; Soukavong, Mick; Kim, Jungmee; Kwon, Kyoung Eun; Jin, Xue Mei; Lee, Joongyub; Yang, Bo Ram; Park, Byung Joo

2017-05-01

To detect signals of adverse drug events after imipenem treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD). We performed data mining using KIDS-KD, which was constructed using spontaneously reported adverse event (AE) reports between December 1988 and June 2014. We detected signals calculated the proportional reporting ratio, reporting odds ratio, and information component of imipenem. We defined a signal as any AE that satisfied all three indices. The signals were compared with drug labels of nine countries. There were 807582 spontaneous AEs reports in the KIDS-KD. Among those, the number of antibiotics related AEs was 192510; 3382 reports were associated with imipenem. The most common imipenem-associated AE was the drug eruption; 353 times. We calculated the signal by comparing with all other antibiotics and drugs; 58 and 53 signals satisfied the three methods. We compared the drug labelling information of nine countries, including the USA, the UK, Japan, Italy, Switzerland, Germany, France, Canada, and South Korea, and discovered that the following signals were currently not included in drug labels: hypokalemia, cardiac arrest, cardiac failure, Parkinson's syndrome, myocardial infarction, and prostate enlargement. Hypokalemia was an additional signal compared with all other antibiotics, and the other signals were not different compared with all other antibiotics and all other drugs. We detected new signals that were not listed on the drug labels of nine countries. However, further pharmacoepidemiologic research is needed to evaluate the causality of these signals. © Copyright: Yonsei University College of Medicine 2017

Slow Earthquakes in the Microseism Frequency Band (0.1-1.0 Hz) off Kii Peninsula, Japan

NASA Astrophysics Data System (ADS)

Kaneko, Lisa; Ide, Satoshi; Nakano, Masaru

2018-03-01

It is difficult to detect the signal of slow deformation in the 0.1-1.0 Hz frequency band between tectonic tremors and very low frequency events, where microseism noise is dominant. Here we provide the first evidence of slow earthquakes in this microseism band, observed by the DONET1 ocean bottom seismometer network, after an Mw 5.8 earthquake off Kii Peninsula, Japan, on 1 April 2016. The signals in the microseism band were accompanied by signals from active tremors, very low frequency events, and slow slip events that radiated from the shallow plate interface. We report the detection and locations of events across five frequency bands, including the microseism band. The locations and timing of the events estimated in the different frequency bands are similar, suggesting that these signals radiated from a common source. The observed variations in detectability for each band highlight the complexity of the slow earthquake process.

Phylogenetic inference under varying proportions of indel-induced alignment gaps

PubMed Central

Dwivedi, Bhakti; Gadagkar, Sudhindra R

2009-01-01

Background The effect of alignment gaps on phylogenetic accuracy has been the subject of numerous studies. In this study, we investigated the relationship between the total number of gapped sites and phylogenetic accuracy, when the gaps were introduced (by means of computer simulation) to reflect indel (insertion/deletion) events during the evolution of DNA sequences. The resulting (true) alignments were subjected to commonly used gap treatment and phylogenetic inference methods. Results (1) In general, there was a strong – almost deterministic – relationship between the amount of gap in the data and the level of phylogenetic accuracy when the alignments were very "gappy", (2) gaps resulting from deletions (as opposed to insertions) contributed more to the inaccuracy of phylogenetic inference, (3) the probabilistic methods (Bayesian, PhyML & "MLε, " a method implemented in DNAML in PHYLIP) performed better at most levels of gap percentage when compared to parsimony (MP) and distance (NJ) methods, with Bayesian analysis being clearly the best, (4) methods that treat gapped sites as missing data yielded less accurate trees when compared to those that attribute phylogenetic signal to the gapped sites (by coding them as binary character data – presence/absence, or as in the MLε method), and (5) in general, the accuracy of phylogenetic inference depended upon the amount of available data when the gaps resulted from mainly deletion events, and the amount of missing data when insertion events were equally likely to have caused the alignment gaps. Conclusion When gaps in an alignment are a consequence of indel events in the evolution of the sequences, the accuracy of phylogenetic analysis is likely to improve if: (1) alignment gaps are categorized as arising from insertion events or deletion events and then treated separately in the analysis, (2) the evolutionary signal provided by indels is harnessed in the phylogenetic analysis, and (3) methods that utilize the phylogenetic signal in indels are developed for distance methods too. When the true homology is known and the amount of gaps is 20 percent of the alignment length or less, the methods used in this study are likely to yield trees with 90–100 percent accuracy. PMID:19698168

Disorders of dysregulated signal traffic through the RAS-MAPK pathway: phenotypic spectrum and molecular mechanisms.

PubMed

Tartaglia, Marco; Gelb, Bruce D

2010-12-01

RAS GTPases control a major signaling network implicated in several cellular functions, including cell fate determination, proliferation, survival, differentiation, migration, and senescence. Within this network, signal flow through the RAF-MEK-ERK pathway-the first identified mitogen-associated protein kinase (MAPK) cascade-mediates early and late developmental processes controlling morphology determination, organogenesis, synaptic plasticity, and growth. Signaling through the RAS-MAPK cascade is tightly controlled; and its enhanced activation represents a well-known event in oncogenesis. Unexpectedly, in the past few years, inherited dysregulation of this pathway has been recognized as the cause underlying a group of clinically related disorders sharing facial dysmorphism, cardiac defects, reduced postnatal growth, ectodermal anomalies, variable cognitive deficits, and susceptibility to certain malignancies as major features. These disorders are caused by heterozygosity for mutations in genes encoding RAS proteins, regulators of RAS function, modulators of RAS interaction with effectors, or downstream signal transducers. Here, we provide an overview of the phenotypic spectrum associated with germline mutations perturbing RAS-MAPK signaling, the unpredicted molecular mechanisms converging toward the dysregulation of this signaling cascade, and major genotype-phenotype correlations. © 2010 New York Academy of Sciences.

Exploration of the association rules mining technique for the signal detection of adverse drug events in spontaneous reporting systems.

PubMed

Wang, Chao; Guo, Xiao-Jing; Xu, Jin-Fang; Wu, Cheng; Sun, Ya-Lin; Ye, Xiao-Fei; Qian, Wei; Ma, Xiu-Qiang; Du, Wen-Min; He, Jia

2012-01-01

The detection of signals of adverse drug events (ADEs) has increased because of the use of data mining algorithms in spontaneous reporting systems (SRSs). However, different data mining algorithms have different traits and conditions for application. The objective of our study was to explore the application of association rule (AR) mining in ADE signal detection and to compare its performance with that of other algorithms. Monte Carlo simulation was applied to generate drug-ADE reports randomly according to the characteristics of SRS datasets. Thousand simulated datasets were mined by AR and other algorithms. On average, 108,337 reports were generated by the Monte Carlo simulation. Based on the predefined criterion that 10% of the drug-ADE combinations were true signals, with RR equaling to 10, 4.9, 1.5, and 1.2, AR detected, on average, 284 suspected associations with a minimum support of 3 and a minimum lift of 1.2. The area under the receiver operating characteristic (ROC) curve of the AR was 0.788, which was equivalent to that shown for other algorithms. Additionally, AR was applied to reports submitted to the Shanghai SRS in 2009. Five hundred seventy combinations were detected using AR from 24,297 SRS reports, and they were compared with recognized ADEs identified by clinical experts and various other sources. AR appears to be an effective method for ADE signal detection, both in simulated and real SRS datasets. The limitations of this method exposed in our study, i.e., a non-uniform thresholds setting and redundant rules, require further research.

Search for gamma-ray events in the BATSE data base

NASA Technical Reports Server (NTRS)

Lewin, Walter

1994-01-01

We find large location errors and error radii in the locations of channel 1 Cygnus X-1 events. These errors and their associated uncertainties are a result of low signal-to-noise ratios (a few sigma) in the two brightest detectors for each event. The untriggered events suffer from similarly low signal-to-noise ratios, and their location errors are expected to be at least as large as those found for Cygnus X-1 with a given signal-to-noise ratio. The statistical error radii are consistent with those found for Cygnus X-1 and with the published estimates. We therefore expect approximately 20 - 30 deg location errors for the untriggered events. Hence, many of the untriggered events occurring within a few months of the triggered activity from SGR 1900 plus 14 are indeed consistent with the SGR source location, although Cygnus X-1 is also a good candidate.

The Run-up to Volcanic Eruption Unveiled by Forensic Petrology and Geophysical Observations

NASA Astrophysics Data System (ADS)

Rasmussen, D. J.; Plank, T. A.; Roman, D. C.

2017-12-01

Volcanoes often warn of impending eruptions. However, one of the greatest challenges in volcano research is translating precursory geophysical signals into physical magmatic processes. Petrology offers powerful tools to study eruption run-up that benefit from direct response to magmatic forcings. Developing these tools, and tying them to geophysical observations, will help us identify eruption triggers (e.g., magmatic recharge, gas build-up, tectonic events) and understand the significance of monitored signals of unrest. We present an overview of petrologic tools used for studying eruption run-up, highlighting results from our study of the 1999 eruption of Shishaldin volcano. Olivine crystals contain chemical gradients, the consequence of diffusion following magma mixing events, which is modeled to determine mixing timescales. Modeled timescales provide strong evidence for at least three mixing events, which were triggered by magmatic recharge. Petrologic barometers indicate these events occurred at very shallow depths (within the volcanic edifice). The first mixing event occurred nine months before eruption, which was signaled by a swarm of deep-long period earthquake. Minor recharge events followed over two months, which are indicated by a second deep-long period earthquake swarm and a change in the local stress orientation measured by shear-wave splitting. Following these events, the system was relatively quiet until a large mixing event occurred 45 days prior to eruption, which was heralded by a large earthquake (M5.2). Following this event, geophysical signals of unrest intensified and became continuous. The final mixing event, beginning roughly a week before eruption, represents the final perturbation to the system before eruption. Our findings point to a relatively long run-up, which was subtle at first and intensified several weeks before eruption. This study highlights the strong link between geophysical signals of volcanic unrest and magmatic events, and helps open the door for the application of forensic petrology to unmonitored eruptions.

Gravitational Microlensing Events as a Target for the SETI project

NASA Astrophysics Data System (ADS)

Rahvar, Sohrab

2016-09-01

The detection of signals from a possible extrasolar technological civilization is one of the most challenging efforts of science. In this work, we propose using natural telescopes made of single or binary gravitational lensing systems to magnify leakage of electromagnetic signals from a remote planet that harbors Extraterrestrial Intelligent (ETI) technology. Currently, gravitational microlensing surveys are monitoring a large area of the Galactic bulge to search for microlensing events, finding more than 2000 events per year. These lenses are capable of playing the role of natural telescopes, and, in some instances, they can magnify radio band signals from planets orbiting around the source stars in gravitational microlensing systems. Assuming that the frequency of electromagnetic waves used for telecommunication in ETIs is similar to ours, we propose follow-up observation of microlensing events with radio telescopes such as the Square Kilometre Array (SKA), the Low Frequency Demonstrators, and the Mileura Wide-Field Array. Amplifying signals from the leakage of broadcasting by an Earth-like civilization will allow us to detect them as far as the center of the Milky Way galaxy. Our analysis shows that in binary microlensing systems, the probability of amplification of signals from ETIs is more than that in single microlensing events. Finally, we propose the use of the target of opportunity mode for follow-up observations of binary microlensing events with SKA as a new observational program for searching ETIs. Using optimistic values for the factors of the Drake equation provides detection of about one event per year.

Interactions Between Depression and Lower Urinary Tract Symptoms: The Role of Adverse Life Events and Inflammatory Mechanisms. Results From the European Male Ageing Study.

PubMed

Castellini, Giovanni; Wu, Frederick C W; Finn, Joseph D; OʼNeill, Terrence W; Lean, Michael E J; Pendleton, Neil; Rastrelli, Giulia; Rutter, Martin K; Gacci, Mauro; Ricca, Valdo; Maggi, Mario

2016-01-01

Depression and lower urinary tract symptoms (LUTSs) have been found to co-occur among aging men. The present study attempted to clarify the nature of this relationship, considering adverse life events as potential moderators and the inflammation as an underlying biological mechanism. The relationship between depression and LUTS was evaluated using data from the European Male Ageing Study, the largest multicenter population-based study of aging in European men. The sample included 3369 men who were assessed by means of several self-reported questionnaires, including the Beck Depression Inventory-II, the International Prostate Symptom Score, and the Adverse Life Events Scale. Participants were asked to provide information regarding general health and life-style, and medical comorbidities. Biological measures including prostate-specific antigen, testosterone, and C-reactive protein were measured. LUTS and depressive symptoms were correlated (R = 0.32, β = .10, p < .001), even after adjusting for life-style, psychological, and medical variables. A history of adverse life events was associated with both higher LUTS and Beck Depression Inventory scores. Furthermore, adverse life events moderated the LUTS-depression association (F = 22.62, b = 0.061, p < .001), which increased as a function of the number of life events. C-reactive protein was found to mediate the LUTS-depression association. This mediation effect was moderated by number of adverse life events. Participants with a history of adverse life events represent a vulnerable population in whom the association between somatic and depressive symptoms is stronger. One of the biological mechanisms underlying this association could be an activation of the central inflammatory signaling pathways.

Impact of Source Region on the delta18 O signal in snow: A case study from Mount Wrangell Alaska

NASA Technical Reports Server (NTRS)

Moore, G.W.K.; Field, Robert D.; Benson, Carl S.

2016-01-01

The stable isotopic composition of water in ice cores is an important source of information on past climate variability. At its simplest level, the underlying assumption is that there is an empirical relationship between the normalized difference in the concentration for these stable isotopes and a specified local temperature at the ice core site. There are, however, nonlocal processes, such as a change in source region or a change in the atmospheric pathway, which can impact the stable isotope signal, thereby complicating its use as a proxy for temperature. In this paper, the importance of these nonlocal processes are investigated through the analysis of the synoptic-scale circulation during a snowfall event at the summit of Mount Wrangell (62 deg N, 144 deg W; 4300 m MSL) in south-central Alaska. During this event there was, over a 1-day period in which the local temperature was approximately constant, a change in delta18 O that exceeded half that normally seen to occur in the region between summer and winter. As shall be shown, this arose from a change in the source region, from the subtropical eastern Pacific to northeastern Asia, for the snow that fell on Mount Wrangell during the event.

Acoustic Events and “Optophonic” Cochlear Responses Induced by Pulsed Near-Infrared LASER

PubMed Central

Maier, Hannes; Richter, Claus-Peter; Kral, Andrej

2012-01-01

Optical stimulation of neural tissue within the cochlea was described as a possible alternative to electrical stimulation. Most optical stimulation was performed with pulsed lasers operating with near-infrared (NIR) light and in thermal confinement. Under these conditions, the coexistence of laser-induced optoacoustic stimulation of the cochlea (“optophony”) has not been analyzed yet. This study demonstrates that pulsed 1850-nm laser light used for neural stimulation also results in sound pressure levels up to 62 dB peak-to-peak equivalent sound pressure level (SPL) in air. The sound field was confined to a small volume along the laser beam. In dry nitrogen, laser-induced acoustic events disappeared. Hydrophone measurements demonstrated pressure waves for laser fibers immersed in water. In hearing rats, laser-evoked signals were recorded from the cochlea without targeting neural tissue. The signals showed a two-domain response differing in amplitude and latency functions, as well as sensitivity to white-noise masking. The first component had characteristics of a cochlear microphonic potential, and the second component was characteristic for a compound action potential. The present data demonstrate that laser-evoked acoustic events can stimulate a hearing cochlea. Whenever optical stimulation is used, care must be taken to distinguish between such “optophony” and the true optoneural response. PMID:21278011

Spatial focalization of pheromone/MAPK signaling triggers commitment to cell–cell fusion

PubMed Central

Merlini, Laura

2016-01-01

Cell fusion is universal in eukaryotes for fertilization and development, but what signals this process is unknown. Here, we show in Schizosaccharomyces pombe that fusion does not require a dedicated signal but is triggered by spatial focalization of the same pheromone–GPCR (G-protein-coupled receptor)–MAPK signaling cascade that drives earlier mating events. Autocrine cells expressing the receptor for their own pheromone trigger fusion attempts independently of cell–cell contact by concentrating pheromone release at the fusion focus, a dynamic actin aster underlying the secretion of cell wall hydrolases. Pheromone receptor and MAPK cascade are similarly enriched at the fusion focus, concomitant with fusion commitment in wild-type mating pairs. This focalization promotes cell fusion by immobilizing the fusion focus, thus driving local cell wall dissolution. We propose that fusion commitment is imposed by a local increase in MAPK concentration at the fusion focus, driven by a positive feedback between fusion focus formation and focalization of pheromone release and perception. PMID:27798845

Notch Promotes Dynamin-Dependent Endocytosis of Nephrin

PubMed Central

Waters, Aoife M.; Wu, Megan Yi Jun; Huang, Yi-Wei; Liu, Guang Ying; Holmyard, Doug; Onay, Tuncer; Jones, Nina; Egan, Sean E.; Robinson, Lisa A.

2012-01-01

Notch signaling in podocytes causes proteinuria and glomerulosclerosis in humans and rodents, but the underlying mechanism remains unknown. Here, we analyzed morphologic, molecular, and cellular events before the onset of proteinuria in newborn transgenic mice that express activated Notch in podocytes. Immunohistochemistry revealed a loss of the slit diaphragm protein nephrin exclusively in podocytes expressing activated Notch. Podocyte-specific deletion of Rbpj, which is essential for canonical Notch signaling, prevented this loss of nephrin. Overexpression of activated Notch decreased cell surface nephrin and increased cytoplasmic nephrin in transfected HEK293T cells; pharmacologic inhibition of dynamin, but not depletion of cholesterol, blocked these effects on nephrin, suggesting that Notch promotes dynamin-dependent, raft-independent endocytosis of nephrin. Supporting an association between Notch signaling and nephrin trafficking, electron microscopy revealed shortened podocyte foot processes and fewer slit diaphragms among the transgenic mice compared with controls. These data suggest that Notch signaling induces endocytosis of nephrin, thereby triggering the onset of proteinuria. PMID:22052054

Neurodegeneration in Alzheimer disease: role of amyloid precursor protein and presenilin 1 intracellular signaling.

PubMed

Nizzari, Mario; Thellung, Stefano; Corsaro, Alessandro; Villa, Valentina; Pagano, Aldo; Porcile, Carola; Russo, Claudio; Florio, Tullio

2012-01-01

Alzheimer disease (AD) is a heterogeneous neurodegenerative disorder characterized by (1) progressive loss of synapses and neurons, (2) intracellular neurofibrillary tangles, composed of hyperphosphorylated Tau protein, and (3) amyloid plaques. Genetically, AD is linked to mutations in few proteins amyloid precursor protein (APP) and presenilin 1 and 2 (PS1 and PS2). The molecular mechanisms underlying neurodegeneration in AD as well as the physiological function of APP are not yet known. A recent theory has proposed that APP and PS1 modulate intracellular signals to induce cell-cycle abnormalities responsible for neuronal death and possibly amyloid deposition. This hypothesis is supported by the presence of a complex network of proteins, clearly involved in the regulation of signal transduction mechanisms that interact with both APP and PS1. In this review we discuss the significance of novel finding related to cell-signaling events modulated by APP and PS1 in the development of neurodegeneration.

Composite regulation of ERK activity dynamics underlying tumour-specific traits in the intestine.

PubMed

Muta, Yu; Fujita, Yoshihisa; Sumiyama, Kenta; Sakurai, Atsuro; Taketo, M Mark; Chiba, Tsutomu; Seno, Hiroshi; Aoki, Kazuhiro; Matsuda, Michiyuki; Imajo, Masamichi

2018-06-05

Acting downstream of many growth factors, extracellular signal-regulated kinase (ERK) plays a pivotal role in regulating cell proliferation and tumorigenesis, where its spatiotemporal dynamics, as well as its strength, determine cellular responses. Here, we uncover the ERK activity dynamics in intestinal epithelial cells (IECs) and their association with tumour characteristics. Intravital imaging identifies two distinct modes of ERK activity, sustained and pulse-like activity, in IECs. The sustained and pulse-like activities depend on ErbB2 and EGFR, respectively. Notably, activation of Wnt signalling, the earliest event in intestinal tumorigenesis, augments EGFR signalling and increases the frequency of ERK activity pulses through controlling the expression of EGFR and its regulators, rendering IECs sensitive to EGFR inhibition. Furthermore, the increased pulse frequency is correlated with increased cell proliferation. Thus, ERK activity dynamics are defined by composite inputs from EGFR and ErbB2 signalling in IECs and their alterations might underlie tumour-specific sensitivity to pharmacological EGFR inhibition.

Smad2 and Smad3 have differential sensitivity in relaying TGFβ signaling and inversely regulate early lineage specification

PubMed Central

Liu, Ling; Liu, Xu; Ren, Xudong; Tian, Yue; Chen, Zhenyu; Xu, Xiangjie; Du, Yanhua; Jiang, Cizhong; Fang, Yujiang; Liu, Zhongliang; Fan, Beibei; Zhang, Quanbin; Jin, Guohua; Yang, Xiao; Zhang, Xiaoqing

2016-01-01

The transforming growth factor beta (TGFβ) related signaling is one of the most important signaling pathways regulating early developmental events. Smad2 and Smad3 are structurally similar and it is mostly considered that they are equally important in mediating TGFβ signals. Here, we show that Smad3 is an insensitive TGFβ transducer as compared with Smad2. Smad3 preferentially localizes within the nucleus and is thus sequestered from membrane signaling. The ability of Smad3 in oligomerization with Smad4 upon agonist stimulation is also impaired given its unique linker region. Smad2 mediated TGFβ signaling plays a crucial role in epiblast development and patterning of three germ layers. However, signaling unrelated nuclear localized Smad3 is dispensable for TGFβ signaling-mediated epiblast specification, but important for early neural development, an event blocked by TGFβ/Smad2 signaling. Both Smad2 and Smad3 bind to the conserved Smads binding element (SBE), but they show nonoverlapped target gene binding specificity and differential transcriptional activity. We conclude that Smad2 and Smad3 possess differential sensitivities in relaying TGFβ signaling and have distinct roles in regulating early developmental events. PMID:26905010

Smad2 and Smad3 have differential sensitivity in relaying TGFβ signaling and inversely regulate early lineage specification.

PubMed

Liu, Ling; Liu, Xu; Ren, Xudong; Tian, Yue; Chen, Zhenyu; Xu, Xiangjie; Du, Yanhua; Jiang, Cizhong; Fang, Yujiang; Liu, Zhongliang; Fan, Beibei; Zhang, Quanbin; Jin, Guohua; Yang, Xiao; Zhang, Xiaoqing

2016-02-24

The transforming growth factor beta (TGFβ) related signaling is one of the most important signaling pathways regulating early developmental events. Smad2 and Smad3 are structurally similar and it is mostly considered that they are equally important in mediating TGFβ signals. Here, we show that Smad3 is an insensitive TGFβ transducer as compared with Smad2. Smad3 preferentially localizes within the nucleus and is thus sequestered from membrane signaling. The ability of Smad3 in oligomerization with Smad4 upon agonist stimulation is also impaired given its unique linker region. Smad2 mediated TGFβ signaling plays a crucial role in epiblast development and patterning of three germ layers. However, signaling unrelated nuclear localized Smad3 is dispensable for TGFβ signaling-mediated epiblast specification, but important for early neural development, an event blocked by TGFβ/Smad2 signaling. Both Smad2 and Smad3 bind to the conserved Smads binding element (SBE), but they show nonoverlapped target gene binding specificity and differential transcriptional activity. We conclude that Smad2 and Smad3 possess differential sensitivities in relaying TGFβ signaling and have distinct roles in regulating early developmental events.

Remote detection of weak aftershocks of the DPRK underground explosions using waveform cross correlation

NASA Astrophysics Data System (ADS)

Le Bras, R.; Rozhkov, M.; Bobrov, D.; Kitov, I. O.; Sanina, I.

2017-12-01

Association of weak seismic signals generated by low-magnitude aftershocks of the DPRK underground tests into event hypotheses represent a challenge for routine automatic and interactive processing at the International Data Centre (IDC) of the Comprehensive Nuclear-Test-Ban Treaty Organization, due to the relatively low station density of the International Monitoring System (IMS) seismic network. Since 2011, as an alternative, the IDC has been testing various prototype techniques of signal detection and event creation based on waveform cross correlation. Using signals measured by seismic stations of the IMS from DPRK explosions as waveform templates, the IDC detected several small (estimated mb between 2.2 and 3.6) seismic events after two DPRK tests conducted on September 9, 2016 and September 3, 2017. The obtained detections were associated with reliable event hypothesis and then used to locate these events relative to the epicenters of the DPRK explosions. We observe high similarity of the detected signals with the corresponding waveform templates. The newly found signals also correlate well between themselves. In addition, the values of the signal-to-noise ratios (SNR) estimated using the traces of cross correlation coefficients, increase with template length (from 5 s to 150 s), providing strong evidence in favour of their spatial closeness, which allows interpreting them as explosion aftershocks. We estimated the relative magnitudes of all aftershocks using the ratio of RMS amplitudes of the master and slave signal in the cross correlation windows characterized by the highest SNR. Additional waveform data from regional non-IMS stations MDJ and SEHB provide independent validation of these aftershock hypotheses. Since waveform templates from any single master event may be sub-efficient at some stations, we have also developed a method of joint usage of the DPRK and the biggest aftershocks templates to build more robust event hypotheses.

Simulated Performance of the Orbiting Wide-angle Light Collectors (OWL) Experiment

NASA Technical Reports Server (NTRS)

Krizmanic, J. F.; Whitaker, Ann F. (Technical Monitor)

2001-01-01

The Orbiting Wide-angle Light collectors (OWL) experiment is in NASA's mid-term strategic plan and will stereoscopically image, from equatorial orbit, the air fluorescence signal generated by airshowers induced by the ultrahigh energy (E greater than few x 10(exp 19) eV) component of the cosmic radiation. The use of a space-based platform enables an extremely large event acceptance aperture and thus will allow a high statistics measurement of these rare events. Detailed Monte Carlo simulations are required to quantify the physics potential of the mission as well as optimize the instrumental parameters. This paper reports on the results of the GSFC Monte Carlo simulation for two different, OWL instrument baseline designs. These results indicate that, assuming a continuation of the cosmic ray spectrum (theta approximately E(exp -2.75), OWL could have an event rate of 4000 events/year with E greater than or equal to 10(exp 20) eV. Preliminary results, based upon these Monte Carlo simulations, indicate that events can be accurately reconstructed in the detector focal plane arrays for the OWL instrument baseline designs under consideration.

The upper bound to the Relative Reporting Ratio—a measure of the impact of the violation of hidden assumptions underlying some disproportionality methods used in signal detection

PubMed Central

Van Holle, Lionel; Bauchau, Vincent

2014-01-01

Purpose For disproportionality measures based on the Relative Reporting Ratio (RRR) such as the Information Component (IC) and the Empirical Bayesian Geometrical Mean (EBGM), each product and event is assumed to represent a negligible fraction of the spontaneous report database (SRD). Here, we provide the tools for allowing signal detection experts to assess the consequence of the violation of this assumption on their specific SRD. Methods For each product–event pair (P–E), a worst-case scenario associated all the reported events-of-interest with the product of interest. The values of the RRR under this scenario were measured for different sets of stratification factors using the GlaxoSmithKline vaccines SRD. These values represent the RRR upper bound that RRR cannot exceed whatever the true strength of association. Results Depending on the choice of stratification factors, the RRR could not exceed an upper bound of 2 for up to 2.4% of the P–Es. For Engerix™, 23.4% of all reports in the SDR, the RRR could not exceed an upper bound of 2 for up to 13.8% of pairs. For the P–E Rotarix™-Intussusception, the choice of stratification factors impacted the upper bound to RRR: from 52.5 for an unstratified RRR to 2.0 for a fully stratified RRR. Conclusions The quantification of the upper bound can indicate whether measures such as EBGM, IC, or RRR can be used for SRD for which products or events represent a non-negligible fraction of the entire SRD. In addition, at the level of the product or P–E, it can also highlight detrimental impact of overstratification. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:24395594

Association rule mining in the US Vaccine Adverse Event Reporting System (VAERS).

PubMed

Wei, Lai; Scott, John

2015-09-01

Spontaneous adverse event reporting systems are critical tools for monitoring the safety of licensed medical products. Commonly used signal detection algorithms identify disproportionate product-adverse event pairs and may not be sensitive to more complex potential signals. We sought to develop a computationally tractable multivariate data-mining approach to identify product-multiple adverse event associations. We describe an application of stepwise association rule mining (Step-ARM) to detect potential vaccine-symptom group associations in the US Vaccine Adverse Event Reporting System. Step-ARM identifies strong associations between one vaccine and one or more adverse events. To reduce the number of redundant association rules found by Step-ARM, we also propose a clustering method for the post-processing of association rules. In sample applications to a trivalent intradermal inactivated influenza virus vaccine and to measles, mumps, rubella, and varicella (MMRV) vaccine and in simulation studies, we find that Step-ARM can detect a variety of medically coherent potential vaccine-symptom group signals efficiently. In the MMRV example, Step-ARM appears to outperform univariate methods in detecting a known safety signal. Our approach is sensitive to potentially complex signals, which may be particularly important when monitoring novel medical countermeasure products such as pandemic influenza vaccines. The post-processing clustering algorithm improves the applicability of the approach as a screening method to identify patterns that may merit further investigation. Copyright © 2015 John Wiley & Sons, Ltd.

Nuclear calcium is required for human T cell activation

PubMed Central

Samstag, Yvonne

2016-01-01

Calcium signals in stimulated T cells are generally considered single entities that merely trigger immune responses, whereas costimulatory events specify the type of reaction. Here we show that the “T cell calcium signal” is a composite signal harboring two distinct components that antagonistically control genomic programs underlying the immune response. Using human T cells from healthy individuals, we establish nuclear calcium as a key signal in human T cell adaptogenomics that drives T cell activation and is required for signaling to cyclic adenosine monophosphate response element–binding protein and the induction of CD25, CD69, interleukin-2, and γ-interferon. In the absence of nuclear calcium signaling, cytosolic calcium activating nuclear factor of activated T cells translocation directed the genomic response toward enhanced expression of genes that negatively modulate T cell activation and are associated with a hyporesponsive state. Thus, nuclear calcium controls the T cell fate decision between a proliferative immune response and tolerance. Modulators of nuclear calcium–driven transcription may be used to develop a new type of pro-tolerance immunosuppressive therapy. PMID:27810914

The effects of lossy compression on diagnostically relevant seizure information in EEG signals.

PubMed

Higgins, G; McGinley, B; Faul, S; McEvoy, R P; Glavin, M; Marnane, W P; Jones, E

2013-01-01

This paper examines the effects of compression on EEG signals, in the context of automated detection of epileptic seizures. Specifically, it examines the use of lossy compression on EEG signals in order to reduce the amount of data which has to be transmitted or stored, while having as little impact as possible on the information in the signal relevant to diagnosing epileptic seizures. Two popular compression methods, JPEG2000 and SPIHT, were used. A range of compression levels was selected for both algorithms in order to compress the signals with varying degrees of loss. This compression was applied to the database of epileptiform data provided by the University of Freiburg, Germany. The real-time EEG analysis for event detection automated seizure detection system was used in place of a trained clinician for scoring the reconstructed data. Results demonstrate that compression by a factor of up to 120:1 can be achieved, with minimal loss in seizure detection performance as measured by the area under the receiver operating characteristic curve of the seizure detection system.

Processing of the Liquid Xenon calorimeter's signals for timing measurements

NASA Astrophysics Data System (ADS)

Epshteyn, L. B.; Yudin, Yu V.

2014-09-01

One of the goals of the Cryogenic Magnetic Detector at Budker Institute of Nuclear Physics SB RAS (Novosibirsk, Russia) is a study of nucleons production in electron-positron collisions near threshold. The neutron-antineutron pair production events can be detected only by the calorimeters. In the barrel calorimeter the antineutron annihilation typically occurs by 5 ns or later after beams crossing. For identification of such events it is necessary to measure the time of flight of particles to the LXe-calorimeter with accuracy of about 3 ns. The LXe-calorimeter consists of 14 layers of ionization chambers with anode and cathode readout. The duration of charge collection to the anodes is about 4.5 mks, while the required accuracy of measuring of the signal arrival time is less than 1/1000 of that. Besides, the signals' shapes differ substantially from event to event, so the signal arrival time is measured in two stages. At the first stage, the signal arrival time is determined with an accuracy of 1-2 discretization periods, and initial values of parameters for subsequent fitting procedure are calculated. At the second stage, the signal arrival time is determined with the required accuracy by means of fitting of the signal waveform with a template waveform. To implement that, a special electronics has been developed which performs waveform digitization and On-Line measurement of signals' arrival times and amplitudes.

Broadband analysis of landslides seismic signal : example of the Oso-Steelhead landslide and other recent events

NASA Astrophysics Data System (ADS)

Hibert, C.; Stark, C. P.; Ekstrom, G.

2014-12-01

Landslide failures on the scale of mountains are spectacular, dangerous, and spontaneous, making direct observations hard to obtain. Measurement of their dynamic properties during runout is a high research priority, but a logistical and technical challenge. Seismology has begun to help in several important ways. Taking advantage of broadband seismic stations, recent advances now allow: (i) the seismic detection and location of large landslides in near-real-time, even for events in very remote areas that may have remain undetected, such as the 2014 Mt La Perouse supraglacial failure in Alaska; (ii) inversion of long-period waves generated by large landslides to yield an estimate of the forces imparted by the bulk accelerating mass; (iii) inference of the landslide mass, its center-of-mass velocity over time, and its trajectory.Key questions persist, such as: What can the short-period seismic data tell us about the high-frequency impacts taking place within the granular flow and along its boundaries with the underlying bedrock? And how does this seismicity relate to the bulk acceleration of the landslide and the long-period seismicity generated by it?Our recent work on the joint analysis of short- and long-period seismic signals generated by past and recent events, such as the Bingham Canyon Mine and the Oso-Steelhead landslides, provides new insights to tackle these issues. Qualitative comparison between short-period signal features and kinematic parameters inferred from long-period surface wave inversion helps to refine interpretation of the source dynamics and to understand the different mechanisms for the origin of the short-period wave radiation. Our new results also suggest that quantitative relationships can be derived from this joint analysis, in particular between the short-period seismic signal envelope and the inferred momentum of the center-of-mass. In the future, these quantitative relationships may help to constrain and calibrate parameters used in inversion or simulation of long-period waves generated by landslides. Relating the center-of-mass dynamics to the short-period seismic signal might also yield a new means to estimate kinematic parameters for the smaller events that generate too weak long-period seismic waves to allow inversion or simulation of the seismic source.

Seismic Wave Velocity in the Subducted Oceanic Crust from Autocorrelation of Tectonic Tremor Signals

NASA Astrophysics Data System (ADS)

Ducellier, A.; Creager, K.

2017-12-01

Hydration and dehydration of minerals in subduction zones play a key role in the geodynamic processes that generate seismicity and that allow tectonic plates to subduct. Detecting the presence of water in the subducted plate is thus crucial to better understand the seismogenesis and the consequent seismic hazard. A landward dipping, low velocity layer has been detected in most subduction zones. In Cascadia, this low velocity zone is characterized by a low S-wave velocity and a very high Poisson's ratio, which has been interpreted as high pore-fluid pressure in the upper half part of the subducted oceanic crust. Most previous studies were based on seismic reflection imaging, receiver function analysis, or body wave tomography, with seismic sources located far from the low velocity zone. In contrast, the sources of the tectonic tremors generated during Episodic Tremor and Slip (ETS) events are located on the plate boundary. As the sources of the tremors are much closer to the low velocity zone, seismic waves recorded during ETS events should illuminate the area with greater precision. Most methods to detect and locate tectonic tremors and low-frequency earthquakes are based on the cross correlation of seismic signals; either signals at the same station for different events, or the same event at different stations. We use the autocorrelation of the seismic signal recorded by eight arrays of stations, located in the Olympic Peninsula, Washington. Each tremor, assumed to be on the plate boundary, generates a direct wave and reflected and converted waves from both the strong shear-wave velocity contrast in the mid-oceanic crust, and from the Moho of the subducted oceanic crust. The time lag between the arrivals of these different waves at a seismic station corresponds to a peak of amplitude on the autocorrelation signals. Using the time lags observed for different locations of the tremor source, we intend to invert for the seismic wave velocity of the subducted oceanic crust under the arrays. Identifying zones with lower S-wave velocity and a high Poisson's ratio will then help detecting the presence of water in the subducted oceanic crust. Our ultimate goal is contributing to a better understanding of the mechanism of ETS and subduction zone processes.

Calcium signaling in mammalian egg activation and embryo development: Influence of subcellular localization

PubMed Central

Miao, Yi-Liang; Williams, Carmen J.

2012-01-01

Calcium (Ca2+) signals drive the fundamental events surrounding fertilization and the activation of development in all species examined to date. Initial studies of Ca2+ signaling at fertilization in marine animals were tightly linked to new discoveries of bioluminescent proteins and their use as fluorescent Ca2+ sensors. Since that time, there has been rapid progress in our understanding of the key functions for Ca2+ in many cell types and the impact of cellular localization on Ca2+ signaling pathways. In this review, which focuses on mammalian egg activation, we consider how Ca2+ is regulated and stored at different stages of oocyte development and examine the functions of molecules that serve as both regulators of Ca2+ release and effectors of Ca2+ signals. We then summarize studies exploring how Ca2+ directs downstream effectors mediating both egg activation and later signaling events required for successful preimplantation embryo development. Throughout this review, we focus attention on how localization of Ca2+ signals influences downstream signaling events, and attempt to highlight gaps in our knowledge that are ripe areas for future research. PMID:22888043

Crosstalk of Signaling and Metabolism Mediated by the NAD(+)/NADH Redox State in Brain Cells.

PubMed

Winkler, Ulrike; Hirrlinger, Johannes

2015-12-01

The energy metabolism of the brain has to be precisely adjusted to activity to cope with the organ's energy demand, implying that signaling regulates metabolism and metabolic states feedback to signaling. The NAD(+)/NADH redox state constitutes a metabolic node well suited for integration of metabolic and signaling events. It is affected by flux through metabolic pathways within a cell, but also by the metabolic state of neighboring cells, for example by lactate transferred between cells. Furthermore, signaling events both in neurons and astrocytes have been reported to change the NAD(+)/NADH redox state. Vice versa, a number of signaling events like astroglial Ca(2+) signals, neuronal NMDA-receptors as well as the activity of transcription factors are modulated by the NAD(+)/NADH redox state. In this short review, this bidirectional interdependence of signaling and metabolism involving the NAD(+)/NADH redox state as well as its potential relevance for the physiology of the brain and the whole organism in respect to blood glucose regulation and body weight control are discussed.

Automatic detection of snow avalanches in continuous seismic data using hidden Markov models

NASA Astrophysics Data System (ADS)

Heck, Matthias; Hammer, Conny; van Herwijnen, Alec; Schweizer, Jürg; Fäh, Donat

2018-01-01

Snow avalanches generate seismic signals as many other mass movements. Detection of avalanches by seismic monitoring is highly relevant to assess avalanche danger. In contrast to other seismic events, signals generated by avalanches do not have a characteristic first arrival nor is it possible to detect different wave phases. In addition, the moving source character of avalanches increases the intricacy of the signals. Although it is possible to visually detect seismic signals produced by avalanches, reliable automatic detection methods for all types of avalanches do not exist yet. We therefore evaluate whether hidden Markov models (HMMs) are suitable for the automatic detection of avalanches in continuous seismic data. We analyzed data recorded during the winter season 2010 by a seismic array deployed in an avalanche starting zone above Davos, Switzerland. We re-evaluated a reference catalogue containing 385 events by grouping the events in seven probability classes. Since most of the data consist of noise, we first applied a simple amplitude threshold to reduce the amount of data. As first classification results were unsatisfying, we analyzed the temporal behavior of the seismic signals for the whole data set and found that there is a high variability in the seismic signals. We therefore applied further post-processing steps to reduce the number of false alarms by defining a minimal duration for the detected event, implementing a voting-based approach and analyzing the coherence of the detected events. We obtained the best classification results for events detected by at least five sensors and with a minimal duration of 12 s. These processing steps allowed identifying two periods of high avalanche activity, suggesting that HMMs are suitable for the automatic detection of avalanches in seismic data. However, our results also showed that more sensitive sensors and more appropriate sensor locations are needed to improve the signal-to-noise ratio of the signals and therefore the classification.

Multi-Phenomenological Analysis of the 12 August 2015 Tianjin, China Chemical Explosion

NASA Astrophysics Data System (ADS)

Pasyanos, M.; Kim, K.; Park, J.; Stump, B. W.; Hayward, C.; Che, I. Y.; Zhao, L.; Myers, S. C.

2016-12-01

We perform a multi-phenomenological analysis of the massive near-surface chemical explosions that occurred in Tianjin, China on 12 August 2015. A recent assessment of these events was performed by Zhao et al. (2016) using local (< 100 km) seismic data. This study considers a regional assessment of the same sequence in the absence of having any local data. We provide additional insight by combining regional seismic analysis with the use of infrasound signals and an assessment of the event crater. Event locations using infrasound signals recorded at Korean and IMS arrays are estimated based on the Bayesian Infrasonic Source Location (BISL) method (Modrak et al., 2010), and improved with azimuthal corrections using a raytracing (Blom and Waxler, 2012) and the Ground-to-Space (G2S) atmospheric models (Drob et al., 2003). The location information provided from the infrasound signals is then merged with the regional seismic arrivals to produce a joint event location. The yields of the events are estimated from seismic and infrasonic observations. Seismic waveform envelope method (Pasyanos et al., 2012) including the free surface effect (Pasyanos and Ford, 2015) is applied to regional seismic signals. Waveform inversion method (Kim and Rodgers, 2016) is used for infrasound signals. A combination of the seismic and acoustic signals can provide insights on the energy partitioning and break the tradeoffs between the yield and the depth/height of explosions, resulting in a more robust estimation of event yield. The yield information from the different phenomenologies are combined through the use of likelihood functions.

Automated Electroglottographic Inflection Events Detection. A Pilot Study.

PubMed

Codino, Juliana; Torres, María Eugenia; Rubin, Adam; Jackson-Menaldi, Cristina

2016-11-01

Vocal-fold vibration can be analyzed in a noninvasive way by registering impedance changes within the glottis, through electroglottography. The morphology of the electroglottographic (EGG) signal is related to different vibratory patterns. In the literature, a characteristic knee in the descending portion of the signal has been reported. Some EGG signals do not exhibit this particular knee and have other types of events (inflection events) throughout the ascending and/or descending portion of the vibratory cycle. The goal of this work is to propose an automatic method to identify and classify these events. A computational algorithm was developed based on the mathematical properties of the EGG signal, which detects and reports events throughout the contact phase. Retrospective analysis of EGG signals obtained during routine voice evaluation of adult individuals with a variety of voice disorders was performed using the algorithm as well as human raters. Two judges, both experts in clinical voice analysis, and three general speech pathologists performed manual and visual evaluation of the sample set. The results obtained by the automatic method were compared with those of the human raters. Statistical analysis revealed a significant level of agreement. This automatic tool could allow professionals in the clinical setting to obtain an automatic quantitative and qualitative report of such events present in a voice sample, without having to manually analyze the whole EGG signal. In addition, it might provide the speech pathologist with more information that would complement the standard voice evaluation. It could also be a valuable tool in voice research. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Statistical analysis of lightning electric field measured under Malaysian condition

NASA Astrophysics Data System (ADS)

Salimi, Behnam; Mehranzamir, Kamyar; Abdul-Malek, Zulkurnain

2014-02-01

Lightning is an electrical discharge during thunderstorms that can be either within clouds (Inter-Cloud), or between clouds and ground (Cloud-Ground). The Lightning characteristics and their statistical information are the foundation for the design of lightning protection system as well as for the calculation of lightning radiated fields. Nowadays, there are various techniques to detect lightning signals and to determine various parameters produced by a lightning flash. Each technique provides its own claimed performances. In this paper, the characteristics of captured broadband electric fields generated by cloud-to-ground lightning discharges in South of Malaysia are analyzed. A total of 130 cloud-to-ground lightning flashes from 3 separate thunderstorm events (each event lasts for about 4-5 hours) were examined. Statistical analyses of the following signal parameters were presented: preliminary breakdown pulse train time duration, time interval between preliminary breakdowns and return stroke, multiplicity of stroke, and percentages of single stroke only. The BIL model is also introduced to characterize the lightning signature patterns. Observations on the statistical analyses show that about 79% of lightning signals fit well with the BIL model. The maximum and minimum of preliminary breakdown time duration of the observed lightning signals are 84 ms and 560 us, respectively. The findings of the statistical results show that 7.6% of the flashes were single stroke flashes, and the maximum number of strokes recorded was 14 multiple strokes per flash. A preliminary breakdown signature in more than 95% of the flashes can be identified.

Nonlinear unitary quantum collapse model with self-generated noise

NASA Astrophysics Data System (ADS)

Geszti, Tamás

2018-04-01

Collapse models including some external noise of unknown origin are routinely used to describe phenomena on the quantum-classical border; in particular, quantum measurement. Although containing nonlinear dynamics and thereby exposed to the possibility of superluminal signaling in individual events, such models are widely accepted on the basis of fully reproducing the non-signaling statistical predictions of quantum mechanics. Here we present a deterministic nonlinear model without any external noise, in which randomness—instead of being universally present—emerges in the measurement process, from deterministic irregular dynamics of the detectors. The treatment is based on a minimally nonlinear von Neumann equation for a Stern–Gerlach or Bell-type measuring setup, containing coordinate and momentum operators in a self-adjoint skew-symmetric, split scalar product structure over the configuration space. The microscopic states of the detectors act as a nonlocal set of hidden parameters, controlling individual outcomes. The model is shown to display pumping of weights between setup-defined basis states, with a single winner randomly selected and the rest collapsing to zero. Environmental decoherence has no role in the scenario. Through stochastic modelling, based on Pearle’s ‘gambler’s ruin’ scheme, outcome probabilities are shown to obey Born’s rule under a no-drift or ‘fair-game’ condition. This fully reproduces quantum statistical predictions, implying that the proposed non-linear deterministic model satisfies the non-signaling requirement. Our treatment is still vulnerable to hidden signaling in individual events, which remains to be handled by future research.

Hardware implementation of fuzzy Petri net as a controller.

PubMed

Gniewek, Lesław; Kluska, Jacek

2004-06-01

The paper presents a new approach to fuzzy Petri net (FPN) and its hardware implementation. The authors' motivation is as follows. Complex industrial processes can be often decomposed into many parallelly working subprocesses, which can, in turn, be modeled using Petri nets. If all the process variables (or events) are assumed to be two-valued signals, then it is possible to obtain a hardware or software control device, which works according to the algorithm described by conventional Petri net. However, the values of real signals are contained in some bounded interval and can be interpreted as events which are not only true or false, but rather true in some degree from the interval [0, 1]. Such a natural interpretation from multivalued logic (fuzzy logic) point of view, concerns sensor outputs, control signals, time expiration, etc. It leads to the idea of FPN as a controller, which one can rather simply obtain, and which would be able to process both analog, and binary signals. In the paper both graphical, and algebraic representations of the proposed FPN are given. The conditions under which transitions can be fired are described. The algebraic description of the net and a theorem which enables computation of new marking in the net, based on current marking, are formulated. Hardware implementation of the FPN, which uses fuzzy JK flip-flops and fuzzy gates, are proposed. An example illustrating usefulness of the proposed FPN for control algorithm description and its synthesis as a controller device for the concrete production process are presented.

MAP Kinase-Mediated Negative Regulation of Symbiotic Nodule Formation in Medicago truncatula.

PubMed

Ryu, Hojin; Laffont, Carole; Frugier, Florian; Hwang, Ildoo

2017-01-01

Mitogen-activated protein kinase (MAPK) signaling cascades play critical roles in various cellular events in plants, including stress responses, innate immunity, hormone signaling, and cell specificity. MAPK-mediated stress signaling is also known to negatively regulate nitrogen-fixing symbiotic interactions, but the molecular mechanism of the MAPK signaling cascades underlying the symbiotic nodule development remains largely unknown. We show that the MtMKK5-MtMPK3/6 signaling module negatively regulates the early symbiotic nodule formation, probably upstream of ERN1 (ERF Required for Nodulation 1) and NSP1 (Nod factor Signaling Pathway 1) in Medicago truncatula . The overexpression of MtMKK5 stimulated stress and defense signaling pathways but also reduced nodule formation in M. truncatula roots. Conversely, a MAPK specific inhibitor, U0126, enhanced nodule formation and the expression of an early nodulation marker gene, MtNIN . We found that MtMKK5 directly activates MtMPK3/6 by phosphorylating the TEY motif within the activation loop and that the MtMPK3/6 proteins physically interact with the early nodulation-related transcription factors ERN1 and NSP1. These data suggest that the stress signaling-mediated MtMKK5/MtMPK3/6 module suppresses symbiotic nodule development via the action of early nodulation transcription factors.

MAP Kinase-Mediated Negative Regulation of Symbiotic Nodule Formation in Medicago truncatula

PubMed Central

Ryu, Hojin; Laffont, Carole; Frugier, Florian; Hwang, Ildoo

2017-01-01

Mitogen-activated protein kinase (MAPK) signaling cascades play critical roles in various cellular events in plants, including stress responses, innate immunity, hormone signaling, and cell specificity. MAPK-mediated stress signaling is also known to negatively regulate nitrogen-fixing symbiotic interactions, but the molecular mechanism of the MAPK signaling cascades underlying the symbiotic nodule development remains largely unknown. We show that the MtMKK5-MtMPK3/6 signaling module negatively regulates the early symbiotic nodule formation, probably upstream of ERN1 (ERF Required for Nodulation 1) and NSP1 (Nod factor Signaling Pathway 1) in Medicago truncatula. The overexpression of MtMKK5 stimulated stress and defense signaling pathways but also reduced nodule formation in M. truncatula roots. Conversely, a MAPK specific inhibitor, U0126, enhanced nodule formation and the expression of an early nodulation marker gene, MtNIN. We found that MtMKK5 directly activates MtMPK3/6 by phosphorylating the TEY motif within the activation loop and that the MtMPK3/6 proteins physically interact with the early nodulation-related transcription factors ERN1 and NSP1. These data suggest that the stress signaling-mediated MtMKK5/MtMPK3/6 module suppresses symbiotic nodule development via the action of early nodulation transcription factors. PMID:28152300

Creep and slip: Seismic precursors to the Nuugaatsiaq landslide (Greenland)

NASA Astrophysics Data System (ADS)

Poli, Piero

2017-09-01

Precursory signals to material's failure are predicted by numerical models and observed in laboratory experiments or using field data. These precursory signals are a marker of slip acceleration on weak regions, such as crustal faults. Observation of these precursory signals of catastrophic natural events, such as earthquakes and landslides, is necessary for improving our knowledge about the physics of the nucleation process. Furthermore, observing such precursory signals may help to forecast these catastrophic events or reduce their hazard. I report here the observation of seismic precursors to the Nuugaatsiaq landslide in Greenland. Time evolution of the detected precursors implies that an aseismic slip event is taking place for hours before the landslide, with an exponential increase of slip velocity. Furthermore, time evolution of the precursory signals' amplitude sheds light on the evolution of the fault physics during the nucleation process.

Compact conscious animal positron emission tomography scanner

DOEpatents

Schyler, David J.; O'Connor, Paul; Woody, Craig; Junnarkar, Sachin Shrirang; Radeka, Veljko; Vaska, Paul; Pratte, Jean-Francois; Volkow, Nora

2006-10-24

A method of serially transferring annihilation information in a compact positron emission tomography (PET) scanner includes generating a time signal for an event, generating an address signal representing a detecting channel, generating a detector channel signal including the time and address signals, and generating a composite signal including the channel signal and similarly generated signals. The composite signal includes events from detectors in a block and is serially output. An apparatus that serially transfers annihilation information from a block includes time signal generators for detectors in a block and an address and channel signal generator. The PET scanner includes a ring tomograph that mounts onto a portion of an animal, which includes opposing block pairs. Each of the blocks in a block pair includes a scintillator layer, detection array, front-end array, and a serial encoder. The serial encoder includes time signal generators and an address signal and channel signal generator.

How Will Sea Ice Loss Affect the Greenland Ice Sheet? On the Puzzling Features of Greenland Ice-Core Isotopic Composition

NASA Technical Reports Server (NTRS)

Pausata, Francesco S. R.; Legrande, Allegra N.; Roberts, William H. G.

2016-01-01

The modern cryosphere, Earth's frozen water regime, is in fast transition. Greenland ice cores show how fast theses changes can be, presenting evidence of up to 15 C warming events over timescales of less than a decade. These events, called Dansgaard/Oeschger (D/O) events, are believed to be associated with rapid changes in Arctic sea ice, although the underlying mechanisms are still unclear. The modern demise of Arctic sea ice may, in turn, instigate abrupt changes on the Greenland Ice Sheet. The Arctic Sea Ice and Greenland Ice Sheet Sensitivity (Ice2Ice Chttps://ice2ice.b.uib.noD) initiative, sponsored by the European Research Council, seeks to quantify these past rapid changes to improve our understanding of what the future may hold for the Arctic. Twenty scientists gathered in Copenhagen as part of this initiative to discuss the most recent observational, technological, and model developments toward quantifying the mechanisms behind past climate changes in Greenland. Much of the discussion focused on the causes behind the changes in stable water isotopes recorded in ice cores. The participants discussed sources of variability for stable water isotopes and framed ways that new studies could improve understanding of modern climate. The participants also discussed how climate models could provide insights into the relative roles of local and nonlocal processes in affecting stable water isotopes within the Greenland Ice Sheet. Presentations of modeling results showed how a change in the source or seasonality of precipitation could occur not only between glacial and modern climates but also between abrupt events. Recent fieldwork campaigns illustrate an important role of stable isotopes in atmospheric vapor and diffusion in the final stable isotope signal in ice. Further, indications from recent fieldwork campaigns illustrate an important role of stable isotopes in atmospheric vapor and diffusion in the final stable isotope signal in ice. This feature complicates the quantitative interpretation of ice core signals but also makes the stable ice isotope signal a more robust regional indicator of climate, speakers noted. Meeting participants agreed that to further our understanding of these relationships, we need more process-focused field and laboratory campaigns.

[Molecular mechanisms of thymocyte differentiation].

PubMed

Kuklina, E M

2003-01-01

A review of the main molecular events occurring during differentiation of T-lymphocytes in the thymus: T-cell specialization of early intrathymic precursors, formation and expression of antigen receptor, formation of antigen recognizing cell repertoire, and alpha beta/gamma beta- and CD4/CD8-commitment. The mechanisms of glucocorticoid-induced apoptosis of thymocytes and its blockade during antigen-dependent activation are considered. A special attention is paid to the analysis of intracellular signals underlying the clonal selection of thymocytes.

Modulation of focal adhesion constituents and their down-stream events by EGF: On the cross-talk of integrins and growth factor receptors.

PubMed

Eberwein, Philipp; Laird, Dougal; Schulz, Simon; Reinhard, Thomas; Steinberg, Thorsten; Tomakidi, Pascal

2015-10-01

Within the concept of integrin growth factor receptor (GFR) cross-talk, little is known about the effects of GFRs on focal adhesions (FAs). Therefore, we tested the hypothesis whether EGF can modulate constituents of FAs and subsequent down-stream events. To this end, EGF-treated keratinocytes were subjected to combined fluorescence imaging and western blotting, to quantify expression and/or activation of molecules, involved in integrin GFR cross-talk, and receptor proximal and distal signaling events. Generally, EGF response revealed an amplified redistribution or activation of molecules under study, which will be explained in detail from the plasma membrane to the cell interior. In addition to significant activation of EGF receptor (EGFR) at tyrosine Tyr845, a remarkable redistribution was detectable for the focal adhesion constituents, integrin ß1 and ß3, and zyxin. Increased activation also applied to focal adhesion kinase (FAK) by phosphorylation at Tyr397, Tyr576, and Src at Tyr418, while total FAK remained unchanged. Risen activity was seen as well for the analyzed distal down-stream events, p190RhoGAP and MAP kinases p42/44. Intriguingly, Src-specific inhibitor Herbimycin A abrogated the entire EGF response except FAK Tyr397 phosphorylation, independent of EGF presence. Mechanistically, our results show that EGF modulates adhesion in a dual fashion, by firstly redistributing focal adhesion constituents to adhesion sites, but also by amplifying levels of activated RhoA antagonist p190RhoGAP, important for cell motility. Further, the findings suggest that the observed EGF response underlies an EGFR integrin cross-talk under recruitment of receptor proximal FAK and Src, and MAP kinase and p190RhoGAP as receptor distal events. Copyright © 2015 Elsevier B.V. All rights reserved.

Gene expression networks underlying ovarian development in wild largemouth bass (Micropterus salmoides).

PubMed

Martyniuk, Christopher J; Prucha, Melinda S; Doperalski, Nicholas J; Antczak, Philipp; Kroll, Kevin J; Falciani, Francesco; Barber, David S; Denslow, Nancy D

2013-01-01

Oocyte maturation in fish involves numerous cell signaling cascades that are activated or inhibited during specific stages of oocyte development. The objectives of this study were to characterize molecular pathways and temporal gene expression patterns throughout a complete breeding cycle in wild female largemouth bass to improve understanding of the molecular sequence of events underlying oocyte maturation. Transcriptomic analysis was performed on eight morphologically diverse stages of the ovary, including primary and secondary stages of oocyte growth, ovulation, and atresia. Ovary histology, plasma vitellogenin, 17β-estradiol, and testosterone were also measured to correlate with gene networks. Global expression patterns revealed dramatic differences across ovarian development, with 552 and 2070 genes being differentially expressed during both ovulation and atresia respectively. Gene set enrichment analysis (GSEA) revealed that early primary stages of oocyte growth involved increases in expression of genes involved in pathways of B-cell and T-cell receptor-mediated signaling cascades and fibronectin regulation. These pathways as well as pathways that included adrenergic receptor signaling, sphingolipid metabolism and natural killer cell activation were down-regulated at ovulation. At atresia, down-regulated pathways included gap junction and actin cytoskeleton regulation, gonadotrope and mast cell activation, and vasopressin receptor signaling and up-regulated pathways included oxidative phosphorylation and reactive oxygen species metabolism. Expression targets for luteinizing hormone signaling were low during vitellogenesis but increased 150% at ovulation. Other networks found to play a significant role in oocyte maturation included those with genes regulated by members of the TGF-beta superfamily (activins, inhibins, bone morphogenic protein 7 and growth differentiation factor 9), neuregulin 1, retinoid X receptor, and nerve growth factor family. This study offers novel insight into the gene networks underlying vitellogenesis, ovulation and atresia and generates new hypotheses about the cellular pathways regulating oocyte maturation.

Resilient filtering for time-varying stochastic coupling networks under the event-triggering scheduling

NASA Astrophysics Data System (ADS)

Wang, Fan; Liang, Jinling; Dobaie, Abdullah M.

2018-07-01

The resilient filtering problem is considered for a class of time-varying networks with stochastic coupling strengths. An event-triggered strategy is adopted to save the network resources by scheduling the signal transmission from the sensors to the filters based on certain prescribed rules. Moreover, the filter parameters to be designed are subject to gain perturbations. The primary aim of the addressed problem is to determine a resilient filter that ensures an acceptable filtering performance for the considered network with event-triggering scheduling. To handle such an issue, an upper bound on the estimation error variance is established for each node according to the stochastic analysis. Subsequently, the resilient filter is designed by locally minimizing the derived upper bound at each iteration. Moreover, rigorous analysis shows the monotonicity of the minimal upper bound regarding the triggering threshold. Finally, a simulation example is presented to show effectiveness of the established filter scheme.

Development of a GCR Event-based Risk Model

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Ponomarev, Artem L.; Plante, Ianik; Carra, Claudio; Kim, Myung-Hee

2009-01-01

A goal at NASA is to develop event-based systems biology models of space radiation risks that will replace the current dose-based empirical models. Complex and varied biochemical signaling processes transmit the initial DNA and oxidative damage from space radiation into cellular and tissue responses. Mis-repaired damage or aberrant signals can lead to genomic instability, persistent oxidative stress or inflammation, which are causative of cancer and CNS risks. Protective signaling through adaptive responses or cell repopulation is also possible. We are developing a computational simulation approach to galactic cosmic ray (GCR) effects that is based on biological events rather than average quantities such as dose, fluence, or dose equivalent. The goal of the GCR Event-based Risk Model (GERMcode) is to provide a simulation tool to describe and integrate physical and biological events into stochastic models of space radiation risks. We used the quantum multiple scattering model of heavy ion fragmentation (QMSFRG) and well known energy loss processes to develop a stochastic Monte-Carlo based model of GCR transport in spacecraft shielding and tissue. We validated the accuracy of the model by comparing to physical data from the NASA Space Radiation Laboratory (NSRL). Our simulation approach allows us to time-tag each GCR proton or heavy ion interaction in tissue including correlated secondary ions often of high multiplicity. Conventional space radiation risk assessment employs average quantities, and assumes linearity and additivity of responses over the complete range of GCR charge and energies. To investigate possible deviations from these assumptions, we studied several biological response pathway models of varying induction and relaxation times including the ATM, TGF -Smad, and WNT signaling pathways. We then considered small volumes of interacting cells and the time-dependent biophysical events that the GCR would produce within these tissue volumes to estimate how GCR event rates mapped to biological signaling induction and relaxation times. We considered several hypotheses related to signaling and cancer risk, and then performed simulations for conditions where aberrant or adaptive signaling would occur on long-duration space mission. Our results do not support the conventional assumptions of dose, linearity and additivity. A discussion on how event-based systems biology models, which focus on biological signaling as the mechanism to propagate damage or adaptation, can be further developed for cancer and CNS space radiation risk projections is given.

Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry.

PubMed

Feng, Xiaodong; Degese, Maria Sol; Iglesias-Bartolome, Ramiro; Vaque, Jose P; Molinolo, Alfredo A; Rodrigues, Murilo; Zaidi, M Raza; Ksander, Bruce R; Merlino, Glenn; Sodhi, Akrit; Chen, Qianming; Gutkind, J Silvio

2014-06-16

Mutually exclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding heterotrimeric Gαq family members, have been identified in ∼ 83% and ∼ 6% of uveal and skin melanomas, respectively. However, the molecular events underlying these GNAQ-driven malignancies are not yet defined, thus limiting the ability to develop cancer-targeted therapies. Here, we focused on the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway that controls organ size. We found that Gαq stimulates YAP through a Trio-Rho/Rac signaling circuitry promoting actin polymerization, independently of phospholipase Cβ and the canonical Hippo pathway. Furthermore, we show that Gαq promotes the YAP-dependent growth of uveal melanoma cells, thereby identifying YAP as a suitable therapeutic target in uveal melanoma, a GNAQ/GNA11-initiated human malignancy. Copyright © 2014 Elsevier Inc. All rights reserved.

Chemotaxis in Microfluidic Devices

NASA Astrophysics Data System (ADS)

Wyatt, Danica; Nadkarni, Sharvari; Song, Loling; Voeltz, Camilla; Bodenschatz, Eberhard

2004-03-01

Dictyostelium amoebae use chemical signaling to begin starvation-induced aggregation. Cells generate a complex and dynamic pattern of cyclic AMP that drives their migration toward a central point. While this phenomenon is unique to social amoebae, the signaling pathways of chemotaxis are similar in all eukaryotic cells. Dicty serves as a model organism for imaging these intracellular protein dynamics. To date, chemotaxis has been primarily studied in diffusion-generated gradients in chambers many orders of magnitude larger than a cell. To better quantify which aspects of a gradient trigger a response, we have designed a microfluidic channel that confines cells in an environment where spatiotemporal cAMP concentration can be precisely manipulated. We report results on an early event in the signaling cascade, the translocation of PH domain-containing proteins, which test current models of chemotaxis. This work was supported by the NSF Biocomplexity program and the Nanobiotechnology Center, an STC Program of the NSF under Agreement No. ECS-9876771.

Molecular mechanisms of gravity-dependent signaling in human melanocytic cells involve cyclic GMP

NASA Astrophysics Data System (ADS)

Ivanova, Krassimira; Lambers, Britta; Block, Ingrid; Bromeis, Birgit; Das, Pranab K.; Gerzer, Rupert

2005-08-01

Gravity alteration (micro- and hypergravity) is known to influence cell functions. As guanosine 3',5'-cyclic monophosphate (cGMP) is an important messenger in melanocyte signaling we have compared the regulation of cGMP levels in human melanocytes and melanoma cells with different metastatic potential under hypergravity conditions. We were able to demonstrate that long-term exposure to hypergravity stimulates cGMP efflux in cultured human melanocytes and non- metastatic melanoma cells, whereas highly metastatic melanoma cells appear to be insensitive to hypergravity, most probably, due to an up-regulated cGMP efflux at 1g. Here we report that these effects are associated with the expression of the multidrug resistance proteins 4 and 5 known to act as selective export pumps for amphiphilic anions like cGMP. Thus, an altered gravity vector may induce cGMP-dependent signaling events in melanocytic cells that could be important for malignant transformation.

Identification of needs and requirements defined by services subordinated to the Minister of the Interior and Administration in key technology and user interfaces to develop a concept of the Video Signals Integrator (VSI) system

NASA Astrophysics Data System (ADS)

Bukowiecka, Danuta; Tyburska, Agata; Struniawski, Jarosław; Jastrzebski, Pawel; Jewartowski, Blazej; Pozniak, Krzysztof; Kasprowicz, Grzegorz; Pastuszak, Grzegorz; Trochimiuk, Maciej; Abramowski, Andrzej; Gaska, Michal; Frasunek, Przemysław; Nalbach-Moszynska, Małgorzata; Brawata, Sebastian; Bubak, Iwona; Gloza, Małgorzata

2016-09-01

Preventing and eliminating the risks of terrorist attacks or natural disasters as well as an increase in the security of mass events and critical infrastructure requires the application of modern technologies. Therefore there is a proposal to construct a tool that integrates video signals transmitted by devices that are a part of video monitoring systems functioning in Poland. The article presents selected results of research conducted by the Police Academy in Szczytno under the implemented project for national defense and security on "Video Signals Integrator" Acronym - VSI. Project Leader: Warsaw University of Technology. The consortium: Police Academy in Szczytno, Atende Software Ltd., VORTEX Ltd. No. DOBBio7/ 01/02/2015 funded by the National Centre for Research and Development.

Spatiotemporal antagonism in mesenchymal-epithelial signaling in sweat versus hair fate decision.

PubMed

Lu, Catherine P; Polak, Lisa; Keyes, Brice E; Fuchs, Elaine

2016-12-23

The gain of eccrine sweat glands in hairy body skin has empowered humans to run marathons and tolerate temperature extremes. Epithelial-mesenchymal cross-talk is integral to the diverse patterning of skin appendages, but the molecular events underlying their specification remain largely unknown. Using genome-wide analyses and functional studies, we show that sweat glands are specified by mesenchymal-derived bone morphogenetic proteins (BMPs) and fibroblast growth factors that signal to epithelial buds and suppress epithelial-derived sonic hedgehog (SHH) production. Conversely, hair follicles are specified when mesenchymal BMP signaling is blocked, permitting SHH production. Fate determination is confined to a critical developmental window and is regionally specified in mice. In contrast, a shift from hair to gland fates is achieved in humans when a spike in BMP silences SHH during the final embryonic wave(s) of bud morphogenesis. Copyright © 2016, American Association for the Advancement of Science.

Ionic signaling in plant gravity and touch responses

NASA Technical Reports Server (NTRS)

Massa, Gioia D.; Fasano, Jeremiah M.; Gilroy, Simon

2003-01-01

Plant roots are optimized to exploit resources from the soil and as each root explores this environment it will encounter a range of biotic and abiotic stimuli to which it must respond. Therefore, each root must possess a sensory array capable of monitoring and integrating these diverse stimuli to direct the appropriate growth response. Touch and gravity represent two of the biophysical stimuli that plants must integrate. As sensing both of these signals requires mechano-transduction of biophysical forces to biochemical signaling events, it is likely that they share signal transduction elements. These common signaling components may allow for cross-talk and so integration of thigmotropic and gravitropic responses. Indeed, signal transduction events in both plant touch and gravity sensing are thought to include Ca(2+)- and pH-dependent events. Additionally, it seems clear that the systems responsible for root touch and gravity response interact to generate an integrated growth response. Thus, primary and lateral roots of Arabidopsis respond to mechanical stimuli by eliciting tropic growth that is likely part of a growth strategy employed by the root to circumvent obstacles in the soil. Also, the mechano-signaling induced by encountering an obstacle apparently down-regulates the graviperception machinery to allow this kind of avoidance response. The challenge for future research will be to define how the cellular signaling events in the root cap facilitate this signal integration and growth regulation. In addition, whether other stimuli are likewise integrated with the graviresponse via signal transduction system cross-talk is an important question that remains to be answered.

A novel method to accurately locate and count large numbers of steps by photobleaching.

PubMed

Tsekouras, Konstantinos; Custer, Thomas C; Jashnsaz, Hossein; Walter, Nils G; Pressé, Steve

2016-11-07

Photobleaching event counting is a single-molecule fluorescence technique that is increasingly being used to determine the stoichiometry of protein and RNA complexes composed of many subunits in vivo as well as in vitro. By tagging protein or RNA subunits with fluorophores, activating them, and subsequently observing as the fluorophores photobleach, one obtains information on the number of subunits in a complex. The noise properties in a photobleaching time trace depend on the number of active fluorescent subunits. Thus, as fluorophores stochastically photobleach, noise properties of the time trace change stochastically, and these varying noise properties have created a challenge in identifying photobleaching steps in a time trace. Although photobleaching steps are often detected by eye, this method only works for high individual fluorophore emission signal-to-noise ratios and small numbers of fluorophores. With filtering methods or currently available algorithms, it is possible to reliably identify photobleaching steps for up to 20-30 fluorophores and signal-to-noise ratios down to ∼1. Here we present a new Bayesian method of counting steps in photobleaching time traces that takes into account stochastic noise variation in addition to complications such as overlapping photobleaching events that may arise from fluorophore interactions, as well as on-off blinking. Our method is capable of detecting ≥50 photobleaching steps even for signal-to-noise ratios as low as 0.1, can find up to ≥500 steps for more favorable noise profiles, and is computationally inexpensive. © 2016 Tsekouras et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

A method for detecting and locating geophysical events using groups of arrays

NASA Astrophysics Data System (ADS)

de Groot-Hedlin, Catherine D.; Hedlin, Michael A. H.

2015-11-01

We have developed a novel method to detect and locate geophysical events that makes use of any sufficiently dense sensor network. This method is demonstrated using acoustic sensor data collected in 2013 at the USArray Transportable Array (TA). The algorithm applies Delaunay triangulation to divide the sensor network into a mesh of three-element arrays, called triads. Because infrasound waveforms are incoherent between the sensors within each triad, the data are transformed into envelopes, which are cross-correlated to find signals that satisfy a consistency criterion. The propagation azimuth, phase velocity and signal arrival time are computed for each signal. Triads with signals that are consistent with a single source are bundled as an event group. The ensemble of arrival times and azimuths of detected signals within each group are used to locate a common source in space and time. A total of 513 infrasonic stations that were active for part or all of 2013 were divided into over 2000 triads. Low (0.5-2 Hz) and high (2-8 Hz) catalogues of infrasonic events were created for the eastern USA. The low-frequency catalogue includes over 900 events and reveals several highly active source areas on land that correspond with coal mining regions. The high-frequency catalogue includes over 2000 events, with most occurring offshore. Although their cause is not certain, most events are clearly anthropogenic as almost all occur during regular working hours each week. The regions to which the TA is most sensitive vary seasonally, with the direction of reception dependent on the direction of zonal winds. The catalogue has also revealed large acoustic events that may provide useful insight into the nature of long-range infrasound propagation in the atmosphere.

Possibility of Earthquake-prediction by analyzing VLF signals

NASA Astrophysics Data System (ADS)

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

2016-07-01

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

Annotation and prediction of stress and workload from physiological and inertial signals.

PubMed

Ghosh, Arindam; Danieli, Morena; Riccardi, Giuseppe

2015-08-01

Continuous daily stress and high workload can have negative effects on individuals' physical and mental well-being. It has been shown that physiological signals may support the prediction of stress and workload. However, previous research is limited by the low diversity of signals concurring to such predictive tasks and controlled experimental design. In this paper we present 1) a pipeline for continuous and real-life acquisition of physiological and inertial signals 2) a mobile agent application for on-the-go event annotation and 3) an end-to-end signal processing and classification system for stress and workload from diverse signal streams. We study physiological signals such as Galvanic Skin Response (GSR), Skin Temperature (ST), Inter Beat Interval (IBI) and Blood Volume Pulse (BVP) collected using a non-invasive wearable device; and inertial signals collected from accelerometer and gyroscope sensors. We combine them with subjects' inputs (e.g. event tagging) acquired using the agent application, and their emotion regulation scores. In our experiments we explore signal combination and selection techniques for stress and workload prediction from subjects whose signals have been recorded continuously during their daily life. The end-to-end classification system is described for feature extraction, signal artifact removal, and classification. We show that a combination of physiological, inertial and user event signals provides accurate prediction of stress for real-life users and signals.

Detection of cough signals in continuous audio recordings using hidden Markov models.

PubMed

Matos, Sergio; Birring, Surinder S; Pavord, Ian D; Evans, David H

2006-06-01

Cough is a common symptom of many respiratory diseases. The evaluation of its intensity and frequency of occurrence could provide valuable clinical information in the assessment of patients with chronic cough. In this paper we propose the use of hidden Markov models (HMMs) to automatically detect cough sounds from continuous ambulatory recordings. The recording system consists of a digital sound recorder and a microphone attached to the patient's chest. The recognition algorithm follows a keyword-spotting approach, with cough sounds representing the keywords. It was trained on 821 min selected from 10 ambulatory recordings, including 2473 manually labeled cough events, and tested on a database of nine recordings from separate patients with a total recording time of 3060 min and comprising 2155 cough events. The average detection rate was 82% at a false alarm rate of seven events/h, when considering only events above an energy threshold relative to each recording's average energy. These results suggest that HMMs can be applied to the detection of cough sounds from ambulatory patients. A postprocessing stage to perform a more detailed analysis on the detected events is under development, and could allow the rejection of some of the incorrectly detected events.

TCR Signal Strength Alters T–DC Activation and Interaction Times and Directs the Outcome of Differentiation

PubMed Central

van Panhuys, Nicholas

2016-01-01

The ability of CD4+ T cells to differentiate into effector subsets underpins their ability to shape the immune response and mediate host protection. During T cell receptor-induced activation of CD4+ T cells, both the quality and quantity of specific activatory peptide/MHC ligands have been shown to control the polarization of naive CD4+ T cells in addition to co-stimulatory and cytokine-based signals. Recently, advances in two-­photon microscopy and tetramer-based cell tracking methods have allowed investigators to greatly extend the study of the role of TCR signaling in effector differentiation under in vivo conditions. In this review, we consider data from recent in vivo studies analyzing the role of TCR signal strength in controlling the outcome of CD4+ T cell differentiation and discuss the role of TCR in controlling the critical nature of CD4+ T cell interactions with dendritic cells during activation. We further propose a model whereby TCR signal strength controls the temporal aspects of T–DC interactions and the implications for this in mediating the downstream signaling events, which influence the transcriptional and epigenetic regulation of effector differentiation. PMID:26834747

The role of the JAK/STAT signal pathway in rheumatoid arthritis

PubMed Central

Malemud, Charles J.

2018-01-01

Proinflammatory cytokine activation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal transduction pathway is a critical event in the pathogenesis and progression of rheumatoid arthritis. Under normal conditions, JAK/STAT signaling reflects the influence of negative regulators of JAK/STAT, exemplified by the suppressor of cytokine signaling and protein inhibitor of activated STAT. However, in rheumatoid arthritis (RA) both of these regulators are dysfunctional. Thus, continuous activation of JAK/STAT signaling in RA synovial joints results in the elevated level of matrix metalloproteinase gene expression, increased frequency of apoptotic chondrocytes and most prominently ‘apoptosis resistance’ in the inflamed synovial tissue. Tofacitinib, a JAK small molecule inhibitor, with selectivity for JAK2/JAK3 was approved by the United States Food and Drug Administration (US FDA) for the therapy of RA. Importantly, tofacitinib has demonstrated significant clinical efficacy for RA in the post-US FDA-approval surveillance period. Of note, the success of tofacitinib has spurred the development of JAK1, JAK2 and other JAK3-selective small molecule inhibitors, some of which have also entered the clinical setting, whereas other JAK inhibitors are currently being evaluated in RA clinical trials. PMID:29942363

DETECT: a MATLAB toolbox for event detection and identification in time series, with applications to artifact detection in EEG signals.

PubMed

Lawhern, Vernon; Hairston, W David; Robbins, Kay

2013-01-01

Recent advances in sensor and recording technology have allowed scientists to acquire very large time-series datasets. Researchers often analyze these datasets in the context of events, which are intervals of time where the properties of the signal change relative to a baseline signal. We have developed DETECT, a MATLAB toolbox for detecting event time intervals in long, multi-channel time series. Our primary goal is to produce a toolbox that is simple for researchers to use, allowing them to quickly train a model on multiple classes of events, assess the accuracy of the model, and determine how closely the results agree with their own manual identification of events without requiring extensive programming knowledge or machine learning experience. As an illustration, we discuss application of the DETECT toolbox for detecting signal artifacts found in continuous multi-channel EEG recordings and show the functionality of the tools found in the toolbox. We also discuss the application of DETECT for identifying irregular heartbeat waveforms found in electrocardiogram (ECG) data as an additional illustration.

DETECT: A MATLAB Toolbox for Event Detection and Identification in Time Series, with Applications to Artifact Detection in EEG Signals

PubMed Central

Lawhern, Vernon; Hairston, W. David; Robbins, Kay

2013-01-01

Recent advances in sensor and recording technology have allowed scientists to acquire very large time-series datasets. Researchers often analyze these datasets in the context of events, which are intervals of time where the properties of the signal change relative to a baseline signal. We have developed DETECT, a MATLAB toolbox for detecting event time intervals in long, multi-channel time series. Our primary goal is to produce a toolbox that is simple for researchers to use, allowing them to quickly train a model on multiple classes of events, assess the accuracy of the model, and determine how closely the results agree with their own manual identification of events without requiring extensive programming knowledge or machine learning experience. As an illustration, we discuss application of the DETECT toolbox for detecting signal artifacts found in continuous multi-channel EEG recordings and show the functionality of the tools found in the toolbox. We also discuss the application of DETECT for identifying irregular heartbeat waveforms found in electrocardiogram (ECG) data as an additional illustration. PMID:23638169

Inelastic Single Pion Signal Study in T2K νe Appearance using Modified Decay Electron Cut

NASA Astrophysics Data System (ADS)

Iwamoto, Konosuke; T2K Collaboration

2015-04-01

The T2K long-baseline neutrino experiment uses sophisticated selection criteria to identify the neutrino oscillation signals among the events reconstructed in the Super-Kamiokande (SK) detector for νe and νμ appearance and disappearance analyses. In current analyses, charged-current quasi-elastic (CCQE) events are used as the signal reaction in the SK detector because the energy can be precisely reconstructed. This talk presents an approach to increase the statistics of the oscillation analysis by including non-CCQE events with one Michel electron and reconstruct them as the inelastic single pion productions. The increase in statistics, backgrounds to this new process and energy reconstruction implications will be presented with this increased event sample.

Studying the Romanian Shelf benthic community in EU FP7 HYPOX Project: ecosystem recovery trends vs. fish kill events

NASA Astrophysics Data System (ADS)

Gomoiu, M.-T.; Begun, T.; Caraus, I.; Muresan, M.; Oaie, G.; Opreanu, P.; Secrieru, D.; Teaca, A.; Vasiliu, D.

2012-04-01

The main objective of the study was the assessment of marine ecosystem recovery post heavy eutrophication/pollution of 1970-1995, including hypoxia, under the conditions of increasing climate changes in the NW Black Sea sector. The paper aims are: 1. the understanding of the present ecological state of the ecosystem under the Danube River influence, 2. the highlight of emergent events and evidences of algal blooms and mass mortalities, 3. the knowledge of firm signs of recovery and 4. the establishing the certainties and uncertainties in benthic succession. The authors present, on the basis of four main series of data (May 2009, May and September 2010 and April 2011) from 110 stations along three transects (SE-Sf. Gheorghe, in front of the Danube Delta, SE-Constanta and E-Mangalia) and in the sheltered area of Portita, the preliminary conclusions regarding the state variables of water masses, surface bottom sediments and biological communities of phytoplankton, zooplankton and benthos. NW Black Sea ecosystem is under continuum complex stress of the Danube River discharges and human activities; these basic conditions generate oscillations in its structure and dynamics, being the origin of horizontal and vertical variability of all state parameters. Nowadays, under the climate change conditions, the situation has become more complex. Compiling the existing and newly collected data the paper describes the regime shifts taking place in ecosystems in the last decades. Discussions focus on the results of the analyses obtained from the following samples: 10 sediments cores; 417 seawater samples; 336 phytoplankton samples; 214 zooplankton samples; 110 macrobenthos samples and 130 meiobenthos samples. The paper brings new data on the following major aspects concerning the ecological state in NW Black Sea in 2009-2011. - The pressure of the Danube River chemical discharges has decreased obviously, but water blooming events still occur, hypoxia is still present from time to time and there are mass mortalities of fish and other benthic organisms; the mass mortality of fishes in July 2010 is discussed in the paper. - The authors consider signals of ecological recovery as being fragile and few, among them being mentioned the reappearance of species absent in the samples collected in the period 1970 -1990/95, which is a promising signal. Recurrence of species extinct in the last 20-30 years may be considered a good signal, but there are also questions which are discussed in the paper too. - Recovery signs should be considered cautiously and the uncertainties could be solved only in a longer time by increasing the scientific efforts at the level of the whole basin. The occurrence of explosive events with a random character, sudden warming and cooling of water, sudden episodic freshening of water, large variations in gradients of state parameters, blooming, emergence of hypoxia, mass mortalities of fish and benthic organisms, raise many question marks.

GRAVITATIONAL MICROLENSING EVENTS AS A TARGET FOR THE SETI PROJECT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rahvar, Sohrab, E-mail: rahvar@sharif.edu

2016-09-01

The detection of signals from a possible extrasolar technological civilization is one of the most challenging efforts of science. In this work, we propose using natural telescopes made of single or binary gravitational lensing systems to magnify leakage of electromagnetic signals from a remote planet that harbors Extraterrestrial Intelligent (ETI) technology. Currently, gravitational microlensing surveys are monitoring a large area of the Galactic bulge to search for microlensing events, finding more than 2000 events per year. These lenses are capable of playing the role of natural telescopes, and, in some instances, they can magnify radio band signals from planets orbitingmore » around the source stars in gravitational microlensing systems. Assuming that the frequency of electromagnetic waves used for telecommunication in ETIs is similar to ours, we propose follow-up observation of microlensing events with radio telescopes such as the Square Kilometre Array (SKA), the Low Frequency Demonstrators, and the Mileura Wide-Field Array. Amplifying signals from the leakage of broadcasting by an Earth-like civilization will allow us to detect them as far as the center of the Milky Way galaxy. Our analysis shows that in binary microlensing systems, the probability of amplification of signals from ETIs is more than that in single microlensing events. Finally, we propose the use of the target of opportunity mode for follow-up observations of binary microlensing events with SKA as a new observational program for searching ETIs. Using optimistic values for the factors of the Drake equation provides detection of about one event per year.« less

Test apparatus to monitor time-domain signals from semiconductor-detector pixel arrays

NASA Astrophysics Data System (ADS)

Haston, Kyle; Barber, H. Bradford; Furenlid, Lars R.; Salçin, Esen; Bora, Vaibhav

2011-10-01

Pixellated semiconductor detectors, such as CdZnTe, CdTe, or TlBr, are used for gamma-ray imaging in medicine and astronomy. Data analysis for these detectors typically estimates the position (x, y, z) and energy (E) of each interacting gamma ray from a set of detector signals {Si} corresponding to completed charge transport on the hit pixel and any of its neighbors that take part in charge sharing, plus the cathode. However, it is clear from an analysis of signal induction, that there are transient signal on all pixel electrodes during the charge transport and, when there is charge trapping, small negative residual signals on all electrodes. If we wish to optimally obtain the event parameters, we should take all these signals into account. We wish to estimate x,y,z and E from the set of all electrode signals, {Si(t)}, including time dependence, using maximum-likelihood techniques[1]. To do this, we need to determine the probability of the electrode signals, given the event parameters {x, y, z, E}, i.e. Pr( {Si(t)} | {x, y, z, E} ). Thus we need to map the detector response of all pixels, {Si(t)}, for a large number of events with known x,y,z and E.In this paper we demonstrate the existence of the transient signals and residual signals and determine their magnitudes. They are typically 50-100 times smaller than the hit-pixel signals. We then describe development of an apparatus to measure the response of a 16-pixel semiconductor detector and show some preliminary results. We also discuss techniques for measuring the event parameters for individual gamma-ray interactions, a requirement for determining Pr( {Si(t)} | {x, y, z, E}).

Event-Related Oscillations in Alcoholism Research: A Review

PubMed Central

Pandey, Ashwini K; Kamarajan, Chella; Rangaswamy, Madhavi; Porjesz, Bernice

2013-01-01

Alcohol dependence is characterized as a multi-factorial disorder caused by a complex interaction between genetic and environmental liabilities across development. A variety of neurocognitive deficits/dysfunctions involving impairments in different brain regions and/or neural circuitries have been associated with chronic alcoholism, as well as with a predisposition to develop alcoholism. Several neurobiological and neurobehavioral approaches and methods of analyses have been used to understand the nature of these neurocognitive impairments/deficits in alcoholism. In the present review, we have examined relatively novel methods of analyses of the brain signals that are collectively referred to as event-related oscillations (EROs) and show promise to further our understanding of human brain dynamics while performing various tasks. These new measures of dynamic brain processes have exquisite temporal resolution and allow the study of neural networks underlying responses to sensory and cognitive events, thus providing a closer link to the physiology underlying them. Here, we have reviewed EROs in the study of alcoholism, their usefulness in understanding dynamical brain functions/dysfunctions associated with alcoholism as well as their utility as effective endophenotypes to identify and understand genes associated with both brain oscillations and alcoholism. PMID:24273686

NMDA receptor activation upstream of methyl farnesoate signaling for short day-induced male offspring production in the water flea, Daphnia pulex.

PubMed

Toyota, Kenji; Miyakawa, Hitoshi; Yamaguchi, Katsushi; Shigenobu, Shuji; Ogino, Yukiko; Tatarazako, Norihisa; Miyagawa, Shinichi; Iguchi, Taisen

2015-03-14

The cladoceran crustacean Daphnia pulex produces female offspring by parthenogenesis under favorable conditions, but in response to various unfavorable external stimuli, it produces male offspring (environmental sex determination: ESD). We recently established an innovative system for ESD studies using D. pulex WTN6 strain, in which the sex of the offspring can be controlled simply by changes in the photoperiod: the long-day and short-day conditions can induce female and male offspring, respectively. Taking advantage of this system, we demonstrated that de novo methyl farnesoate (MF) synthesis is necessary for male offspring production. These results indicate the key role of innate MF signaling as a conductor between external environmental stimuli and the endogenous male developmental pathway. Despite these findings, the molecular mechanisms underlying up- and downstream signaling of MF have not yet been well elucidated in D. pulex. To elucidate up- and downstream events of MF signaling during sex determination processes, we compared the transcriptomes of daphnids reared under the long-day (female) condition with short-day (male) and MF-treated (male) conditions. We found that genes involved in ionotropic glutamate receptors, known to mediate the vast majority of excitatory neurotransmitting processes in various organisms, were significantly activated in daphnids by the short-day condition but not by MF treatment. Administration of specific agonists and antagonists, especially for the N-methyl-D-aspartic acid (NMDA) receptor, strongly increased or decreased, respectively, the proportion of male-producing mothers. Moreover, we also identified genes responsible for male production (e.g., protein kinase C pathway-related genes). Such genes were generally shared between the short-day reared and MF-treated daphnids. We identified several candidate genes regulating ESD which strongly suggests that these genes may be essential factors for male offspring production as an upstream regulator of MF signaling in D. pulex. This study provides new insight into the fundamental mechanisms underlying how living organisms alter their phenotypes in response to various external environments.

Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine.

PubMed

Berry, Richard B; Budhiraja, Rohit; Gottlieb, Daniel J; Gozal, David; Iber, Conrad; Kapur, Vishesh K; Marcus, Carole L; Mehra, Reena; Parthasarathy, Sairam; Quan, Stuart F; Redline, Susan; Strohl, Kingman P; Davidson Ward, Sally L; Tangredi, Michelle M

2012-10-15

The American Academy of Sleep Medicine (AASM) Sleep Apnea Definitions Task Force reviewed the current rules for scoring respiratory events in the 2007 AASM Manual for the Scoring and Sleep and Associated Events to determine if revision was indicated. The goals of the task force were (1) to clarify and simplify the current scoring rules, (2) to review evidence for new monitoring technologies relevant to the scoring rules, and (3) to strive for greater concordance between adult and pediatric rules. The task force reviewed the evidence cited by the AASM systematic review of the reliability and validity of scoring respiratory events published in 2007 and relevant studies that have appeared in the literature since that publication. Given the limitations of the published evidence, a consensus process was used to formulate the majority of the task force recommendations concerning revisions.The task force made recommendations concerning recommended and alternative sensors for the detection of apnea and hypopnea to be used during diagnostic and positive airway pressure (PAP) titration polysomnography. An alternative sensor is used if the recommended sensor fails or the signal is inaccurate. The PAP device flow signal is the recommended sensor for the detection of apnea, hypopnea, and respiratory effort related arousals (RERAs) during PAP titration studies. Appropriate filter settings for recording (display) of the nasal pressure signal to facilitate visualization of inspiratory flattening are also specified. The respiratory inductance plethysmography (RIP) signals to be used as alternative sensors for apnea and hypopnea detection are specified. The task force reached consensus on use of the same sensors for adult and pediatric patients except for the following: (1) the end-tidal PCO(2) signal can be used as an alternative sensor for apnea detection in children only, and (2) polyvinylidene fluoride (PVDF) belts can be used to monitor respiratory effort (thoracoabdominal belts) and as an alternative sensor for detection of apnea and hypopnea (PVDFsum) only in adults.The task force recommends the following changes to the 2007 respiratory scoring rules. Apnea in adults is scored when there is a drop in the peak signal excursion by ≥ 90% of pre-event baseline using an oronasal thermal sensor (diagnostic study), PAP device flow (titration study), or an alternative apnea sensor, for ≥ 10 seconds. Hypopnea in adults is scored when the peak signal excursions drop by ≥ 30% of pre-event baseline using nasal pressure (diagnostic study), PAP device flow (titration study), or an alternative sensor, for ≥ 10 seconds in association with either ≥ 3% arterial oxygen desaturation or an arousal. Scoring a hypopnea as either obstructive or central is now listed as optional, and the recommended scoring rules are presented. In children an apnea is scored when peak signal excursions drop by ≥ 90% of pre-event baseline using an oronasal thermal sensor (diagnostic study), PAP device flow (titration study), or an alternative sensor; and the event meets duration and respiratory effort criteria for an obstructive, mixed, or central apnea. A central apnea is scored in children when the event meets criteria for an apnea, there is an absence of inspiratory effort throughout the event, and at least one of the following is met: (1) the event is ≥ 20 seconds in duration, (2) the event is associated with an arousal or ≥ 3% oxygen desaturation, (3) (infants under 1 year of age only) the event is associated with a decrease in heart rate to less than 50 beats per minute for at least 5 seconds or less than 60 beats per minute for 15 seconds. A hypopnea is scored in children when the peak signal excursions drop is ≥ 30% of pre-event baseline using nasal pressure (diagnostic study), PAP device flow (titration study), or an alternative sensor, for ≥ the duration of 2 breaths in association with either ≥ 3% oxygen desaturation or an arousal. In children and adults, surrogates of the arterial PCO(2) are the end-tidal PCO(2) or transcutaneous PCO(2) (diagnostic study) or transcutaneous PCO(2) (titration study). For adults, sleep hypoventilation is scored when the arterial PCO(2) (or surrogate) is > 55 mm Hg for ≥ 10 minutes or there is an increase in the arterial PCO(2) (or surrogate) ≥ 10 mm Hg (in comparison to an awake supine value) to a value exceeding 50 mm Hg for ≥ 10 minutes. For pediatric patients hypoventilation is scored when the arterial PCO(2) (or surrogate) is > 50 mm Hg for > 25% of total sleep time. In adults Cheyne-Stokes breathing is scored when both of the following are met: (1) there are episodes of ≥ 3 consecutive central apneas and/or central hypopneas separated by a crescendo and decrescendo change in breathing amplitude with a cycle length of at least 40 seconds (typically 45 to 90 seconds), and (2) there are five or more central apneas and/or central hypopneas per hour associated with the crescendo/decrescendo breathing pattern recorded over a minimum of 2 hours of monitoring.

Detection of Sleep Disordered Breathing and Its Central/Obstructive Character Using Nasal Cannula and Finger Pulse Oximeter

PubMed Central

Sommermeyer, Dirk; Zou, Ding; Grote, Ludger; Hedner, Jan

2012-01-01

Study Objective: To assess the accuracy of novel algorithms using an oximeter-based finger plethysmographic signal in combination with a nasal cannula for the detection and differentiation of central and obstructive apneas. The validity of single pulse oximetry to detect respiratory disturbance events was also studied. Methods: Patients recruited from four sleep laboratories underwent an ambulatory overnight cardiorespiratory polygraphy recording. The nasal flow and photoplethysmographic signals of the recording were analyzed by automated algorithms. The apnea hypopnea index (AHIauto) was calculated using both signals, and a respiratory disturbance index (RDIauto) was calculated from photoplethysmography alone. Apnea events were classified into obstructive and central types using the oximeter derived pulse wave signal and compared with manual scoring. Results: Sixty-six subjects (42 males, age 54 ± 14 yrs, body mass index 28.5 ± 5.9 kg/m2) were included in the analysis. AHImanual (19.4 ± 18.5 events/h) correlated highly significantly with AHIauto (19.9 ± 16.5 events/h) and RDIauto (20.4 ± 17.2 events/h); the correlation coefficients were r = 0.94 and 0.95, respectively (p < 0.001) with a mean difference of −0.5 ± 6.6 and −1.0 ± 6.1 events/h. The automatic analysis of AHIauto and RDIauto detected sleep apnea (cutoff AHImanual ≥ 15 events/h) with a sensitivity/specificity of 0.90/0.97 and 0.86/0.94, respectively. The automated obstructive/central apnea indices correlated closely with manually scoring (r = 0.87 and 0.95, p < 0.001) with mean difference of −4.3 ± 7.9 and 0.3 ± 1.5 events/h, respectively. Conclusions: Automatic analysis based on routine pulse oximetry alone may be used to detect sleep disordered breathing with accuracy. In addition, the combination of photoplethysmographic signals with a nasal flow signal provides an accurate distinction between obstructive and central apneic events during sleep. Citation: Sommermeyer D; Zou D; Grote L; Hedner J. Detection of sleep disordered breathing and its central/obstructive character using nasal cannula and finger pulse oximeter. J Clin Sleep Med 2012;8(5):527-533. PMID:23066364

Abundant spontaneous VLFE activities in Cascadia during ETS and inter-ETS time periods

NASA Astrophysics Data System (ADS)

Ghosh, A.; Hutchison, A. A.; Hawthorne, J.

2017-12-01

Very low frequency earthquakes (VLFEs) are discrete seismic events associated with episodic tremor and slip (ETS) events. They are rich in 20-50s energy and depleted in higher frequencies compared to regular local earthquakes of similar magnitudes. VLFEs can be as large as Mw 4.0, and potentially release much more seismic moment than the tremor/LFE activities, making them a critical event determining stress evolution during slow earthquakes [Ghosh et al., 2015]. Their underlying physics and relationship with tremor/LFE, however, are still unclear. In Cascadia, the majority of the VLFEs found so far are clustered near the areas of high geodetic slip during ETS events [Ghosh et al., 2015; Hutchison and Ghosh, 2016]. Interestingly, we found VLFE activity has its own dynamics and can occur independent of tremor/LFE activity. For example, during the 2014 ETS event in northern Cascadia, VLFEs are found to be asynchronous with tremor activity, both in space and time [Hutchison and Ghosh, 2016]. We use a matched filter technique to detect thousands of VLFEs over an ETS-cycle, and perhaps more interestingly, even between ETS events. VLFE activities peak during ETS events, but significant VLFE activity is detected during the inter-ETS time period. Analyses of strainmeter data near the VLFE locations suggest statistically significant strain rate increases during VLFE time periods compared to the background. We suggest that VLFE is a distinct type of seismic radiation different from tremor/LFE, and can operate independently from tremor activities. This is in contrast to a model suggesting that VLFE signals may be a result of many LFE signals arriving at seismic stations in a short time period [Gomberg et al., 2016]. We are making a consistent catalog of VLFE in Cascadia for longer time period. Systematic study of VLFEs is going to provide new insights into the mechanism of slow earthquakes and its relationship with tremor/LFE and slow slip.

Seismic data acquisition at the FACT site for the CASPAR project.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, Kyle R.; Chael, Eric Paul; Hart, Darren M.

Since May 2010, we have been recording continuous seismic data at Sandia's FACT site. The collected signals provide us with a realistic archive for testing algorithms under development for local monitoring of explosive testing. Numerous small explosive tests are routinely conducted around Kirtland AFB by different organizations. Our goal is to identify effective methods for distinguishing these events from normal daily activity on and near the base, such as vehicles, aircraft, and storms. In this report, we describe the recording system, and present some observations of the varying ambient noise conditions at FACT. We present examples of various common, non-explosive,more » sources. Next we show signals from several small explosions, and discuss their characteristic features.« less

TNF-induced necroptosis requires the plasma membrane localization of the MLKL protein | Center for Cancer Research

Cancer.gov

The cell signaling protein tumor necrosis factor (TNF), produced by white blood cells, promotes inflammation and immunity processes such as fever and is involved in tumorigenesis and apoptosis (programmed cell death). However, dysregulation of TNF can also lead to another form of programmed cell death called necroptosis, which is characterized by a rise in intracellular Ca2+, generation of reactive oxygen species (ROS), intracellular acidity, depletion of ATP, and, eventually, plasma membrane rupture. TNF-induced necroptosis has been associated with a wide variety of diseases including neurodegenerative diseases, major depression, rheumatoid arthritis, and cancer. Whereas the signaling mechanisms underlying TNF-induced apoptosis have largely been determined, the events precipitating in TNF-initiated necroptosis are still unknown.

Solid xenon radiation detectors

NASA Astrophysics Data System (ADS)

Dolinski, Michelle J.

2014-03-01

Cryogenic liquid xenon detectors have become a popular technology in the search for rare events, such as dark matter interactions and neutrinoless double beta decay. The power of the liquid xenon detector technology is in the combination of the ionization and scintillation signals, resulting in particle discrimination and improved energy resolution over the ionization-only signal. The improved energy resolution results from a unique anti-correlation phenomenon that has not been described from first principles. Solid xenon bolometers, under development at Drexel University, are expected to have excellent counting statistics in the phonon channel, with energy resolution of 0.1% or better. This additional energy channel may offer the final piece of the puzzle in understanding liquid xenon detector energy response. Supported by a grant from the Charles E. Kaufman Foundation.

Involvement of Hormone- and ROS-Signaling Pathways in the Beneficial Action of Humic Substances on Plants Growing under Normal and Stressing Conditions

PubMed Central

García, Andrés Calderín; Olaetxea, Maite; Santos, Leandro Azevedo; Mora, Verónica; Baigorri, Roberto; Fuentes, Marta; Zamarreño, Angel Maria; Berbara, Ricardo Luis Louro; Garcia-Mina, José María

2016-01-01

The importance of soil humus in soil fertility has been well established many years ago. However, the knowledge about the whole mechanisms by which humic molecules in the rhizosphere improve plant growth remains partial and rather fragmentary. In this review we discuss the relationships between two main signaling pathway families that are affected by humic substances within the plant: one directly related to hormonal action and the other related to reactive oxygen species (ROS). In this sense, our aims are to try the integration of all these events in a more comprehensive model and underline some points in the model that remain unclear and deserve further research. PMID:27366744

MEASURING TRANSIT SIGNAL RECOVERY IN THE KEPLER PIPELINE. I. INDIVIDUAL EVENTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christiansen, Jessie L.; Clarke, Bruce D.; Burke, Christopher J.

The Kepler mission was designed to measure the frequency of Earth-size planets in the habitable zone of Sun-like stars. A crucial component for recovering the underlying planet population from a sample of detected planets is understanding the completeness of that sample-the fraction of the planets that could have been discovered in a given data set that actually were detected. Here, we outline the information required to determine the sample completeness, and describe an experiment to address a specific aspect of that question, i.e., the issue of transit signal recovery. We investigate the extent to which the Kepler pipeline preserves individualmore » transit signals by injecting simulated transits into the pixel-level data, processing the modified pixels through the pipeline, and comparing the measured transit signal-to-noise ratio (S/N) to that expected without perturbation by the pipeline. We inject simulated transit signals across the full focal plane for a set of observations for a duration of 89 days. On average, we find that the S/N of the injected signal is recovered at MS = 0.9973({+-} 0.0012) Multiplication-Sign BS - 0.0151({+-} 0.0049), where MS is the measured S/N and BS is the baseline, or expected, S/N. The 1{sigma} width of the distribution around this correlation is {+-}2.64%. This indicates an extremely high fidelity in reproducing the expected detection statistics for single transit events, and provides teams performing their own periodic transit searches the confidence that there is no systematic reduction in transit signal strength introduced by the pipeline. We discuss the pipeline processes that cause the measured S/N to deviate significantly from the baseline S/N for a small fraction of targets; these are primarily the handling of data adjacent to spacecraft re-pointings and the removal of harmonics prior to the measurement of the S/N. Finally, we outline the further work required to characterize the completeness of the Kepler pipeline.« less

TiD-Introducing and Benchmarking an Event-Delivery System for Brain-Computer Interfaces.

PubMed

Breitwieser, Christian; Tavella, Michele; Schreuder, Martijn; Cincotti, Febo; Leeb, Robert; Muller-Putz, Gernot R

2017-12-01

In this paper, we present and analyze an event distribution system for brain-computer interfaces. Events are commonly used to mark and describe incidents during an experiment and are therefore critical for later data analysis or immediate real-time processing. The presented approach, called Tools for brain-computer interaction interface D (TiD), delivers messages in XML format via a buslike system using transmission control protocol connections or shared memory. A dedicated server dispatches TiD messages to distributed or local clients. The TiD message is designed to be flexible and contains time stamps for event synchronization, whereas events describe incidents, which occur during an experiment. TiD was tested extensively toward stability and latency. The effect of an occurring event jitter was analyzed and benchmarked on a reference implementation under different conditions as gigabit and 100-Mb Ethernet or Wi-Fi with a different number of event receivers. A 3-dB signal attenuation, which occurs when averaging jitter influenced trials aligned by events, is starting to become visible at around 1-2 kHz in the case of a gigabit connection. Mean event distribution times across operating systems are ranging from 0.3 to 0.5ms for a gigabit network connection for 10 6 events. Results for other environmental conditions are available in this paper. References already using TiD for event distribution are provided showing the applicability of TiD for event delivery with distributed or local clients.

FRET and BRET-based biosensors in live cell compound screens.

PubMed

Robinson, Katie Herbst; Yang, Jessica R; Zhang, Jin

2014-01-01

Live cell compound screening with genetically encoded fluorescence or bioluminescence-based biosensors offers a potentially powerful approach to identify novel regulators of a signaling event of interest. In particular, compound screening in living cells has the added benefit that the entire signaling network remains intact, and thus the screen is not just against a single molecule of interest but against any molecule within the signaling network that may modulate the distinct signaling event reported by the biosensor in use. Furthermore, only molecules that are cell permeable or act at cell surface receptors will be identified as "hits," thus reducing further optimization of the compound in terms of cell penetration. Here we discuss a detailed protocol for using genetically encoded biosensors in living cells in a 96-well format for the execution of high throughput compound screens and the identification of small molecules which modulate a signaling event of interest.

Organotypic three-dimensional culture model of mesenchymal and epithelial cells to examine tissue fusion events.

EPA Science Inventory

Tissue fusion during early mammalian development requires coordination of multiple cell types, the extracellular matrix, and complex signaling pathways. Fusion events during processes including heart development, neural tube closure, and palatal fusion are dependent on signaling ...

Element analysis: a wavelet-based method for analysing time-localized events in noisy time series.

PubMed

Lilly, Jonathan M

2017-04-01

A method is derived for the quantitative analysis of signals that are composed of superpositions of isolated, time-localized 'events'. Here, these events are taken to be well represented as rescaled and phase-rotated versions of generalized Morse wavelets, a broad family of continuous analytic functions. Analysing a signal composed of replicates of such a function using another Morse wavelet allows one to directly estimate the properties of events from the values of the wavelet transform at its own maxima. The distribution of events in general power-law noise is determined in order to establish significance based on an expected false detection rate. Finally, an expression for an event's 'region of influence' within the wavelet transform permits the formation of a criterion for rejecting spurious maxima due to numerical artefacts or other unsuitable events. Signals can then be reconstructed based on a small number of isolated points on the time/scale plane. This method, termed element analysis , is applied to the identification of long-lived eddy structures in ocean currents as observed by along-track measurements of sea surface elevation from satellite altimetry.

An automatic microseismic or acoustic emission arrival identification scheme with deep recurrent neural networks

NASA Astrophysics Data System (ADS)

Zheng, Jing; Lu, Jiren; Peng, Suping; Jiang, Tianqi

2018-02-01

The conventional arrival pick-up algorithms cannot avoid the manual modification of the parameters for the simultaneous identification of multiple events under different signal-to-noise ratios (SNRs). Therefore, in order to automatically obtain the arrivals of multiple events with high precision under different SNRs, in this study an algorithm was proposed which had the ability to pick up the arrival of microseismic or acoustic emission events based on deep recurrent neural networks. The arrival identification was performed using two important steps, which included a training phase and a testing phase. The training process was mathematically modelled by deep recurrent neural networks using Long Short-Term Memory architecture. During the testing phase, the learned weights were utilized to identify the arrivals through the microseismic/acoustic emission data sets. The data sets were obtained by rock physics experiments of the acoustic emission. In order to obtain the data sets under different SNRs, this study added random noise to the raw experiments' data sets. The results showed that the outcome of the proposed method was able to attain an above 80 per cent hit-rate at SNR 0 dB, and an approximately 70 per cent hit-rate at SNR -5 dB, with an absolute error in 10 sampling points. These results indicated that the proposed method had high selection precision and robustness.

A low-noise wide-dynamic-range event-driven detector using SOI pixel technology for high-energy particle imaging

NASA Astrophysics Data System (ADS)

Shrestha, Sumeet; Kamehama, Hiroki; Kawahito, Shoji; Yasutomi, Keita; Kagawa, Keiichiro; Takeda, Ayaki; Tsuru, Takeshi Go; Arai, Yasuo

2015-08-01

This paper presents a low-noise wide-dynamic-range pixel design for a high-energy particle detector in astronomical applications. A silicon on insulator (SOI) based detector is used for the detection of wide energy range of high energy particles (mainly for X-ray). The sensor has a thin layer of SOI CMOS readout circuitry and a thick layer of high-resistivity detector vertically stacked in a single chip. Pixel circuits are divided into two parts; signal sensing circuit and event detection circuit. The event detection circuit consisting of a comparator and logic circuits which detect the incidence of high energy particle categorizes the incident photon it into two energy groups using an appropriate energy threshold and generate a two-bit code for an event and energy level. The code for energy level is then used for selection of the gain of the in-pixel amplifier for the detected signal, providing a function of high-dynamic-range signal measurement. The two-bit code for the event and energy level is scanned in the event scanning block and the signals from the hit pixels only are read out. The variable-gain in-pixel amplifier uses a continuous integrator and integration-time control for the variable gain. The proposed design allows the small signal detection and wide dynamic range due to the adaptive gain technique and capability of correlated double sampling (CDS) technique of kTC noise canceling of the charge detector.

Phasic dopamine release drives rapid activation of striatal D2-receptors

PubMed Central

Marcott, Pamela F; Mamaligas, Aphroditi A; Ford, Christopher P

2014-01-01

Summary Striatal dopamine transmission underlies numerous goal-directed behaviors. Medium spiny neurons (MSNs) are a major target of dopamine in the striatum. However, as dopamine does not directly evoke a synaptic event in MSNs, the time course of dopamine signaling in these cells remains unclear. To examine how dopamine release activates D2-receptors on MSNs, G-protein activated inwardly rectifying potassium (GIRK2; Kir 3.2) channels were virally overexpressed in the striatum and the resulting outward currents were used as a sensor of D2-receptor activation. Electrical and optogenetic stimulation of dopamine terminals evoked robust D2-receptor inhibitory post-synaptic currents (IPSCs) in GIRK2-expressing MSNs that occurred in under a second. Evoked D2-IPSCs could be driven by repetitive stimulation and were not occluded by background dopamine tone. Together, the results indicate that D2-receptors on MSNs exhibit functional low affinity and suggest that striatal D2-receptors can encode both tonic and phasic dopamine signals. PMID:25242218

Can machine learning complement traditional medical device surveillance? A case study of dual-chamber implantable cardioverter-defibrillators.

PubMed

Ross, Joseph S; Bates, Jonathan; Parzynski, Craig S; Akar, Joseph G; Curtis, Jeptha P; Desai, Nihar R; Freeman, James V; Gamble, Ginger M; Kuntz, Richard; Li, Shu-Xia; Marinac-Dabic, Danica; Masoudi, Frederick A; Normand, Sharon-Lise T; Ranasinghe, Isuru; Shaw, Richard E; Krumholz, Harlan M

2017-01-01

Machine learning methods may complement traditional analytic methods for medical device surveillance. Using data from the National Cardiovascular Data Registry for implantable cardioverter-defibrillators (ICDs) linked to Medicare administrative claims for longitudinal follow-up, we applied three statistical approaches to safety-signal detection for commonly used dual-chamber ICDs that used two propensity score (PS) models: one specified by subject-matter experts (PS-SME), and the other one by machine learning-based selection (PS-ML). The first approach used PS-SME and cumulative incidence (time-to-event), the second approach used PS-SME and cumulative risk (Data Extraction and Longitudinal Trend Analysis [DELTA]), and the third approach used PS-ML and cumulative risk (embedded feature selection). Safety-signal surveillance was conducted for eleven dual-chamber ICD models implanted at least 2,000 times over 3 years. Between 2006 and 2010, there were 71,948 Medicare fee-for-service beneficiaries who received dual-chamber ICDs. Cumulative device-specific unadjusted 3-year event rates varied for three surveyed safety signals: death from any cause, 12.8%-20.9%; nonfatal ICD-related adverse events, 19.3%-26.3%; and death from any cause or nonfatal ICD-related adverse event, 27.1%-37.6%. Agreement among safety signals detected/not detected between the time-to-event and DELTA approaches was 90.9% (360 of 396, k =0.068), between the time-to-event and embedded feature-selection approaches was 91.7% (363 of 396, k =-0.028), and between the DELTA and embedded feature selection approaches was 88.1% (349 of 396, k =-0.042). Three statistical approaches, including one machine learning method, identified important safety signals, but without exact agreement. Ensemble methods may be needed to detect all safety signals for further evaluation during medical device surveillance.

Infrasonic Signals from the 29 June 2012 Derecho

NASA Astrophysics Data System (ADS)

Winslow, N.; Howard, W. B.; Pulli, J. J.; Kofford, A. S.

2012-12-01

Common weather events such as pressure fronts, tornados, and hurricanes generate infrasonic signals (sub-audible acoustic signals with an oscillatory frequency below 20 Hz). These signals can provide a distal (>10km) analysis of weather events because: (1) the attenuation of an infrasonic signal with distance is less than that of a similar audible signal, and (2) the propagation velocities of typical weather events are much slower than the speed of sound. The 29 June, 2012 Derecho (a widespread, long-lived, rapidly moving linear band of storms extending more than 240 miles and including wind gusts in excess of 58 mph) that stretched from Chicago, IL to Washington, DC generated infrasonic signals in addition to causing over $100 million in damage to the power systems of Virginia, West Virginia, and Maryland alone. The infrasonic (and seismic) signals from this event were recorded on the NCPA micro barometers along the northeastern edge of the current configuration of the USArray. These instruments, which sample at 40 Hz, exhibit a flat frequency response from around 0.1 Hz to above 20 Hz and show a sensitivity of 1.57 x 104 Volts/Pascal at 0.8 Hz. An analysis of the recordings observed at multiple stations identified several infrasonic signatures from the Derecho. The signal's duration was approximately 40 minutes and exhibited a large peak pressure fluctuation. A characteristic ramp up occurred before the peak pressure fluctuation, and the majority of the infrasonic energy occurred below 1 Hz. These signatures are analyzed within the context of the Derecho as an infrasonic source, and the propagation of infrasound in the atmosphere.

Oxidative Stress, Redox Signaling, and Autophagy: Cell Death Versus Survival

PubMed Central

Navarro-Yepes, Juliana; Burns, Michaela; Anandhan, Annadurai; Khalimonchuk, Oleh; del Razo, Luz Maria; Quintanilla-Vega, Betzabet; Pappa, Aglaia; Panayiotidis, Mihalis I.

2014-01-01

Abstract Significance: The molecular machinery regulating autophagy has started becoming elucidated, and a number of studies have undertaken the task to determine the role of autophagy in cell fate determination within the context of human disease progression. Oxidative stress and redox signaling are also largely involved in the etiology of human diseases, where both survival and cell death signaling cascades have been reported to be modulated by reactive oxygen species (ROS) and reactive nitrogen species (RNS). Recent Advances: To date, there is a good understanding of the signaling events regulating autophagy, as well as the signaling processes by which alterations in redox homeostasis are transduced to the activation/regulation of signaling cascades. However, very little is known about the molecular events linking them to the regulation of autophagy. This lack of information has hampered the understanding of the role of oxidative stress and autophagy in human disease progression. Critical Issues: In this review, we will focus on (i) the molecular mechanism by which ROS/RNS generation, redox signaling, and/or oxidative stress/damage alter autophagic flux rates; (ii) the role of autophagy as a cell death process or survival mechanism in response to oxidative stress; and (iii) alternative mechanisms by which autophagy-related signaling regulate mitochondrial function and antioxidant response. Future Directions: Our research efforts should now focus on understanding the molecular basis of events by which autophagy is fine tuned by oxidation/reduction events. This knowledge will enable us to understand the mechanisms by which oxidative stress and autophagy regulate human diseases such as cancer and neurodegenerative disorders. Antioxid. Redox Signal. 21, 66–85. PMID:24483238

Method for triggering an action

DOEpatents

Hall, David R.; Bartholomew, David B.; Johnson, Monte L.; Moon, Justin; Koehler, Roger O.

2006-10-17

A method for triggering an action of at least one downhole device on a downhole network integrated into a downhole tool string synchronized to an event comprises determining latency, sending a latency adjusted signal, and performing the action. The latency is determined between a control device and the at least one downhole device. The latency adjusted signal for triggering an action is sent to the downhole device. The action is performed downhole synchronized to the event. A preferred method for determining latency comprises the steps: a control device sends a first signal to the downhole device; after receiving the signal, the downhole device sends a response signal to the control device; and the control device analyzes the time from sending the signal to receiving the response signal.

Genome-Wide Association Study (GWAS) and Genome-Wide Environment Interaction Study (GWEIS) of Depressive Symptoms in African American and Hispanic/Latina Women

PubMed Central

Dunn, Erin C.; Wiste, Anna; Radmanesh, Farid; Almli, Lynn M.; Gogarten, Stephanie M.; Sofer, Tamar; Faul, Jessica D.; Kardia, Sharon L.R.; Smith, Jennifer A.; Weir, David R.; Zhao, Wei; Soare, Thomas W.; Mirza, Saira S.; Hek, Karin; Tiemeier, Henning W.; Goveas, Joseph S.; Sarto, Gloria E.; Snively, Beverly M.; Cornelis, Marilyn; Koenen, Karestan C.; Kraft, Peter; Purcell, Shaun; Ressler, Kerry J.; Rosand, Jonathan; Wassertheil-Smoller, Sylvia; Smoller, Jordan W.

2016-01-01

Background Genome-wide association studies (GWAS) have been unable to identify variants linked to depression. We hypothesized that examining depressive symptoms and considering gene-environment interaction (G×E) might improve efficiency for gene discovery. We therefore conducted a GWAS and genome-wide environment interaction study (GWEIS) of depressive symptoms. Methods Using data from the SHARe cohort of the Women’s Health Initiative, comprising African Americans (n=7179) and Hispanics/Latinas (n=3138), we examined genetic main effects and G×E with stressful life events and social support. We also conducted a heritability analysis using genome-wide complex trait analysis (GCTA). Replication was attempted in four independent cohorts. Results No SNPs achieved genome-wide significance for main effects in either discovery sample. The top signals in African Americans were rs73531535 (located 20kb from GPR139, p=5.75×10−8) and rs75407252 (intronic to CACNA2D3, p=6.99×10−7). In Hispanics/Latinas, the top signals were rs2532087 (located 27kb from CD38, p=2.44×10−7) and rs4542757 (intronic to DCC, p=7.31×10−7). In the GWEIS with stressful life events, one interaction signal was genome-wide significant in African Americans (rs4652467; p=4.10×10−10; located 14kb from CEP350). This interaction was not observed in a smaller replication cohort. Although heritability estimates for depressive symptoms and stressful life events were each less than 10%, they were strongly genetically correlated (rG=0.95), suggesting that common variation underlying depressive symptoms and stressful life event exposure, though modest on their own, were highly overlapping in this sample. Conclusions Our results underscore the need for larger samples, more GWEIS, and greater investigation into genetic and environmental determinants of depressive symptoms in minorities. PMID:27038408

GENOME-WIDE ASSOCIATION STUDY (GWAS) AND GENOME-WIDE BY ENVIRONMENT INTERACTION STUDY (GWEIS) OF DEPRESSIVE SYMPTOMS IN AFRICAN AMERICAN AND HISPANIC/LATINA WOMEN.

PubMed

Dunn, Erin C; Wiste, Anna; Radmanesh, Farid; Almli, Lynn M; Gogarten, Stephanie M; Sofer, Tamar; Faul, Jessica D; Kardia, Sharon L R; Smith, Jennifer A; Weir, David R; Zhao, Wei; Soare, Thomas W; Mirza, Saira S; Hek, Karin; Tiemeier, Henning; Goveas, Joseph S; Sarto, Gloria E; Snively, Beverly M; Cornelis, Marilyn; Koenen, Karestan C; Kraft, Peter; Purcell, Shaun; Ressler, Kerry J; Rosand, Jonathan; Wassertheil-Smoller, Sylvia; Smoller, Jordan W

2016-04-01

Genome-wide association studies (GWAS) have made little progress in identifying variants linked to depression. We hypothesized that examining depressive symptoms and considering gene-environment interaction (GxE) might improve efficiency for gene discovery. We therefore conducted a GWAS and genome-wide by environment interaction study (GWEIS) of depressive symptoms. Using data from the SHARe cohort of the Women's Health Initiative, comprising African Americans (n = 7,179) and Hispanics/Latinas (n = 3,138), we examined genetic main effects and GxE with stressful life events and social support. We also conducted a heritability analysis using genome-wide complex trait analysis (GCTA). Replication was attempted in four independent cohorts. No SNPs achieved genome-wide significance for main effects in either discovery sample. The top signals in African Americans were rs73531535 (located 20 kb from GPR139, P = 5.75 × 10(-8) ) and rs75407252 (intronic to CACNA2D3, P = 6.99 × 10(-7) ). In Hispanics/Latinas, the top signals were rs2532087 (located 27 kb from CD38, P = 2.44 × 10(-7) ) and rs4542757 (intronic to DCC, P = 7.31 × 10(-7) ). In the GEWIS with stressful life events, one interaction signal was genome-wide significant in African Americans (rs4652467; P = 4.10 × 10(-10) ; located 14 kb from CEP350). This interaction was not observed in a smaller replication cohort. Although heritability estimates for depressive symptoms and stressful life events were each less than 10%, they were strongly genetically correlated (rG = 0.95), suggesting that common variation underlying self-reported depressive symptoms and stressful life event exposure, though modest on their own, were highly overlapping in this sample. Our results underscore the need for larger samples, more GEWIS, and greater investigation into genetic and environmental determinants of depressive symptoms in minorities. © 2016 Wiley Periodicals, Inc.

L-Band Ionosphere Scintillations Observed by A GNSS Receiver Array at HAARP

NASA Astrophysics Data System (ADS)

Morton, Y.; Pelgrum, W.; van Graas, F.

2011-12-01

As we enter a new solar maximum period, GNSS receivers, especially the ones operating in high latitude and equatorial regions, are facing an increasing threat from ionosphere scintillations. The increased solar activities, however, also offer a great opportunity to collect scintillation data to gain better understandings of scintillation effects on GNSS signals. During the past decade, many GPS receivers have been deployed around the globe to monitor ionosphere scintillations. Most of these GPS receivers are commercial receivers whose tracking mechanisms are not designed to operate under ionosphere scintillation. When strong scintillations occur, these receivers will either generate erroneous outputs or completely lose lock. Even when the scintillation is mild, the tracking loop outputs are not true representation of the signal parameters due the tracking loop transfer function. High quality, unprocessed GNSS receiver front end raw IF samples collected during ionosphere scintillations are necessary to produce realistic scintillation signal parameter estimations. In this presentation, we will update our effort in establishing a unique GNSS receiver array at HAARP, Alaska to collect GPS and GLONASS satellite signals at various stages of the GNSS receiver processing. Signal strength, carrier phase, and relative TEC measurements generated by the receiver array as well as additional on-site diagnostic instrumentation measurements obtained from two active heating experiment campaigns conducted in 2011 will be presented. Additionally, we will also highlight and contrast the artificial heating experiment results with observations of natural scintillation events captured by our receivers using an automatic event trigger mechanism during the past year. These interesting results demonstrate the feasibility and effectiveness of our experimental data collection system in providing insightful details of ionosphere responses to active perturbations and natural disturbances.

Improved Contrast-Enhanced Ultrasound Imaging With Multiplane-Wave Imaging.

PubMed

Gong, Ping; Song, Pengfei; Chen, Shigao

2018-02-01

Contrast-enhanced ultrasound (CEUS) imaging has great potential for use in new ultrasound clinical applications such as myocardial perfusion imaging and abdominal lesion characterization. In CEUS imaging, contrast agents (i.e., microbubbles) are used to improve contrast between blood and tissue because of their high nonlinearity under low ultrasound pressure. However, the quality of CEUS imaging sometimes suffers from a low signal-to-noise ratio (SNR) in deeper imaging regions when a low mechanical index (MI) is used to avoid microbubble disruption, especially for imaging at off-resonance transmit frequencies. In this paper, we propose a new strategy of combining CEUS sequences with the recently proposed multiplane-wave (MW) compounding method to improve the SNR of CEUS in deeper imaging regions without increasing MI or sacrificing frame rate. The MW-CEUS method emits multiple Hadamard-coded CEUS pulses in each transmission event (i.e., pulse-echo event). The received echo signals first undergo fundamental bandpass filtering (i.e., the filter is centered on the transmit frequency) to eliminate the microbubble's second-harmonic signals because they cannot be encoded by pulse inversion. The filtered signals are then Hadamard decoded and realigned in fast time to recover the signals as they would have been obtained using classic CEUS pulses, followed by designed recombination to cancel the linear tissue responses. The MW-CEUS method significantly improved contrast-to-tissue ratio and SNR of CEUS imaging by transmitting longer coded pulses. The image resolution was also preserved. The microbubble disruption ratio and motion artifacts in MW-CEUS were similar to those of classic CEUS imaging. In addition, the MW-CEUS sequence can be adapted to other transmission coding formats. These properties of MW-CEUS can potentially facilitate CEUS imaging for many clinical applications, especially assessing deep abdominal organs or the heart.

Estimation of red-light running frequency using high-resolution traffic and signal data.

PubMed

Chen, Peng; Yu, Guizhen; Wu, Xinkai; Ren, Yilong; Li, Yueguang

2017-05-01

Red-light-running (RLR) emerges as a major cause that may lead to intersection-related crashes and endanger intersection safety. To reduce RLR violations, it's critical to identify the influential factors associated with RLR and estimate RLR frequency. Without resorting to video camera recordings, this study investigates this important issue by utilizing high-resolution traffic and signal event data collected from loop detectors at five intersections on Trunk Highway 55, Minneapolis, MN. First, a simple method is proposed to identify RLR by fully utilizing the information obtained from stop bar detectors, downstream entrance detectors and advance detectors. Using 12 months of event data, a total of 6550 RLR cases were identified. According to a definition of RLR frequency as the conditional probability of RLR on a certain traffic or signal condition (veh/1000veh), the relationships between RLR frequency and some influential factors including arriving time at advance detector, approaching speed, headway, gap to the preceding vehicle on adjacent lane, cycle length, geometric characteristics and even snowing weather were empirically investigated. Statistical analysis shows good agreement with the traffic engineering practice, e.g., RLR is most likely to occur on weekdays during peak periods under large traffic demands and longer signal cycles, and a total of 95.24% RLR events occurred within the first 1.5s after the onset of red phase. The findings confirmed that vehicles tend to run the red light when they are close to intersection during phase transition, and the vehicles following the leading vehicle with short headways also likely run the red light. Last, a simplified nonlinear regression model is proposed to estimate RLR frequency based on the data from advance detector. The study is expected to helpbetter understand RLR occurrence and further contribute to the future improvement of intersection safety. Copyright © 2017 Elsevier Ltd. All rights reserved.

Failures of cognitive control or attention? The case of stop-signal deficits in schizophrenia.

PubMed

Matzke, Dora; Hughes, Matthew; Badcock, Johanna C; Michie, Patricia; Heathcote, Andrew

2017-05-01

We used Bayesian cognitive modelling to identify the underlying causes of apparent inhibitory deficits in the stop-signal paradigm. The analysis was applied to stop-signal data reported by Badcock et al. (Psychological Medicine 32: 87-297, 2002) and Hughes et al. (Biological Psychology 89: 220-231, 2012), where schizophrenia patients and control participants made rapid choice responses, but on some trials were signalled to stop their ongoing response. Previous research has assumed an inhibitory deficit in schizophrenia, because estimates of the mean time taken to react to the stop signal are longer in patients than controls. We showed that these longer estimates are partly due to failing to react to the stop signal ("trigger failures") and partly due to a slower initiation of inhibition, implicating a failure of attention rather than a deficit in the inhibitory process itself. Correlations between the probability of trigger failures and event-related potentials reported by Hughes et al. are interpreted as supporting the attentional account of inhibitory deficits. Our results, and those of Matzke et al. (2016), who report that controls also display a substantial although lower trigger-failure rate, indicate that attentional factors need to be taken into account when interpreting results from the stop-signal paradigm.

Exosome uptake depends on ERK1/2-heat shock protein 27 signaling and lipid Raft-mediated endocytosis negatively regulated by caveolin-1.

PubMed

Svensson, Katrin J; Christianson, Helena C; Wittrup, Anders; Bourseau-Guilmain, Erika; Lindqvist, Eva; Svensson, Lena M; Mörgelin, Matthias; Belting, Mattias

2013-06-14

The role of exosomes in cancer can be inferred from the observation that they transfer tumor cell derived genetic material and signaling proteins, resulting in e.g. increased tumor angiogenesis and metastasis. However, the membrane transport mechanisms and the signaling events involved in the uptake of these virus-like particles remain ill-defined. We now report that internalization of exosomes derived from glioblastoma (GBM) cells involves nonclassical, lipid raft-dependent endocytosis. Importantly, we show that the lipid raft-associated protein caveolin-1 (CAV1), in analogy with its previously described role in virus uptake, negatively regulates the uptake of exosomes. We find that exosomes induce the phosphorylation of several downstream targets known to associate with lipid rafts as signaling and sorting platforms, such as extracellular signal-regulated kinase-1/2 (ERK1/2) and heat shock protein 27 (HSP27). Interestingly, exosome uptake appears dependent on unperturbed ERK1/2-HSP27 signaling, and ERK1/2 phosphorylation is under negative influence by CAV1 during internalization of exosomes. These findings significantly advance our general understanding of exosome-mediated uptake and offer potential strategies for how this pathway may be targeted through modulation of CAV1 expression and ERK1/2 signaling.

Optical switches for remote and noninvasive control of cell signaling.

PubMed

Gorostiza, Pau; Isacoff, Ehud Y

2008-10-17

Although the identity and interactions of signaling proteins have been studied in great detail, the complexity of signaling networks cannot be fully understood without elucidating the timing and location of activity of individual proteins. To do this, one needs a means for detecting and controlling specific signaling events. An attractive approach is to use light, both to report on and control signaling proteins in cells, because light can probe cells in real time with minimal damage. Although optical detection of signaling events has been successful for some time, the development of the means for optical control has accelerated only recently. Of particular interest is the development of chemically engineered proteins that are directly sensitive to light.

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

NASA Astrophysics Data System (ADS)

Kolarski, A.; Grubor, D.

2015-12-01

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

Midbrain dopamine neurons signal aversion in a reward-context-dependent manner

PubMed Central

Matsumoto, Hideyuki; Tian, Ju; Uchida, Naoshige; Watabe-Uchida, Mitsuko

2016-01-01

Dopamine is thought to regulate learning from appetitive and aversive events. Here we examined how optogenetically-identified dopamine neurons in the lateral ventral tegmental area of mice respond to aversive events in different conditions. In low reward contexts, most dopamine neurons were exclusively inhibited by aversive events, and expectation reduced dopamine neurons’ responses to reward and punishment. When a single odor predicted both reward and punishment, dopamine neurons’ responses to that odor reflected the integrated value of both outcomes. Thus, in low reward contexts, dopamine neurons signal value prediction errors (VPEs) integrating information about both reward and aversion in a common currency. In contrast, in high reward contexts, dopamine neurons acquired a short-latency excitation to aversive events that masked their VPE signaling. Our results demonstrate the importance of considering the contexts to examine the representation in dopamine neurons and uncover different modes of dopamine signaling, each of which may be adaptive for different environments. DOI: http://dx.doi.org/10.7554/eLife.17328.001 PMID:27760002

Applications of Wavelet Transform and Fuzzy Neural Network on Power Quality Recognition

NASA Astrophysics Data System (ADS)

Liao, Chiung-Chou; Yang, Hong-Tzer; Lin, Ying-Chun

2008-10-01

The wavelet transform coefficients (WTCs) contain plenty of information needed for transient event identification of power quality (PQ) events. However, adopting WTCs directly has the drawbacks of taking a longer time and too much memory for the recognition system. To solve the abovementioned recognition problems and to effectively reduce the number of features representing power transients, spectrum energies of WTCs in different scales are calculated by Parseval's Theorem. Through the proposed approach, features of the original power signals can be reserved and not influenced by occurring points of PQ events. The fuzzy neural classification systems are then used for signal recognition and fuzzy rule construction. Success rates of recognizing PQ events from noise-riding signals are proven to be feasible in power system applications in this paper.

Rules for Scoring Respiratory Events in Sleep: Update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events

PubMed Central

Berry, Richard B.; Budhiraja, Rohit; Gottlieb, Daniel J.; Gozal, David; Iber, Conrad; Kapur, Vishesh K.; Marcus, Carole L.; Mehra, Reena; Parthasarathy, Sairam; Quan, Stuart F.; Redline, Susan; Strohl, Kingman P.; Ward, Sally L. Davidson; Tangredi, Michelle M.

2012-01-01

The American Academy of Sleep Medicine (AASM) Sleep Apnea Definitions Task Force reviewed the current rules for scoring respiratory events in the 2007 AASM Manual for the Scoring and Sleep and Associated Events to determine if revision was indicated. The goals of the task force were (1) to clarify and simplify the current scoring rules, (2) to review evidence for new monitoring technologies relevant to the scoring rules, and (3) to strive for greater concordance between adult and pediatric rules. The task force reviewed the evidence cited by the AASM systematic review of the reliability and validity of scoring respiratory events published in 2007 and relevant studies that have appeared in the literature since that publication. Given the limitations of the published evidence, a consensus process was used to formulate the majority of the task force recommendations concerning revisions. The task force made recommendations concerning recommended and alternative sensors for the detection of apnea and hypopnea to be used during diagnostic and positive airway pressure (PAP) titration polysomnography. An alternative sensor is used if the recommended sensor fails or the signal is inaccurate. The PAP device flow signal is the recommended sensor for the detection of apnea, hypopnea, and respiratory effort related arousals (RERAs) during PAP titration studies. Appropriate filter settings for recording (display) of the nasal pressure signal to facilitate visualization of inspiratory flattening are also specified. The respiratory inductance plethysmography (RIP) signals to be used as alternative sensors for apnea and hypopnea detection are specified. The task force reached consensus on use of the same sensors for adult and pediatric patients except for the following: (1) the end-tidal PCO2 signal can be used as an alternative sensor for apnea detection in children only, and (2) polyvinylidene fluoride (PVDF) belts can be used to monitor respiratory effort (thoracoabdominal belts) and as an alternative sensor for detection of apnea and hypopnea (PVDFsum) only in adults. The task force recommends the following changes to the 2007 respiratory scoring rules. Apnea in adults is scored when there is a drop in the peak signal excursion by ≥ 90% of pre-event baseline using an oronasal thermal sensor (diagnostic study), PAP device flow (titration study), or an alternative apnea sensor, for ≥ 10 seconds. Hypopnea in adults is scored when the peak signal excursions drop by ≥ 30% of pre-event baseline using nasal pressure (diagnostic study), PAP device flow (titration study), or an alternative sensor, for ≥ 10 seconds in association with either ≥ 3% arterial oxygen desaturation or an arousal. Scoring a hypopnea as either obstructive or central is now listed as optional, and the recommended scoring rules are presented. In children an apnea is scored when peak signal excursions drop by ≥ 90% of pre-event baseline using an oronasal thermal sensor (diagnostic study), PAP device flow (titration study), or an alternative sensor; and the event meets duration and respiratory effort criteria for an obstructive, mixed, or central apnea. A central apnea is scored in children when the event meets criteria for an apnea, there is an absence of inspiratory effort throughout the event, and at least one of the following is met: (1) the event is ≥ 20 seconds in duration, (2) the event is associated with an arousal or ≥ 3% oxygen desaturation, (3) (infants under 1 year of age only) the event is associated with a decrease in heart rate to less than 50 beats per minute for at least 5 seconds or less than 60 beats per minute for 15 seconds. A hypopnea is scored in children when the peak signal excursions drop is ≥ 30% of pre-event baseline using nasal pressure (diagnostic study), PAP device flow (titration study), or an alternative sensor, for ≥ the duration of 2 breaths in association with either ≥ 3% oxygen desaturation or an arousal. In children and adults, surrogates of the arterial PCO2 are the end-tidal PCO2 or transcutaneous PCO2 (diagnostic study) or transcutaneous PCO2 (titration study). For adults, sleep hypoventilation is scored when the arterial PCO2 (or surrogate) is > 55 mm Hg for ≥ 10 minutes or there is an increase in the arterial PCO2 (or surrogate) ≥ 10 mm Hg (in comparison to an awake supine value) to a value exceeding 50 mm Hg for ≥ 10 minutes. For pediatric patients hypoventilation is scored when the arterial PCO2 (or surrogate) is > 50 mm Hg for > 25% of total sleep time. In adults Cheyne-Stokes breathing is scored when both of the following are met: (1) there are episodes of ≥ 3 consecutive central apneas and/or central hypopneas separated by a crescendo and decrescendo change in breathing amplitude with a cycle length of at least 40 seconds (typically 45 to 90 seconds), and (2) there are five or more central apneas and/or central hypopneas per hour associated with the crescendo/decrescendo breathing pattern recorded over a minimum of 2 hours of monitoring. Commentary: A commentary on this article appears in this issue on page 621. Citation: Berry RB; Budhiraja R; Gottlieb DJ; Gozal D; Iber C; Kapur VK; Marcus CL; Mehra R; Parthasarathy S; Quan SF; Redline S; Strohl KP; Ward SLD; Tangredi MM. Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. J Clin Sleep Med 2012;8(5):597-619. PMID:23066376

Acidosis promotes invasiveness of breast cancer cells through ROS-AKT-NF-κB pathway

PubMed Central

Gupta, Subash C.; Singh, Ramesh; Pochampally, Radhika; Watabe, Kounosuke; Mo, Yin-Yuan

2014-01-01

It is well known that acidic microenvironment promotes tumorigenesis, however, the underlying mechanism remains largely unknown. In the present study, we show that acidosis promotes invasiveness of breast cancer cells through a series of signaling events. First, our study indicates that NF-κB is a key factor for acidosis-induced cell invasion. Acidosis activates NF-κB without affecting STAT3 activity; knockdown of NF-κB p65 abrogates the acidosis-induced invasion activity. Next, we show that the activation of NF-κB is mediated through phosphorylation and degradation of IκBα; and phosphorylation and nuclear translocation of p65. Upstream to NF-κB signaling, AKT is activated under acidic conditions. Moreover, acidosis induces generation of reactive oxygen species (ROS) which can be suppressed by ROS scavengers, reversing the acidosis-induced activation of AKT and NF-κB, and invasiveness. As a negative regulator of AKT, PTEN is oxidized and inactivated by the acidosis-induced ROS. Finally, inhibition of NADPH oxidase (NOX) suppresses acidosis-induced ROS production, suggesting involvement of NOX in acidosis-induced signaling cascade. Of considerable interest, acidosis-induced ROS production and activation of AKT and NF-κB can be only detected in cancer cells, but not in non-malignant cells. Together, these results demonstrate a cancer specific acidosis-induced signaling cascade in breast cancer cells, leading to cell invasion. PMID:25504433

Method and apparatus for distinguishing actual sparse events from sparse event false alarms

DOEpatents

Spalding, Richard E.; Grotbeck, Carter L.

2000-01-01

Remote sensing method and apparatus wherein sparse optical events are distinguished from false events. "Ghost" images of actual optical phenomena are generated using an optical beam splitter and optics configured to direct split beams to a single sensor or segmented sensor. True optical signals are distinguished from false signals or noise based on whether the ghost image is presence or absent. The invention obviates the need for dual sensor systems to effect a false target detection capability, thus significantly reducing system complexity and cost.

Characterization of Strombolian events by using independent component analysis

NASA Astrophysics Data System (ADS)

Ciaramella, A.; de Lauro, E.; de Martino, S.; di Lieto, B.; Falanga, M.; Tagliaferri, R.

2004-10-01

We apply Independent Component Analysis (ICA) to seismic signals recorded at Stromboli volcano. Firstly, we show how ICA works considering synthetic signals, which are generated by dynamical systems. We prove that Strombolian signals, both tremor and explosions, in the high frequency band (>0.5 Hz), are similar in time domain. This seems to give some insights to the organ pipe model generation for the source of these events. Moreover, we are able to recognize in the tremor signals a low frequency component (<0.5 Hz), with a well defined peak corresponding to 30s.

Real-time classification of signals from three-component seismic sensors using neural nets

NASA Astrophysics Data System (ADS)

Bowman, B. C.; Dowla, F.

1992-05-01

Adaptive seismic data acquisition systems with capabilities of signal discrimination and event classification are important in treaty monitoring, proliferation, and earthquake early detection systems. Potential applications include monitoring underground chemical explosions, as well as other military, cultural, and natural activities where characteristics of signals change rapidly and without warning. In these applications, the ability to detect and interpret events rapidly without falling behind the influx of the data is critical. We developed a system for real-time data acquisition, analysis, learning, and classification of recorded events employing some of the latest technology in computer hardware, software, and artificial neural networks methods. The system is able to train dynamically, and updates its knowledge based on new data. The software is modular and hardware-independent; i.e., the front-end instrumentation is transparent to the analysis system. The software is designed to take advantage of the multiprocessing environment of the Unix operating system. The Unix System V shared memory and static RAM protocols for data access and the semaphore mechanism for interprocess communications were used. As the three-component sensor detects a seismic signal, it is displayed graphically on a color monitor using X11/Xlib graphics with interactive screening capabilities. For interesting events, the triaxial signal polarization is computed, a fast Fourier Transform (FFT) algorithm is applied, and the normalized power spectrum is transmitted to a backpropagation neural network for event classification. The system is currently capable of handling three data channels with a sampling rate of 500 Hz, which covers the bandwidth of most seismic events. The system has been tested in laboratory setting with artificial events generated in the vicinity of a three-component sensor.

Leucine modulates dynamic phosphorylation events in insulin signaling pathway and enhances insulin-dependent glycogen synthesis in human skeletal muscle cells

PubMed Central

2014-01-01

Background Branched-chain amino acids, especially leucine, are known to interact with insulin signaling pathway and glucose metabolism. However, the mechanism by which this is exerted, remain to be clearly defined. In order to examine the effect of leucine on muscle insulin signaling, a set of experiments was carried out to quantitate phosphorylation events along the insulin signaling pathway in human skeletal muscle cell cultures. Cells were exposed to insulin, leucine or both, and phosphorylation events of key insulin signaling molecules were tracked over time so as to monitor time-related responses that characterize the signaling events and could be missed by a single sampling strategy limited to pre/post stimulus events. Results Leucine is shown to increase the magnitude of insulin-dependent phosphorylation of protein kinase B (AKT) at Ser473 and glycogen synthase kinase (GSK3β) at Ser21-9. Glycogen synthesis follows the same pattern of GSK3β, with a significant increase at 100 μM leucine plus insulin stimulus. Moreover, data do not show any statistically significant increase of pGSK3β and glycogen synthesis at higher leucine concentrations. Leucine is also shown to increase the magnitude of insulin-mediated extracellularly regulated kinase (ERK) phosphorylation; however, differently from AKT and GSK3β, ERK shows a transient behavior, with an early peak response, followed by a return to the baseline condition. Conclusions These experiments demonstrate a complementary effect of leucine on insulin signaling in a human skeletal muscle cell culture, promoting insulin-activated GSK3β phosphorylation and glycogen synthesis. PMID:24646332

Effect of database profile variation on drug safety assessment: an analysis of spontaneous adverse event reports of Japanese cases

PubMed Central

Nomura, Kaori; Takahashi, Kunihiko; Hinomura, Yasushi; Kawaguchi, Genta; Matsushita, Yasuyuki; Marui, Hiroko; Anzai, Tatsuhiko; Hashiguchi, Masayuki; Mochizuki, Mayumi

2015-01-01

Background The use of a statistical approach to analyze cumulative adverse event (AE) reports has been encouraged by regulatory authorities. However, data variations affect statistical analyses (eg, signal detection). Further, differences in regulations, social issues, and health care systems can cause variations in AE data. The present study examined similarities and differences between two publicly available databases, ie, the Japanese Adverse Drug Event Report (JADER) database and the US Food and Drug Administration Adverse Event Reporting System (FAERS), and how they affect signal detection. Methods Two AE data sources from 2010 were examined, ie, JADER cases (JP) and Japanese cases extracted from the FAERS (FAERS-JP). Three methods for signals of disproportionate reporting, ie, the reporting odds ratio, Bayesian confidence propagation neural network, and Gamma Poisson Shrinker (GPS), were used on drug-event combinations for three substances frequently recorded in both systems. Results The two databases showed similar elements of AE reports, but no option was provided for a shareable case identifier. The average number of AEs per case was 1.6±1.3 (maximum 37) in the JP and 3.3±3.5 (maximum 62) in the FAERS-JP. Between 5% and 57% of all AEs were signaled by three quantitative methods for etanercept, infliximab, and paroxetine. Signals identified by GPS for the JP and FAERS-JP, as referenced by Japanese labeling, showed higher positive sensitivity than was expected. Conclusion The FAERS-JP was different from the JADER. Signals derived from both datasets identified different results, but shared certain signals. Discrepancies in type of AEs, drugs reported, and average number of AEs per case were potential contributing factors. This study will help those concerned with pharmacovigilance better understand the use and pitfalls of using spontaneous AE data. PMID:26109846

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bame, D.

To determine if seismic signals at frequencies up to 50 Hz are useful for detecting events and discriminating between earthquakes and explosions, approximately 180 events from the three-component high-frequency seismic element (HFSE) installed at the center of the Norwegian Regional Seismic Array (NRSA) have been analyzed. The attenuation of high-frequency signals in Scandinavia varies with distance, azimuth, magnitude, and source effects. Most of the events were detected with HFSE, although detections were better on the NRSA where signal processing techniques were used. Based on a preliminary analysis, high-frequency data do not appear to be a useful discriminant in Scandinavia. 21more » refs., 29 figs., 3 tabs.« less

Analysis of signal transduction in cell-free extracts and rafts of Xenopus eggs.

PubMed

Tokmakov, Alexander A; Iwasaki, Tetsushi; Sato, Ken-Ichi; Fukami, Yasuo

2010-05-01

Intracellular signaling during egg activation/fertilization has been extensively studied using intact eggs, which can be manipulated by microinjection of different mRNAs, proteins, or chemical drugs. Furthermore, egg extracts, which retain high CSF activity (CSF-arrested extracts), were developed for studying fertilization/activation signal transduction, which have significant advantages as a model system. The addition of calcium to CSF-arrested extracts initiates a plethora of signaling events that take place during egg activation. Hence, the signaling downstream of calcium mobilization has been successfully studied in the egg extracts. Moreover, despite disruption of membrane-associated signaling compartments and ordered compartmentalization during extract preparation, CSF-arrested extracts can be successfully used to study early signaling events, which occur upstream of calcium release during egg activation/fertilization. In combination with the CSF-arrested extracts, activated egg rafts can reproduce some events of egg activation, including PLCgamma activation, IP3 production, transient calcium release, MAPK inactivation, and meiotic exit. This becomes possible due to complementation of the sperm-induced egg activation signaling machinery present in the rafts with the components of signal transduction system localized in the extracts. Herein, we describe protocols for studying molecular mechanisms of egg fertilization/activation using cell-free extracts and membrane rafts prepared from metaphase-arrested Xenopus eggs.

Thrombotic events associated with C1 esterase inhibitor products in patients with hereditary angioedema: investigation from the United States Food and Drug Administration adverse event reporting system database.

PubMed

Gandhi, Pranav K; Gentry, William M; Bottorff, Michael B

2012-10-01

To investigate reports of thrombotic events associated with the use of C1 esterase inhibitor products in patients with hereditary angioedema in the United States. Retrospective data mining analysis. The United States Food and Drug Administration (FDA) adverse event reporting system (AERS) database. Case reports of C1 esterase inhibitor products, thrombotic events, and C1 esterase inhibitor product-associated thrombotic events (i.e., combination cases) were extracted from the AERS database, using the time frames of each respective product's FDA approval date through the second quarter of 2011. Bayesian statistical methodology within the neural network architecture was implemented to identify potential signals of a drug-associated adverse event. A potential signal is generated when the lower limit of the 95% 2-sided confidence interval of the information component, denoted by IC₀₂₅ , is greater than zero. This suggests that the particular drug-associated adverse event was reported to the database more often than statistically expected from reports available in the database. Ten combination cases of thrombotic events associated with the use of one C1 esterase inhibitor product (Cinryze) were identified in patients with hereditary angioedema. A potential signal demonstrated by an IC₀₂₅ value greater than zero (IC₀₂₅ = 2.91) was generated for these combination cases. The extracted cases from the AERS indicate continuing reports of thrombotic events associated with the use of one C1 esterase inhibitor product among patients with hereditary angioedema. The AERS is incapable of establishing a causal link and detecting the true frequency of an adverse event associated with a drug; however, potential signals of C1 esterase inhibitor product-associated thrombotic events among patients with hereditary angioedema were identified in the extracted combination cases. © 2012 Pharmacotherapy Publications, Inc.

Hippocampal neural correlates for values of experienced events.

PubMed

Lee, Hyunjung; Ghim, Jeong-Wook; Kim, Hoseok; Lee, Daeyeol; Jung, MinWhan

2012-10-24

Newly experienced events are often remembered together with how rewarding the experiences are personally. Although the hippocampus is a candidate structure where subjective values are integrated with other elements of episodic memory, it is uncertain whether and how the hippocampus processes value-related information. We examined how activity of dorsal CA1 and dorsal subicular neurons in rats performing a dynamic foraging task was related to reward values that were estimated using a reinforcement learning model. CA1 neurons carried significant signals related to action values before the animal revealed its choice behaviorally, indicating that the information on the expected values of potential choice outcomes was available in CA1. Moreover, after the outcome of the animal's goal choice was revealed, CA1 neurons carried robust signals for the value of chosen action and they temporally overlapped with the signals related to the animal's goal choice and its outcome, indicating that all the signals necessary to evaluate the outcome of an experienced event converged in CA1. On the other hand, value-related signals were substantially weaker in the subiculum. These results suggest a major role of CA1 in adding values to experienced events during episodic memory encoding. Given that CA1 neuronal activity is modulated by diverse attributes of an experienced event, CA1 might be a place where all the elements of episodic memory are integrated.

Glutathione Efflux and Cell Death

PubMed Central

2012-01-01

Abstract Significance: Glutathione (GSH) depletion is a central signaling event that regulates the activation of cell death pathways. GSH depletion is often taken as a marker of oxidative stress and thus, as a consequence of its antioxidant properties scavenging reactive species of both oxygen and nitrogen (ROS/RNS). Recent Advances: There is increasing evidence demonstrating that GSH loss is an active phenomenon regulating the redox signaling events modulating cell death activation and progression. Critical Issues: In this work, we review the role of GSH depletion by its efflux, as an important event regulating alterations in the cellular redox balance during cell death independent from oxidative stress and ROS/RNS formation. We discuss the mechanisms involved in GSH efflux during cell death progression and the redox signaling events by which GSH depletion regulates the activation of the cell death machinery. Future Directions: The evidence summarized here clearly places GSH transport as a central mechanism mediating redox signaling during cell death progression. Future studies should be directed toward identifying the molecular identity of GSH transporters mediating GSH extrusion during cell death, and addressing the lack of sensitive approaches to quantify GSH efflux. Antioxid. Redox Signal. 17, 1694–1713. PMID:22656858

Processing of the signals from the Liquid Xenon Calorimeter for timing measurements

NASA Astrophysics Data System (ADS)

Epshteyn, L. B.; Grebenuyk, A. A.; Kozyrev, A. N.; Logashenko, I. B.; Mikhaylov, K. Yu.; Ruban, A. A.; Yudin, Yu. V.

2017-02-01

One of the goals of the Cryogenic Magnetic Detector at Budker Institute of Nuclear Physics SB RAS (Novosibirsk, Russia) is a study of hadron production in electron-positron collisions near threshold. The neutron-antineutron pair production events can be detected only by the calorimeters. In the barrel calorimeter the antineutron annihilation typically occurs about 5 ns or later after the beams crossing. For identification of such events it is necessary to measure the time of flight of particles to the LXe-calorimeter with an accuracy of about a few nanoseconds. The LXe-calorimeter consists of 14 layers of ionization chambers with two readout: anode and cathode. The duration of charge collection to the anodes is about 4.5 μs, while the required accuracy of measuring of the signal arrival time is less than 1/1000 of that (i.e. 4.5 ns). Besides, the signals' shapes differ substantially from event to event, so the signal arrival time is measured in two stages. In the paper we describ the development of the special electronics which performs waveform digitization and the on-line measurement of signals' arrival times and amplitudes.

Prospects for distinguishing dark matter models using annual modulation

DOE PAGES

Witte, Samuel J.; Gluscevic, Vera; McDermott, Samuel D.

2017-02-24

It has recently been demonstrated that, in the event of a putative signal in dark matter direct detection experiments, properly identifying the underlying dark matter-nuclei interaction promises to be a challenging task. Given the most optimistic expectations for the number counts of recoil events in the forthcoming Generation 2 experiments, differentiating between interactions that produce distinct features in the recoil energy spectra will only be possible if a strong signal is observed simultaneously on a variety of complementary targets. However, there is a wide range of viable theories that give rise to virtually identical energy spectra, and may only differmore » by the dependence of the recoil rate on the dark matter velocity. In this work, we investigate how degeneracy between such competing models may be broken by analyzing the time dependence of nuclear recoils, i.e. the annual modulation of the rate. For this purpose, we simulate dark matter events for a variety of interactions and experiments, and perform a Bayesian model-selection analysis on all simulated data sets, evaluating the chance of correctly identifying the input model for a given experimental setup. Lastly, we find that including information on the annual modulation of the rate may significantly enhance the ability of a single target to distinguish dark matter models with nearly degenerate recoil spectra, but only with exposures beyond the expectations of Generation 2 experiments.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Witte, Samuel J.; Gluscevic, Vera; McDermott, Samuel D.

It has recently been demonstrated that, in the event of a putative signal in dark matter direct detection experiments, properly identifying the underlying dark matter-nuclei interaction promises to be a challenging task. Given the most optimistic expectations for the number counts of recoil events in the forthcoming Generation 2 experiments, differentiating between interactions that produce distinct features in the recoil energy spectra will only be possible if a strong signal is observed simultaneously on a variety of complementary targets. However, there is a wide range of viable theories that give rise to virtually identical energy spectra, and may only differmore » by the dependence of the recoil rate on the dark matter velocity. In this work, we investigate how degeneracy between such competing models may be broken by analyzing the time dependence of nuclear recoils, i.e. the annual modulation of the rate. For this purpose, we simulate dark matter events for a variety of interactions and experiments, and perform a Bayesian model-selection analysis on all simulated data sets, evaluating the chance of correctly identifying the input model for a given experimental setup. Lastly, we find that including information on the annual modulation of the rate may significantly enhance the ability of a single target to distinguish dark matter models with nearly degenerate recoil spectra, but only with exposures beyond the expectations of Generation 2 experiments.« less

Spatial extent of a hydrothermal system at Kilauea Volcano, Hawaii, determined from array analyses of shallow long-period seismicity 1. Method

USGS Publications Warehouse

Almendros, J.; Chouet, B.; Dawson, P.

2001-01-01

We present a probabilistic method to locate the source of seismic events using seismic antennas. The method is based on a comparison of the event azimuths and slownesses derived from frequency-slowness analyses of array data, with a slowness vector model. Several slowness vector models are considered including both homogeneous and horizontally layered half-spaces and also a more complex medium representing the actual topography and three-dimensional velocity structure of the region under study. In this latter model the slowness vector is obtained from frequency-slowness analyses of synthetic signals. These signals are generated using the finite difference method and include the effects of topography and velocity structure to reproduce as closely as possible the behavior of the observed wave fields. A comparison of these results with those obtained with a homogeneous half-space demonstrates the importance of structural and topographic effects, which, if ignored, lead to a bias in the source location. We use synthetic seismograms to test the accuracy and stability of the method and to investigate the effect of our choice of probability distributions. We conclude that this location method can provide the source position of shallow events within a complex volcanic structure such as Kilauea Volcano with an error of ??200 m. Copyright 2001 by the American Geophysical Union.

Alterations in tendon microenvironment in response to mechanical load: potential molecular targets for treatment strategies

PubMed Central

Fouda, Mohamed B; Thankam, Finosh G; Dilisio, Matthew F; Agrawal, Devendra K

2017-01-01

Rotator cuff (RC) tendons could beinflicted in many ways with an eventual outcome of pain, weakness and disability, which represent a large burden on health care cost. However, optimal healing, either conservatively or with surgical intervention, remains an issue that needs further investigation. Disorders of the RC tendons may result from external factors like trauma, or internal factors through physiologic and metabolic derangement. Most RC tendon disorders may be asymptomatic and may result from an over-activity of the inflicted shoulder and its tendons. Such tendon disorders are poorly diagnosed since patients do not seek medical attention until pain or weakness ensue. Immunological and biochemical events in RC disorders due to mechanical intolerance have not been investigated. Generally, the mechanical load drives normal physiological properties of the tendon. But, mechanical overload/burden exerts stress on tenocytes, and disrupts the tendon microenvironment by triggering a multitude of signaling pathways leading to extracellular matrix remodeling, disorganization, alteration in collagen composition and apoptosis. These events result in weak tendon which is highly susceptible to rupture or tear. In this article, we critically reviewed the intrinsic signaling pathways that are excessively triggered by continuous mechanical load and the counteracting physiological responses and associated derangements. The elucidation of the molecular events underlying mechanical stress-induced symptomatic/asymptomatic tendinopathy could provide information on potential target sites for translational application in the management of rotator cuff disorders. PMID:29118899

GDF5 PROGENITORS GIVE RISE TO FIBROCARTILAGE CELLS THAT MINERALIZE VIA HEDGEHOG SIGNALING TO FORM THE ZONAL ENTHESIS

PubMed Central

Dyment, Nathaniel A.; Breidenbach, Andrew P.; Schwartz, Andrea G.; Russell, Ryan P.; Aschbacher-Smith, Lindsey; Liu, Han; Hagiwara, Yusuke; Jiang, Rulang; Thomopoulos, Stavros; Butler, David L.; Rowe, David W.

2015-01-01

The sequence of events that leads to the formation of a functionally graded enthesis is not clearly defined. The current study demonstrates that clonal expansion of Gdf5 progenitors contributes to linear growth of the enthesis. Prior to mineralization, Col1+ cells in the enthesis appose Col2+ cells of the underlying primary cartilage. At the onset of enthesis mineralization, cells at the base of the enthesis express alkaline phosphatase, Indian hedgehog, and ColX as they mineralize. The mineralization front then extends towards the tendon midsubstance as cells above the front become encapsulated in mineralized fibrocartilage over time. The hedgehog (Hh) pathway regulates this process, as Hh-responsive Gli1+ cells within the developing enthesis mature from unmineralized to mineralized fibrochondrocytes in response to activated signaling. Hh signaling is required for mineralization, as tissue-specific deletion of its obligate transducer Smoothened in the developing tendon and enthesis cells leads to significant reductions in the apposition of mineralized fibrocartilage. Together, these findings provide a spatiotemporal map of events – from expansion of the embryonic progenitor pool to synthesis of the collagen template and finally mineralization of this template – that leads to the formation of the mature zonal enthesis. These results can inform future tendon-to-bone repair strategies to create a mechanically functional enthesis in which tendon collagen fibers are anchored to bone through mineralized fibrocartilage. PMID:26141957

Investigations of Periodic Disturbances on Seismic Aftershock Recordings

NASA Astrophysics Data System (ADS)

Liebsch, Mattes; Gorschlüter, Felix; Knoop, Jan-Frederik; Altmann, Jürgen

2013-04-01

The Comprehensive Nuclear Test-Ban Treaty Organisation (CTBTO) runs the International Monitoring System (IMS) to detect possible violations of the treaty. The seismic sensors of the IMS are set up to detect every underground explosion with a yield of 1 kT TNT equivalent or even better everywhere on the world. Under consideration of all IMS data the hypocentre of a large underground explosion is located within an area of about 1000 sq km. To verify if it was a violation of the Test-Ban Treaty the CTBTO (after CTBT entry into force) is allowed to carry out an on-site inspection (OSI) in the area of suspicion. During an OSI the hypocentre is to be located much more precisely; for this a local seismic aftershock monitoring system (SAMS) can be installed to detect small seismic events caused as a consequence of the explosion, such as relaxation of the rock around the cavity. However the magnitude of these aftershock signals is extremely weak. Other difficulties arise from other seismic signals in the inspection area, for example caused by vehicles of the inspectors, from coupling of airborne signals to the ground, or even by intended attempts to disturb the OSI. While the aftershock signals have a pulsed shape, man-made seismic signals (primarily created by engines) usually show periodic characteristics and thus are representable as a sum of sine functions and their harmonics. A mathematical expression for the Hann-windowed discrete Fourier transform of the underlying sine is used to characterise every such disturbance by the amplitude, frequency and phase. The contributions of these sines are computed and subtracted from the complex spectrum sequentially. Synthetic sines superposed to real signals, orders of magnitude stronger than the latter, can be removed successfully. Removal of periodic content from the signals of a helicopter overflight reduces the amplitude by a factor 3.3 when the frequencies are approximately constant. To reduce or prevent disturbing seismic signals created by coupling of acoustic waves to the ground in the first place a better understanding of the acoustic-seismic coupling is required. Several acoustic and seismic measurements of periodic signals (e.g. helicopters) and pulse-shaped signals (fire crackers, hammer blows) were analysed. The data were evaluated with respect to the distance between event and sensor, the elevation angle of the signal and the burying depth of the seismic sensors. From the correlation of acoustic and seismic spectral peaks the ratio of their spectral amplitudes can be calculated which gives the frequency dependent coupling coefficient. In the ongoing analysis the influence of constructive interference of surface waves, created by acoustic-seismic coupling at different positions in the vicinity of the sensor, is of special interest. Several recommendations for an OSI were developed with respect to sensor placement and flight trajectory of helicopters.

Using Pattern Recognition and Discriminance Analysis to Predict Critical Events in Large Signal Databases

NASA Astrophysics Data System (ADS)

Feller, Jens; Feller, Sebastian; Mauersberg, Bernhard; Mergenthaler, Wolfgang

2009-09-01

Many applications in plant management require close monitoring of equipment performance, in particular with the objective to prevent certain critical events. At each point in time, the information available to classify the criticality of the process, is represented through the historic signal database as well as the actual measurement. This paper presents an approach to detect and predict critical events, based on pattern recognition and discriminance analysis.

NASA EM Followup of LIGO-Virgo Candidate Events

NASA Technical Reports Server (NTRS)

Blackburn, Lindy L.

2011-01-01

We present a strategy for a follow-up of LIGO-Virgo candidate events using offline survey data from several NASA high-energy photon instruments aboard RXTE, Swift, and Fermi. Time and sky-location information provided by the GW trigger allows for a targeted search for prompt and afterglow EM signals. In doing so, we expect to be sensitive to signals which are too weak to be publicly reported as astrophysical EM events.

A non-orthogonal decomposition of flows into discrete events

NASA Astrophysics Data System (ADS)

Boxx, Isaac; Lewalle, Jacques

1998-11-01

This work is based on the formula for the inverse Hermitian wavelet transform. A signal can be interpreted as a (non-unique) superposition of near-singular, partially overlapping events arising from Dirac functions and/or its derivatives combined with diffusion.( No dynamics implied: dimensionless diffusion is related to the definition of the analyzing wavelets.) These events correspond to local maxima of spectral energy density. We successfully fitted model events of various orders on a succession of fields, ranging from elementary signals to one-dimensional hot-wire traces. We document edge effects, event overlap and its implications on the algorithm. The interpretation of the discrete singularities as flow events (such as coherent structures) and the fundamental non-uniqueness of the decomposition are discussed. The dynamics of these events will be examined in the companion paper.

Estimation of the displacements among distant events based on parallel tracking of events in seismic traces under uncertainty

NASA Astrophysics Data System (ADS)

Huamán Bustamante, Samuel G.; Cavalcanti Pacheco, Marco A.; Lazo Lazo, Juan G.

2018-07-01

The method we propose in this paper seeks to estimate interface displacements among strata related with reflection seismic events, in comparison to the interfaces at other reference points. To do so, we search for reflection events in the reference point of a second seismic trace taken from the same 3D survey and close to a well. However, the nature of the seismic data introduces uncertainty in the results. Therefore, we perform an uncertainty analysis using the standard deviation results from several experiments with cross-correlation of signals. To estimate the displacements of events in depth between two seismic traces, we create a synthetic seismic trace with an empirical wavelet and the sonic log of the well, close to the second seismic trace. Then, we relate the events of the seismic traces to the depth of the sonic log. Finally, we test the method with data from the Namorado Field in Brazil. The results show that the accuracy of the event estimated depth depends on the results of parallel cross-correlation, primarily those from the procedures used in the integration of seismic data with data from the well. The proposed approach can correctly identify several similar events in two seismic traces without requiring all seismic traces between two distant points of interest to correlate strata in the subsurface.

Premonitory acoustic emissions and stick-slip in natural and smooth-faulted Westerly granite

USGS Publications Warehouse

Thompson, B.D.; Young, R.P.; Lockner, David A.

2009-01-01

A stick-slip event was induced in a cylindrical sample of Westerly granite containing a preexisting natural fault by loading at constant confining pressure of 150 MPa. Continuously recorded acoustic emission (AE) data and computer tomography (CT)-generated images of the fault plane were combined to provide a detailed examination of microscale processes operating on the fault. The dynamic stick-slip event, considered to be a laboratory analog of an earthquake, generated an ultrasonic signal that was recorded as a large-amplitude AE event. First arrivals of this event were inverted to determine the nucleation site of slip, which is associated with a geometric asperity on the fault surface. CT images and AE locations suggest that a variety of asperities existed in the sample because of the intersection of branch or splay faults with the main fault. This experiment is compared with a stick-slip experiment on a sample prepared with a smooth, artificial saw-cut fault surface. Nearly a thousand times more AE were observed for the natural fault, which has a higher friction coefficient (0.78 compared to 0.53) and larger shear stress drop (140 compared to 68 MPa). However at the measured resolution, the ultrasonic signal emitted during slip initiation does not vary significantly between the two experiments, suggesting a similar dynamic rupture process. We propose that the natural faulted sample under triaxial compression provides a good laboratory analogue for a field-scale fault system in terms of the presence of asperities, fault surface heterogeneity, and interaction of branching faults. ?? 2009.

Gun muzzle flash detection using a CMOS single photon avalanche diode

NASA Astrophysics Data System (ADS)

Merhav, Tomer; Savuskan, Vitali; Nemirovsky, Yael

2013-10-01

Si based sensors, in particular CMOS Image sensors, have revolutionized low cost imaging systems but to date have hardly been considered as possible candidates for gun muzzle flash detection, due to performance limitations, and low SNR in the visible spectrum. In this study, a CMOS Single Photon Avalanche Diode (SPAD) module is used to record and sample muzzle flash events in the visible spectrum, from representative weapons, common on the modern battlefield. SPADs possess two crucial properties for muzzle flash imaging - Namely, very high photon detection sensitivity, coupled with a unique ability to convert the optical signal to a digital signal at the source pixel, thus practically eliminating readout noise. This enables high sampling frequencies in the kilohertz range without SNR degradation, in contrast to regular CMOS image sensors. To date, the SPAD has not been utilized for flash detection in an uncontrolled environment, such as gun muzzle flash detection. Gun propellant manufacturers use alkali salts to suppress secondary flashes ignited during the muzzle flash event. Common alkali salts are compounds based on Potassium or Sodium, with spectral emission lines around 769nm and 589nm, respectively. A narrow band filter around the Potassium emission doublet is used in this study to favor the muzzle flash signal over solar radiation. This research will demonstrate the SPAD's ability to accurately sample and reconstruct the temporal behavior of the muzzle flash in the visible wavelength under the specified imaging conditions. The reconstructed signal is clearly distinguishable from background clutter, through exploitation of flash temporal characteristics.

The expression of the β-defensins hBD-2 and hBD-3 is differentially regulated by NF-κB and MAPK/AP-1 pathways in an in vitro model of Candida esophagitis

PubMed Central

Steubesand, Nadine; Kiehne, Karlheinz; Brunke, Gabriele; Pahl, Rene; Reiss, Karina; Herzig, Karl-Heinz; Schubert, Sabine; Schreiber, Stefan; Fölsch, Ulrich R; Rosenstiel, Philip; Arlt, Alexander

2009-01-01

Background Candida albicans resides on epithelial surfaces as part of the physiological microflora. However, under certain conditions it may cause life-threatening infections like Candida sepsis. Human β-defensins (hBDs) are critical components of host defense at mucosal surfaces and we have recently shown that hBD-2 and hBD-3 are upregulated in Candida esophagitis. We therefore studied the role of Candidate signalling pathways in order to understand the mechanisms involved in regulation of hBD-expression by C. albicans. We used the esophageal cell line OE21 and analysed the role of paracrine signals from polymorphonuclear leukocytes (PMN) in an in vitro model of esophageal candidiasis. Results Supernatants of C. albicans or indirect coculture with C. albicans induces upregulation of hBD-2 and hBD-3 expression. PMNs strongly amplifies C. albicans-mediated induction of hBDs. By EMSA we demonstrate that C. albicans activates NF-κB and AP-1 in OE21 cells. Inhibition of these pathways revealed that hBD-2 expression is synergistically regulated by both NF-κB and AP-1. In contrast hBD-3 expression is independent of NF-κB and relies solely on an EGFR/MAPK/AP-1-dependent pathway. Conclusion Our analysis of signal transduction events demonstrate a functional interaction of epithelial cells with PMNs in response to Candida infection involving divergent signalling events that differentially govern hBD-2 and hBD-3 expression. PMID:19523197

Nitric oxide and phytohormone interactions: current status and perspectives

PubMed Central

Freschi, Luciano

2013-01-01

Nitric oxide (NO) is currently considered a ubiquitous signal in plant systems, playing significant roles in a wide range of responses to environmental and endogenous cues. During the signaling events leading to these plant responses, NO frequently interacts with plant hormones and other endogenous molecules, at times originating remarkably complex signaling cascades. Accumulating evidence indicates that virtually all major classes of plant hormones may influence, at least to some degree, the endogenous levels of NO. In addition, studies conducted during the induction of diverse plant responses have demonstrated that NO may also affect biosynthesis, catabolism/conjugation, transport, perception, and/or transduction of different phytohormones, such as auxins, gibberellins, cytokinins, abscisic acid, ethylene, salicylic acid, jasmonates, and brassinosteroids. Although still not completely elucidated, the mechanisms underlying the interaction between NO and plant hormones have recently been investigated in a number of species and plant responses. This review specifically focuses on the current knowledge of the mechanisms implicated in NO–phytohormone interactions during the regulation of developmental and metabolic plant events. The modifications triggered by NO on the transcription of genes encoding biosynthetic/degradative enzymes as well as proteins involved in the transport and signal transduction of distinct plant hormones will be contextualized during the control of developmental, metabolic, and defense responses in plants. Moreover, the direct post-translational modification of phytohormone biosynthetic enzymes and receptors through S-nitrosylation will also be discussed as a key mechanism for regulating plant physiological responses. Finally, some future perspectives toward a more complete understanding of NO–phytohormone interactions will also be presented and discussed. PMID:24130567

Prefrontal cholinergic mechanisms instigating shifts from monitoring for cues to cue-guided performance: Converging electrochemical and fMRI evidence from rats and humans

PubMed Central

Howe, William M.; Berry, Anne S.; Francois, Jennifer; Gilmour, Gary; Carp, Joshua M.; Tricklebank, Mark; Lustig, Cindy; Sarter, Martin

2013-01-01

We previously reported involvement of right prefrontal cholinergic activity in veridical signal detection. Here, we first recorded real-time acetylcholine release in prefrontal cortex during specific trial sequences in rats performing a task requiring signal detection as well as rejection of non-signal events. Cholinergic release events recorded with sub-second resolution (“transients”) were observed only during signal-hit trials, not during signal-miss trials or non-signal events. Moreover, cholinergic transients were not observed for consecutive hits; instead they were limited to signal-hit trials that were preceded by factual or perceived non-signal events (“incongruent hits”). This finding suggests that these transients mediate shifts from a state of perceptual attention, or monitoring for cues, to cue-evoked activation of response rules and the generation of a cue-directed response. Next, to determine the translational significance of the cognitive operations supporting incongruent hits we employed a version of the task previously validated for use in research in humans and BOLD-fMRI. Incongruent hits activated a region in the right rostral prefrontal cortex (BA 10). Furthermore, greater prefrontal activation was correlated with faster response times for incongruent hits. Finally, we measured tissue oxygen in rats, as a proxy for BOLD, and found prefrontal increases in oxygen levels solely during incongruent hits. These cross-species studies link a cholinergic response to a prefrontal BOLD activation and indicate that these interrelated mechanisms mediate the integration of external cues with internal representations to initiate and guide behavior. PMID:23678117

Towards Real-Time Detection of Gait Events on Different Terrains Using Time-Frequency Analysis and Peak Heuristics Algorithm.

PubMed

Zhou, Hui; Ji, Ning; Samuel, Oluwarotimi Williams; Cao, Yafei; Zhao, Zheyi; Chen, Shixiong; Li, Guanglin

2016-10-01

Real-time detection of gait events can be applied as a reliable input to control drop foot correction devices and lower-limb prostheses. Among the different sensors used to acquire the signals associated with walking for gait event detection, the accelerometer is considered as a preferable sensor due to its convenience of use, small size, low cost, reliability, and low power consumption. Based on the acceleration signals, different algorithms have been proposed to detect toe off (TO) and heel strike (HS) gait events in previous studies. While these algorithms could achieve a relatively reasonable performance in gait event detection, they suffer from limitations such as poor real-time performance and are less reliable in the cases of up stair and down stair terrains. In this study, a new algorithm is proposed to detect the gait events on three walking terrains in real-time based on the analysis of acceleration jerk signals with a time-frequency method to obtain gait parameters, and then the determination of the peaks of jerk signals using peak heuristics. The performance of the newly proposed algorithm was evaluated with eight healthy subjects when they were walking on level ground, up stairs, and down stairs. Our experimental results showed that the mean F1 scores of the proposed algorithm were above 0.98 for HS event detection and 0.95 for TO event detection on the three terrains. This indicates that the current algorithm would be robust and accurate for gait event detection on different terrains. Findings from the current study suggest that the proposed method may be a preferable option in some applications such as drop foot correction devices and leg prostheses.

Towards Real-Time Detection of Gait Events on Different Terrains Using Time-Frequency Analysis and Peak Heuristics Algorithm

PubMed Central

Zhou, Hui; Ji, Ning; Samuel, Oluwarotimi Williams; Cao, Yafei; Zhao, Zheyi; Chen, Shixiong; Li, Guanglin

2016-01-01

Real-time detection of gait events can be applied as a reliable input to control drop foot correction devices and lower-limb prostheses. Among the different sensors used to acquire the signals associated with walking for gait event detection, the accelerometer is considered as a preferable sensor due to its convenience of use, small size, low cost, reliability, and low power consumption. Based on the acceleration signals, different algorithms have been proposed to detect toe off (TO) and heel strike (HS) gait events in previous studies. While these algorithms could achieve a relatively reasonable performance in gait event detection, they suffer from limitations such as poor real-time performance and are less reliable in the cases of up stair and down stair terrains. In this study, a new algorithm is proposed to detect the gait events on three walking terrains in real-time based on the analysis of acceleration jerk signals with a time-frequency method to obtain gait parameters, and then the determination of the peaks of jerk signals using peak heuristics. The performance of the newly proposed algorithm was evaluated with eight healthy subjects when they were walking on level ground, up stairs, and down stairs. Our experimental results showed that the mean F1 scores of the proposed algorithm were above 0.98 for HS event detection and 0.95 for TO event detection on the three terrains. This indicates that the current algorithm would be robust and accurate for gait event detection on different terrains. Findings from the current study suggest that the proposed method may be a preferable option in some applications such as drop foot correction devices and leg prostheses. PMID:27706086

Competition between Visual Events Modulates the Influence of Salience during Free-Viewing of Naturalistic Videos

PubMed Central

Nardo, Davide; Console, Paola; Reverberi, Carlo; Macaluso, Emiliano

2016-01-01

In daily life the brain is exposed to a large amount of external signals that compete for processing resources. The attentional system can select relevant information based on many possible combinations of goal-directed and stimulus-driven control signals. Here, we investigate the behavioral and physiological effects of competition between distinctive visual events during free-viewing of naturalistic videos. Nineteen healthy subjects underwent functional magnetic resonance imaging (fMRI) while viewing short video-clips of everyday life situations, without any explicit goal-directed task. Each video contained either a single semantically-relevant event on the left or right side (Lat-trials), or multiple distinctive events in both hemifields (Multi-trials). For each video, we computed a salience index to quantify the lateralization bias due to stimulus-driven signals, and a gaze index (based on eye-tracking data) to quantify the efficacy of the stimuli in capturing attention to either side. Behaviorally, our results showed that stimulus-driven salience influenced spatial orienting only in presence of multiple competing events (Multi-trials). fMRI results showed that the processing of competing events engaged the ventral attention network, including the right temporoparietal junction (R TPJ) and the right inferior frontal cortex. Salience was found to modulate activity in the visual cortex, but only in the presence of competing events; while the orienting efficacy of Multi-trials affected activity in both the visual cortex and posterior parietal cortex (PPC). We conclude that in presence of multiple competing events, the ventral attention system detects semantically-relevant events, while regions of the dorsal system make use of saliency signals to select relevant locations and guide spatial orienting. PMID:27445760

Detection and analysis of a transient energy burst with beamforming of multiple teleseismic phases

NASA Astrophysics Data System (ADS)

Retailleau, Lise; Landès, Matthieu; Gualtieri, Lucia; Shapiro, Nikolai M.; Campillo, Michel; Roux, Philippe; Guilbert, Jocelyn

2018-01-01

Seismological detection methods are traditionally based on picking techniques. These methods cannot be used to analyse emergent signals where the arrivals cannot be picked. Here, we detect and locate seismic events by applying a beamforming method that combines multiple body-wave phases to USArray data. This method explores the consistency and characteristic behaviour of teleseismic body waves that are recorded by a large-scale, still dense, seismic network. We perform time-slowness analysis of the signals and correlate this with the time-slowness equivalent of the different body-wave phases predicted by a global traveltime calculator, to determine the occurrence of an event with no a priori information about it. We apply this method continuously to one year of data to analyse the different events that generate signals reaching the USArray network. In particular, we analyse in detail a low-frequency secondary microseismic event that occurred on 2010 February 1. This event, that lasted 1 d, has a narrow frequency band around 0.1 Hz, and it occurred at a distance of 150° to the USArray network, South of Australia. We show that the most energetic phase observed is the PKPab phase. Direct amplitude analysis of regional seismograms confirms the occurrence of this event. We compare the seismic observations with models of the spectral density of the pressure field generated by the interferences between oceanic waves. We attribute the observed signals to a storm-generated microseismic event that occurred along the South East Indian Ridge.

Gait Event Detection in Real-World Environment for Long-Term Applications: Incorporating Domain Knowledge Into Time-Frequency Analysis.

PubMed

Khandelwal, Siddhartha; Wickstrom, Nicholas

2016-12-01

Detecting gait events is the key to many gait analysis applications that would benefit from continuous monitoring or long-term analysis. Most gait event detection algorithms using wearable sensors that offer a potential for use in daily living have been developed from data collected in controlled indoor experiments. However, for real-word applications, it is essential that the analysis is carried out in humans' natural environment; that involves different gait speeds, changing walking terrains, varying surface inclinations and regular turns among other factors. Existing domain knowledge in the form of principles or underlying fundamental gait relationships can be utilized to drive and support the data analysis in order to develop robust algorithms that can tackle real-world challenges in gait analysis. This paper presents a novel approach that exhibits how domain knowledge about human gait can be incorporated into time-frequency analysis to detect gait events from long-term accelerometer signals. The accuracy and robustness of the proposed algorithm are validated by experiments done in indoor and outdoor environments with approximately 93 600 gait events in total. The proposed algorithm exhibits consistently high performance scores across all datasets in both, indoor and outdoor environments.

Signal detection of adverse events with imperfect confirmation rates in vaccine safety studies using self-controlled case series design.

PubMed

Xu, Stanley; Newcomer, Sophia; Nelson, Jennifer; Qian, Lei; McClure, David; Pan, Yi; Zeng, Chan; Glanz, Jason

2014-05-01

The Vaccine Safety Datalink project captures electronic health record data including vaccinations and medically attended adverse events on 8.8 million enrollees annually from participating managed care organizations in the United States. While the automated vaccination data are generally of high quality, a presumptive adverse event based on diagnosis codes in automated health care data may not be true (misclassification). Consequently, analyses using automated health care data can generate false positive results, where an association between the vaccine and outcome is incorrectly identified, as well as false negative findings, where a true association or signal is missed. We developed novel conditional Poisson regression models and fixed effects models that accommodate misclassification of adverse event outcome for self-controlled case series design. We conducted simulation studies to evaluate their performance in signal detection in vaccine safety hypotheses generating (screening) studies. We also reanalyzed four previously identified signals in a recent vaccine safety study using the newly proposed models. Our simulation studies demonstrated that (i) outcome misclassification resulted in both false positive and false negative signals in screening studies; (ii) the newly proposed models reduced both the rates of false positive and false negative signals. In reanalyses of four previously identified signals using the novel statistical models, the incidence rate ratio estimates and statistical significances were similar to those using conventional models and including only medical record review confirmed cases. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles

PubMed Central

Leitz, Jeremy; Kavalali, Ege T

2014-01-01

Presynaptic terminals release neurotransmitters spontaneously in a manner that can be regulated by Ca2+. However, the mechanisms underlying this regulation are poorly understood because the inherent stochasticity and low probability of spontaneous fusion events has curtailed their visualization at individual release sites. Here, using pH-sensitive optical probes targeted to synaptic vesicles, we visualized single spontaneous fusion events and found that they are retrieved extremely rapidly with faster re-acidification kinetics than their action potential-evoked counterparts. These fusion events were coupled to postsynaptic NMDA receptor-driven Ca2+ signals, and at elevated Ca2+ concentrations there was an increase in the number of vesicles that would undergo fusion. Furthermore, spontaneous vesicle fusion propensity in a synapse was Ca2+-dependent but regulated autonomously: independent of evoked fusion probability at the same synapse. Taken together, these results expand classical quantal analysis to incorporate endocytic and exocytic phases of single fusion events and uncover autonomous regulation of spontaneous fusion. DOI: http://dx.doi.org/10.7554/eLife.03658.001 PMID:25415052

High-luminosity primary vertex selection in top-quark studies using the Collider Detector at Fermilab

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buzatu, Adrian; /McGill U.

2006-08-01

Improving our ability to identify the top quark pair (t{bar t}) primary vertex (PV) on an event-by-event basis is essential for many analyses in the lepton-plus-jets channel performed by the Collider Detector at Fermilab (CDF) Collaboration. We compare the algorithm currently used by CDF (A1) with another algorithm (A2) using Monte Carlo simulation at high instantaneous luminosities. We confirm that A1 is more efficient than A2 at selecting the t{bar t} PV at all PV multiplicities, both with efficiencies larger than 99%. Event selection rejects events with a distance larger than 5 cm along the proton beam between the t{barmore » t} PV and the charged lepton. We find flat distributions for the signal over background significance of this cut for all cut values larger than 1 cm, for all PV multiplicities and for both algorithms. We conclude that any cut value larger than 1 cm is acceptable for both algorithms under the Tevatron's expected instantaneous luminosity improvements.« less

Engineering self-contained DNA circuit for proximity recognition and localized signal amplification of target biomolecules

PubMed Central

Ang, Yan Shan; Yung, Lin-Yue Lanry

2014-01-01

Biomolecular interactions have important cellular implications, however, a simple method for the sensing of such proximal events is lacking in the current molecular toolbox. We designed a dynamic DNA circuit capable of recognizing targets in close proximity to initiate a pre-programmed signal transduction process resulting in localized signal amplification. The entire circuit was engineered to be self-contained, i.e. it can self-assemble onto individual target molecules autonomously and form localized signal with minimal cross-talk. α-thrombin was used as a model protein to evaluate the performance of the individual modules and the overall circuit for proximity interaction under physiologically relevant buffer condition. The circuit achieved good selectivity in presence of non-specific protein and interfering serum matrix and successfully detected for physiologically relevant α-thrombin concentration (50 nM–5 μM) in a single mixing step without any further washing. The formation of localized signal at the interaction site can be enhanced kinetically through the control of temperature and probe concentration. This work provides a basic general framework from which other circuit modules can be adapted for the sensing of other biomolecular or cellular interaction of interest. PMID:25056307

Phospholipase D Signaling Pathways and Phosphatidic Acid as Therapeutic Targets in Cancer

PubMed Central

Bruntz, Ronald C.; Lindsley, Craig W.

2014-01-01

Phospholipase D is a ubiquitous class of enzymes that generates phosphatidic acid as an intracellular signaling species. The phospholipase D superfamily plays a central role in a variety of functions in prokaryotes, viruses, yeast, fungi, plants, and eukaryotic species. In mammalian cells, the pathways modulating catalytic activity involve a variety of cellular signaling components, including G protein–coupled receptors, receptor tyrosine kinases, polyphosphatidylinositol lipids, Ras/Rho/ADP-ribosylation factor GTPases, and conventional isoforms of protein kinase C, among others. Recent findings have shown that phosphatidic acid generated by phospholipase D plays roles in numerous essential cellular functions, such as vesicular trafficking, exocytosis, autophagy, regulation of cellular metabolism, and tumorigenesis. Many of these cellular events are modulated by the actions of phosphatidic acid, and identification of two targets (mammalian target of rapamycin and Akt kinase) has especially highlighted a role for phospholipase D in the regulation of cellular metabolism. Phospholipase D is a regulator of intercellular signaling and metabolic pathways, particularly in cells that are under stress conditions. This review provides a comprehensive overview of the regulation of phospholipase D activity and its modulation of cellular signaling pathways and functions. PMID:25244928

Phospholipase D signaling pathways and phosphatidic acid as therapeutic targets in cancer.

PubMed

Bruntz, Ronald C; Lindsley, Craig W; Brown, H Alex

2014-10-01

Phospholipase D is a ubiquitous class of enzymes that generates phosphatidic acid as an intracellular signaling species. The phospholipase D superfamily plays a central role in a variety of functions in prokaryotes, viruses, yeast, fungi, plants, and eukaryotic species. In mammalian cells, the pathways modulating catalytic activity involve a variety of cellular signaling components, including G protein-coupled receptors, receptor tyrosine kinases, polyphosphatidylinositol lipids, Ras/Rho/ADP-ribosylation factor GTPases, and conventional isoforms of protein kinase C, among others. Recent findings have shown that phosphatidic acid generated by phospholipase D plays roles in numerous essential cellular functions, such as vesicular trafficking, exocytosis, autophagy, regulation of cellular metabolism, and tumorigenesis. Many of these cellular events are modulated by the actions of phosphatidic acid, and identification of two targets (mammalian target of rapamycin and Akt kinase) has especially highlighted a role for phospholipase D in the regulation of cellular metabolism. Phospholipase D is a regulator of intercellular signaling and metabolic pathways, particularly in cells that are under stress conditions. This review provides a comprehensive overview of the regulation of phospholipase D activity and its modulation of cellular signaling pathways and functions. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

A Distributed Compressive Sensing Scheme for Event Capture in Wireless Visual Sensor Networks

NASA Astrophysics Data System (ADS)

Hou, Meng; Xu, Sen; Wu, Weiling; Lin, Fei

2018-01-01

Image signals which acquired by wireless visual sensor network can be used for specific event capture. This event capture is realized by image processing at the sink node. A distributed compressive sensing scheme is used for the transmission of these image signals from the camera nodes to the sink node. A measurement and joint reconstruction algorithm for these image signals are proposed in this paper. Make advantage of spatial correlation between images within a sensing area, the cluster head node which as the image decoder can accurately co-reconstruct these image signals. The subjective visual quality and the reconstruction error rate are used for the evaluation of reconstructed image quality. Simulation results show that the joint reconstruction algorithm achieves higher image quality at the same image compressive rate than the independent reconstruction algorithm.

Spectral entropy analysis of the respiratory signal and its relationship with the cyclic alternating pattern during sleep

NASA Astrophysics Data System (ADS)

Reyes-Sanchez, E.; Alba, A.; Méndez, M. O.; Milioli, G.; Parrino, L.

2016-07-01

A-phases consist of transient cortical events that normally occur during NREM sleep and can be observed directly in the EEG signals. One particular kind of A-phases, namely, A3-phases are related to arousals from sleep during which increased activity in other systems (such as the cardiovascular and respiratory systems) can also be observed. This study aims to characterize disruptions in the oscillations of the airflow signal during A3-phases of sleep. Spectral entropy was used to quantify the bandwidth of the airflow signal, which under baseline conditions (prior to an A3-phase) resembles a sinusoidal wave with a frequency of about 0.25 Hz and has low spectral entropy values. It was found that during most A3-phases the spectral entropy increases significantly in 70% of the test subjects. These changes occur with higher probability during A3-phases that are longer than 10s, suggesting a delay between the onset of an A3-phase and the effect it has on the respiratory system.

Diet and cognition: interplay between cell metabolism and neuronal plasticity.

PubMed

Gomez-Pinilla, Fernando; Tyagi, Ethika

2013-11-01

To discuss studies in humans and animals revealing the ability of foods to benefit the brain: new information with regards to mechanisms of action and the treatment of neurological and psychiatric disorders. Dietary factors exert their effects on the brain by affecting molecular events related to the management of energy metabolism and synaptic plasticity. Energy metabolism influences neuronal function, neuronal signaling, and synaptic plasticity, ultimately affecting mental health. Epigenetic regulation of neuronal plasticity appears as an important mechanism by which foods can prolong their effects on long-term neuronal plasticity. The prime focus of the discussion is to emphasize the role of cell metabolism as a mediator for the action of foods on the brain. Oxidative stress promotes damage to phospholipids present in the plasma membrane such as the omega-3 fatty acid docosahexenoic acid, disrupting neuronal signaling. Thus, dietary docosahexenoic acid seems crucial for supporting plasma membrane function, interneuronal signaling, and cognition. The dual action of brain-derived neurotrophic factor in neuronal metabolism and synaptic plasticity is crucial for activating signaling cascades under the action of diet and other environmental factors, using mechanisms of epigenetic regulation.

Climate Signals: An On-Line Digital Platform for Mapping Climate Change Impacts in Real Time

NASA Astrophysics Data System (ADS)

Cutting, H.

2016-12-01

Climate Signals is an on-line digital platform for cataloging and mapping the impacts of climate change. The CS platform specifies and details the chains of connections between greenhouse gas emissions and individual climate events. Currently in open-beta release, the platform is designed to to engage and serve the general public, news media, and policy-makers, particularly in real-time during extreme climate events. Climate Signals consists of a curated relational database of events and their links to climate change, a mapping engine, and a gallery of climate change monitors offering real-time data. For each event in the database, an infographic engine provides a custom attribution "tree" that illustrates the connections to climate change. In addition, links to key contextual resources are aggregated and curated for each event. All event records are fully annotated with detailed source citations and corresponding hyper links. The system of attribution used to link events to climate change in real-time is detailed here. This open-beta release is offered for public user testing and engagement. Launched in May 2016, the operation of this platform offers lessons for public engagement in climate change impacts.

Elevated Carbon Dioxide Concentration Reduces Alarm Signaling in Aphids.

PubMed

Boullis, Antoine; Fassotte, Bérénice; Sarles, Landry; Lognay, Georges; Heuskin, Stéphanie; Vanderplanck, Maryse; Bartram, Stefan; Haubruge, Eric; Francis, Frédéric; Verheggen, François J

2017-02-01

Insects often rely on olfaction to communicate with conspecifics. While the chemical language of insects has been deciphered in recent decades, few studies have assessed how changes in atmospheric greenhouse gas concentrations might impact pheromonal communication in insects. Here, we hypothesize that changes in the concentration of atmospheric carbon dioxide affect the whole dynamics of alarm signaling in aphids, including: (1) the production of the active compound (E)-β-farnesene (Eβf), (2) emission behavior when under attack, (3) perception by the olfactory apparatus, and (4) the escape response. We reared two strains of the pea aphid, Acyrthosiphon pisum, under ambient and elevated CO 2 concentrations over several generations. We found that an increase in CO 2 concentration reduced the production (i.e., individual content) and emission (released under predation events) of Eβf. While no difference in Eβf neuronal perception was observed, we found that an increase in CO 2 strongly reduced the escape behavior expressed by an aphid colony following exposure to natural doses of alarm pheromone. In conclusion, our results confirm that changes to greenhouse gases impact chemical communication in the pea aphid, and could potentially have a cascade effect on interactions with higher trophic levels.

Search for Neutrinos in Super-Kamiokande Associated with the GW170817 Neutron-star Merger

NASA Astrophysics Data System (ADS)

Abe, K.; Bronner, C.; Hayato, Y.; Ikeda, M.; Iyogi, K.; Kameda, J.; Kato, Y.; Kishimoto, Y.; Marti, Ll.; Miura, M.; Moriyama, S.; Nakahata, M.; Nakajima, Y.; Nakano, Y.; Nakayama, S.; Orii, A.; Pronost, G.; Sekiya, H.; Shiozawa, M.; Sonoda, Y.; Takeda, A.; Takenaka, A.; Tanaka, H.; Tasaka, S.; Yano, T.; Akutsu, R.; Kajita, T.; Nishimura, Y.; Okumura, K.; Tsui, K. M.; Labarga, L.; Fernandez, P.; Blaszczyk, F. d. M.; Kachulis, C.; Kearns, E.; Raaf, J. L.; Stone, J. L.; Sulak, L. R.; Berkman, S.; Tobayama, S.; Bian, J.; Elnimr, M.; Kropp, W. R.; Locke, S.; Mine, S.; Weatherly, P.; Smy, M. B.; Sobel, H. W.; Takhistov, V.; Ganezer, K. S.; Hill, J.; Kim, J. Y.; Lim, I. T.; Park, R. G.; Li, Z.; O’Sullivan, E.; Scholberg, K.; Walter, C. W.; Gonin, M.; Imber, J.; Mueller, Th. A.; Ishizuka, T.; Nakamura, T.; Jang, J. S.; Choi, K.; Learned, J. G.; Matsuno, S.; Amey, J.; Litchfield, R. P.; Ma, W. Y.; Uchida, Y.; Wascko, M. O.; Catanesi, M. G.; Intonti, R. A.; Radicioni, E.; De Rosa, G.; Ali, A.; Collazuol, G.; Ludovici, L.; Cao, S.; Friend, M.; Hasegawa, T.; Ishida, T.; Ishii, T.; Kobayashi, T.; Nakadaira, T.; Nakamura, K.; Oyama, Y.; Sakashita, K.; Sekiguchi, T.; Tsukamoto, T.; Abe, KE.; Hasegawa, M.; Suzuki, A. T.; Takeuchi, Y.; Hayashino, T.; Hirota, S.; Jiang, M.; Mori, M.; Nakamura, KE.; Nakaya, T.; Wendell, R. A.; Anthony, L. H. V.; McCauley, N.; Pritchard, A.; Fukuda, Y.; Itow, Y.; Murase, M.; Muto, F.; Mijakowski, P.; Frankiewicz, K.; Jung, C. K.; Li, X.; Palomino, J. L.; Santucci, G.; Viela, C.; Wilking, M. J.; Yanagisawa, C.; Fukuda, D.; Ishino, H.; Ito, S.; Kibayashi, A.; Koshio, Y.; Nagata, H.; Sakuda, M.; Xu, C.; Kuno, Y.; Wark, D.; Di Lodovico, F.; Richards, B.; Molina Sedgwick, S.; Tacik, R.; Kim, S. B.; Cole, A.; Thompson, L.; Okazawa, H.; Choi, Y.; Ito, K.; Nishijima, K.; Koshiba, M.; Suda, Y.; Yokoyama, M.; Calland, R. G.; Hartz, M.; Martens, K.; Murdoch, M.; Quilain, B.; Simpson, C.; Suzuki, Y.; Vagins, M. R.; Hamabe, D.; Kuze, M.; Okajima, Y.; Yoshida, T.; Ishitsuka, M.; Martin, J. F.; Nantais, C. M.; Tanaka, H. A.; Towstego, T.; Konaka, A.; Chen, S.; Wan, L.; Minamino, A.; The Super-Kamiokande Collaboration

2018-04-01

We report the results of a neutrino search in Super-Kamiokande (SK) for coincident signals with the first detected gravitational wave (GW) produced by a binary neutron-star merger, GW170817, which was followed by a short gamma-ray burst, GRB170817A, and a kilonova/macronova. We searched for coincident neutrino events in the range from 3.5 MeV to ∼100 PeV, in a time window ±500 s around the gravitational wave detection time, as well as during a 14-day period after the detection. No significant neutrino signal was observed for either time window. We calculated 90% confidence level upper limits on the neutrino fluence for GW170817. From the upward-going-muon events in the energy region above 1.6 GeV, the neutrino fluence limit is {16.0}-0.6+0.7 ({21.3}-0.8+1.1) cm‑2 for muon neutrinos (muon antineutrinos), with an error range of ±5° around the zenith angle of NGC4993, and the energy spectrum is under the assumption of an index of ‑2. The fluence limit for neutrino energies less than 100 MeV, for which the emission mechanism would be different than for higher-energy neutrinos, is also calculated. It is 6.6 × 107 cm‑2 for anti-electron neutrinos under the assumption of a Fermi–Dirac spectrum with average energy of 20 MeV.

The grapevine guard cell-related VvMYB60 transcription factor is involved in the regulation of stomatal activity and is differentially expressed in response to ABA and osmotic stress

PubMed Central

2011-01-01

Background Under drought, plants accumulate the signaling hormone abscisic acid (ABA), which induces the rapid closure of stomatal pores to prevent water loss. This event is trigged by a series of signals produced inside guard cells which finally reduce their turgor. Many of these events are tightly regulated at the transcriptional level, including the control exerted by MYB proteins. In a previous study, while identifying the grapevine R2R3 MYB family, two closely related genes, VvMYB30 and VvMYB60 were found with high similarity to AtMYB60, an Arabidopsis guard cell-related drought responsive gene. Results Promoter-GUS transcriptional fusion assays showed that expression of VvMYB60 was restricted to stomatal guard cells and was attenuated in response to ABA. Unlike VvMYB30, VvMYB60 was able to complement the loss-of-function atmyb60-1 mutant, indicating that VvMYB60 is the only true ortholog of AtMYB60 in the grape genome. In addition, VvMYB60 was differentially regulated during development of grape organs and in response to ABA and drought-related stress conditions. Conclusions These results show that VvMYB60 modulates physiological responses in guard cells, leading to the possibility of engineering stomatal conductance in grapevine, reducing water loss and helping this species to tolerate drought under extreme climatic conditions. PMID:22018045

Decision support methods for the detection of adverse events in post-marketing data.

PubMed

Hauben, M; Bate, A

2009-04-01

Spontaneous reporting is a crucial component of post-marketing drug safety surveillance despite its significant limitations. The size and complexity of some spontaneous reporting system databases represent a challenge for drug safety professionals who traditionally have relied heavily on the scientific and clinical acumen of the prepared mind. Computer algorithms that calculate statistical measures of reporting frequency for huge numbers of drug-event combinations are increasingly used to support pharamcovigilance analysts screening large spontaneous reporting system databases. After an overview of pharmacovigilance and spontaneous reporting systems, we discuss the theory and application of contemporary computer algorithms in regular use, those under development, and the practical considerations involved in the implementation of computer algorithms within a comprehensive and holistic drug safety signal detection program.

Vasopressin excites interneurons to suppress hippocampal network activity across a broad span of brain maturity at birth

PubMed Central

Spoljaric, Albert; Seja, Patricia; Spoljaric, Inkeri; Virtanen, Mari A.; Lindfors, Jenna; Uvarov, Pavel; Summanen, Milla; Crow, Ailey K.; Hsueh, Brian; Puskarjov, Martin; Ruusuvuori, Eva; Voipio, Juha; Deisseroth, Karl; Kaila, Kai

2017-01-01

During birth in mammals, a pronounced surge of fetal peripheral stress hormones takes place to promote survival in the transition to the extrauterine environment. However, it is not known whether the hormonal signaling involves central pathways with direct protective effects on the perinatal brain. Here, we show that arginine vasopressin specifically activates interneurons to suppress spontaneous network events in the perinatal hippocampus. Experiments done on the altricial rat and precocial guinea pig neonate demonstrated that the effect of vasopressin is not dependent on the level of maturation (depolarizing vs. hyperpolarizing) of postsynaptic GABAA receptor actions. Thus, the fetal mammalian brain is equipped with an evolutionarily conserved mechanism well-suited to suppress energetically expensive correlated network events under conditions of reduced oxygen supply at birth. PMID:29183979

Advances in Electrophysiological Research

PubMed Central

Kamarajan, Chella; Porjesz, Bernice

2015-01-01

Electrophysiological measures of brain function are effective tools to understand neurocognitive phenomena and sensitive indicators of pathophysiological processes associated with various clinical conditions, including alcoholism. Individuals with alcohol use disorder (AUD) and their high-risk offspring have consistently shown dysfunction in several electrophysiological measures in resting state (i.e., electroencephalogram) and during cognitive tasks (i.e., event-related potentials and event-related oscillations). Researchers have recently developed sophisticated signal-processing techniques to characterize different aspects of brain dynamics, which can aid in identifying the neural mechanisms underlying alcoholism and other related complex disorders. These quantitative measures of brain function also have been successfully used as endophenotypes to identify and help understand genes associated with AUD and related disorders. Translational research also is examining how brain electrophysiological measures potentially can be applied to diagnosis, prevention, and treatment. PMID:26259089

Exploring the Potential Routine Use of Electronic Healthcare Record Data to Strengthen Early Signal Assessment in UK Medicines Regulation: Proof-of-Concept Study.

PubMed

Donegan, Katherine; Owen, Rebecca; Bird, Helena; Burch, Brian; Smith, Alex; Tregunno, Phil

2018-05-03

Electronic healthcare record (EHR) databases are used within pharmacoepidemiology studies to confirm or refute safety signals arising from spontaneous adverse event reports. However, there has been limited routine use of such data earlier in the signal management process, to help rapidly contextualise signals and strengthen preliminary assessment or to inform decisions regarding action including the need for further studies. This study explores the value of EHR used in this way within a regulatory environment via an automated analysis platform. Safety signals raised at the UK Medicines and Healthcare products Regulatory Agency (MHRA) between July 2014 and June 2015 were individually reviewed by a multi-disciplinary team. They assessed the feasibility of identifying the exposure and event of interest using primary care data from the Clinical Practice Research Datalink (CPRD) within the Commonwealth Vigilance Workbench (CVW) Longitudinal Module platform, which was designed to facilitate routine descriptive analysis of signals using EHR. Three signals, where exposure and event could be well identified, were retrospectively analysed using the platform. Of 69 unique new signals, 20 were for drugs prescribed predominately in secondary care or available without prescription, which would not be identified in primary care. A further 17 were brand, formulation, or dose-specific issues, were related to mortality, were relevant only to a subgroup of patients, or were drug interactions, and hence could not be reviewed using the platform given its limitations. Analyses of exposure and incidence of the adverse event could be produced using CPRD within the CMV Longitudinal Module for 32 (46%) signals. The case studies demonstrated that the data provided supporting evidence for confirming initial assessment of the signal and deciding upon the need for further action. CPRD can routinely provide useful early insights into clinical context when assessing a large proportion of safety signals within a regulatory environment provided that a flexible approach is adopted within the analysis platform.

Cryogenic gaseous photomultipliers and liquid hole- multipliers: advances in THGEM-based sensors for future noble-liquid TPCs

NASA Astrophysics Data System (ADS)

Arazi, L.; Coimbra, A. E. C.; Erdal, E.; Israelashvili, I.; Rappaport, M. L.; Shchemelinin, S.; Vartsky, D.; dos Santos, J. M. F.; A, Breskin

2015-11-01

Dual-phase noble-liquid TPCs are presently the most sensitive instruments for direct dark matter detection. Scaling up existing ton-scale designs to the multi-ton regime may prove to be technologically challenging. This includes both large-area coverage with affordable high-QE UV-photon detectors, and maintaining high precision in measuring the charge and light signals of rare events with keV-scale energy depositions. We present our recent advances in two complementary approaches to these problems: large-area cryogenic gaseous photomultipliers (GPM) for UV-photon detection, and liquid-hole multipliers (LHM) that provide electroluminescence light in response to ionization electrons and primary scintillation photons, using perforated electrodes immersed within the noble liquid. Results from a 10 cm diameter GPM coupled to a dual-phase liquid- xenon TPC demonstrate the feasibility of recording - for the first time - both primary (“S1”) and secondary (“S2”) scintillation signals, over a very broad dynamic range. The detector, comprising a triple-THGEM structure with CsI on the first element, has been operating stably at 180 K with gains larger than 105; it provided high single-photon detection efficiency - in the presence of massive alpha-particle induced S2 signals; S1 scintillation signals were recorded with time resolutions of 1.2 ns (RMS). Results with the LHM operated in liquid xenon yielded large photon gains, with a pulse-height resolution of 11% (RMS) for alpha-particle induced S2 signals. The detector response was stable over several months. The response of the S2 signals to rapid changes in pressure lead to the conclusion that the underlying mechanism for S2 light is electroluminescence in xenon bubbles trapped below the immersed THGEM electrode. Both studies have the potential of paving the way towards new designs of dual- and single-phase noble-liquid TPCs that could simplify the conception of future multi-ton detectors of dark matter and other rare events.

Structural Basis for Nucleotide Exchange in Heterotrimeric G Proteins

PubMed Central

Dror, Ron O.; Mildorf, Thomas J.; Hilger, Daniel; Manglik, Aashish; Borhani, David W.; Arlow, Daniel H.; Philippsen, Ansgar; Villanueva, Nicolas; Yang, Zhongyu; Lerch, Michael T.; Hubbell, Wayne L.; Kobilka, Brian K.; Sunahara, Roger K.; Shaw, David E.

2016-01-01

G protein–coupled receptors (GPCRs) relay diverse extracellular signals into cells by catalyzing nucleotide release from heterotrimeric G proteins, but the mechanism underlying this quintessential molecular signaling event has remained unclear. Here we use atomic-level simulations to elucidate the nucleotide-release mechanism. We find that the G protein α subunit Ras and helical domains—previously observed to separate widely upon receptor binding to expose the nucleotide-binding site—separate spontaneously and frequently even in the absence of a receptor. Domain separation is necessary but not sufficient for rapid nucleotide release. Rather, receptors catalyze nucleotide release by favoring an internal structural rearrangement of the Ras domain that weakens its nucleotide affinity. We use double electron-electron resonance spectroscopy and protein engineering to confirm predictions of our computationally determined mechanism. PMID:26089515

Dark Matter "Collider" from Inelastic Boosted Dark Matter.

PubMed

Kim, Doojin; Park, Jong-Chul; Shin, Seodong

2017-10-20

We propose a novel dark matter (DM) detection strategy for models with a nonminimal dark sector. The main ingredients in the underlying DM scenario are a boosted DM particle and a heavier dark sector state. The relativistic DM impinged on target material scatters off inelastically to the heavier state, which subsequently decays into DM along with lighter states including visible (standard model) particles. The expected signal event, therefore, accompanies a visible signature by the secondary cascade process associated with a recoiling of the target particle, differing from the typical neutrino signal not involving the secondary signature. We then discuss various kinematic features followed by DM detection prospects at large-volume neutrino detectors with a model framework where a dark gauge boson is the mediator between the standard model particles and DM.

Targeting PYK2 mediates microenvironment-specific cell death in multiple myeloma

PubMed Central

Meads, MB; Fang, B; Mathews, L; Gemmer, J; Nong, L; Rosado-Lopez, I; Nguyen, T; Ring, JE; Matsui, W; MacLeod, AR; Pachter, JA; Hazlehurst, LA; Koomen, JM; Shain, KH

2015-01-01

Multiple myeloma (MM) remains an incurable malignancy due, in part, to the influence of the bone marrow microenvironment on survival and drug response. Identification of microenvironment-specific survival signaling determinants is critical for the rational design of therapy and elimination of MM. Previously, we have shown that collaborative signaling between β1 integrin-mediated adhesion to fibronectin and interleukin-6 confers a more malignant phenotype via amplification of signal transducer and activator of transcription 3 (STAT3) activation. Further characterization of the events modulated under these conditions with quantitative phosphotyrosine profiling identified 193 differentially phosphorylated peptides. Seventy-seven phosphorylations were upregulated upon adhesion, including PYK2/FAK2, Paxillin, CASL and p130CAS consistent with focal adhesion (FA) formation. We hypothesized that the collaborative signaling between β1 integrin and gp130 (IL-6 beta receptor, IL-6 signal transducer) was mediated by FA formation and proline-rich tyrosine kinase 2 (PYK2) activity. Both pharmacological and molecular targeting of PYK2 attenuated the amplification of STAT3 phosphorylation under co-stimulatory conditions. Co-culture of MM cells with patient bone marrow stromal cells (BMSC) showed similar β1 integrin-specific enhancement of PYK2 and STAT3 signaling. Molecular and pharmacological targeting of PYK2 specifically induced cell death and reduced clonogenic growth in BMSC-adherent myeloma cell lines, aldehyde dehydrogenase-positive MM cancer stem cells and patient specimens. Finally, PYK2 inhibition similarly attenuated MM progression in vivo. These data identify a novel PYK2-mediated survival pathway in MM cells and MM cancer stem cells within the context of microenvironmental cues, providing preclinical support for the use of the clinical stage FAK/PYK2 inhibitors for treatment of MM, especially in a minimal residual disease setting. PMID:26387544

Observability of Same-Charge Lepton Topologies in Fully Leptonic Top Quark Pair Events in CMS

NASA Astrophysics Data System (ADS)

Lowette, S.

2007-02-01

At the Large Hadron Collider dileptonic tbar t({+jets}) events can be selected with a relatively high signal-to-noise ratio and efficiency, with background events produced via Standard Model diagrams. Within the clean sample of these events, both isolated leptons have an opposite electric charge. In several models beyond the Standard Model tt/ bar t bar t(+{jets}) topologies are predicted, kinematically similar to the Standard Model tbar t({+jets}) signature, where both leptons have an equal electric charge. Such a signal of new physics can be diluted by the mis-identification of the leptons or their electric charge in Standard Model tbar t({+jets}) events. The observability of an excess of same-charge dilepton signals above the mis-reconstruction of the Standard Model background is presented, assuming the same topology. With an integrated luminosity of 30 fb-1, a same-charge dilepton signature of pp to tt/ bar t bar t events with a cross section larger than 1.2 pb is visible in the measurement of the ratio between same-charge and opposite-charge lepton pair events [J. D'Hondt, S. Lowette, G. Hammad, J. Heyninck, P. Van Mulders, ``Observability of same-charge lepton topology in dileptonic events t bar t'', CERN-CMS-NOTE-2006-065.

Shared performance monitor in a multiprocessor system

DOEpatents

Chiu, George; Gara, Alan G; Salapura, Valentina

2014-12-02

A performance monitoring unit (PMU) and method for monitoring performance of events occurring in a multiprocessor system. The multiprocessor system comprises a plurality of processor devices units, each processor device for generating signals representing occurrences of events in the processor device, and, a single shared counter resource for performance monitoring. The performance monitor unit is shared by all processor cores in the multiprocessor system. The PMU is further programmed to monitor event signals issued from non-processor devices.

Ephrin-B reverse signaling controls septation events at the embryonic midline through separate tyrosine phosphorylation-independent signaling avenues.

PubMed

Dravis, Christopher; Henkemeyer, Mark

2011-07-01

We report that the disruption of bidirectional signaling between ephrin-B2 and EphB receptors impairs morphogenetic cell-cell septation and closure events during development of the embryonic midline. A novel role for reverse signaling is identified in tracheoesophageal foregut septation, as animals lacking the cytoplasmic domain of ephrin-B2 present with laryngotracheoesophageal cleft (LTEC), while both EphB2/EphB3 forward signaling and ephrin-B2 reverse signaling are shown to be required for midline fusion of the palate. In a third midline event, EphB2/EphB3 are shown to mediate ventral abdominal wall closure by acting principally as ligands to stimulate ephrin-B reverse signaling. Analysis of new ephrin-B2(6YFΔV) and ephrin-B2(ΔV) mutants that specifically ablate ephrin-B2 tyrosine phosphorylation- and/or PDZ domain-mediated signaling indicates there are at least two distinct phosphorylation-independent components of reverse signaling. These involve both PDZ domain interactions and a non-canonical SH2/PDZ-independent form of reverse signaling that may utilize associations with claudin family tetraspan molecules, as EphB2 and activated ephrin-B2 molecules are specifically co-localized with claudins in epithelia at the point of septation. Finally, the developmental phenotypes described here mirror common human midline birth defects found with the VACTERL association, suggesting a molecular link to bidirectional signaling through B-subclass Ephs and ephrins. Copyright © 2011 Elsevier Inc. All rights reserved.

Developmental profile of localized spontaneous Ca2+ release events in the dendrites of rat hippocampal pyramidal neurons

PubMed Central

Miyazaki, Kenichi; Manita, Satoshi; Ross, William N.

2012-01-01

Summary Recent experiments demonstrate that localized spontaneous Ca2+ release events can be detected in the dendrites of pyramidal cells in the hippocampus and other neurons (J. Neurosci. 29:7833-7845, 2009). These events have some properties that resemble ryanodine receptor mediated “sparks” in myocytes, and some that resemble IP3 receptor mediated “puffs” in oocytes. They can be detected in the dendrites of rats of all tested ages between P3 and P80 (with sparser sampling in older rats), suggesting that they serve a general signaling function and are not just important in development. However, in younger rats the amplitudes of the events are larger than the amplitudes in older animals and almost as large as the amplitudes of Ca2+ signals from backpropagating action potentials (bAPs). The rise time of the event signal is fast at all ages and is comparable to the rise time of the bAP fluorescence signal at the same dendritic location. The decay time is slower in younger animals, primarily because of weaker Ca2+ extrusion mechanisms at that age. Diffusion away from a brief localized source is the major determinant of decay at all ages. A simple computational model closely simulates these events with extrusion rate the only age dependent variable. PMID:22951184

Identifying Driver Genomic Alterations in Cancers by Searching Minimum-Weight, Mutually Exclusive Sets

PubMed Central

Lu, Songjian; Lu, Kevin N.; Cheng, Shi-Yuan; Hu, Bo; Ma, Xiaojun; Nystrom, Nicholas; Lu, Xinghua

2015-01-01

An important goal of cancer genomic research is to identify the driving pathways underlying disease mechanisms and the heterogeneity of cancers. It is well known that somatic genome alterations (SGAs) affecting the genes that encode the proteins within a common signaling pathway exhibit mutual exclusivity, in which these SGAs usually do not co-occur in a tumor. With some success, this characteristic has been utilized as an objective function to guide the search for driver mutations within a pathway. However, mutual exclusivity alone is not sufficient to indicate that genes affected by such SGAs are in common pathways. Here, we propose a novel, signal-oriented framework for identifying driver SGAs. First, we identify the perturbed cellular signals by mining the gene expression data. Next, we search for a set of SGA events that carries strong information with respect to such perturbed signals while exhibiting mutual exclusivity. Finally, we design and implement an efficient exact algorithm to solve an NP-hard problem encountered in our approach. We apply this framework to the ovarian and glioblastoma tumor data available at the TCGA database, and perform systematic evaluations. Our results indicate that the signal-oriented approach enhances the ability to find informative sets of driver SGAs that likely constitute signaling pathways. PMID:26317392

JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

PubMed Central

Zeke, András; Misheva, Mariya

2016-01-01

SUMMARY The c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states. PMID:27466283

The serine/threonine-protein kinase/endoribonuclease IRE1α protects the heart against pressure overload-induced heart failure.

PubMed

Steiger, DeAnna; Yokota, Tomohiro; Li, Jin; Ren, Shuxun; Minamisawa, Susumu; Wang, Yibin

2018-05-16

Heart failure is associated with induction of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). The serine/threonine protein kinase/endoribonuclease IRE1α is a key protein in ER stress signal transduction. IRE1α activity can induce both protective UPR and apoptotic downstream signaling events, but the specific role for IRE1α activity in the heart is unknown. A major aim of this study was to characterize the specific contribution of IRE1α in cardiac physiology and pathogenesis. We used both cultured myocytes and a transgenic mouse line with inducible and cardiomyocyte-specific IRE1α overexpression as experimental models to achieve targeted IRE1α activation. IRE1α expression induced a potent but transient ER stress response in cardiomyocytes and did not cause significant effects in the intact heart under normal physiological condition. Furthermore, the IRE1α-activated transgenic heart responding to pressure overload exhibited preserved function and reduced fibrotic area, associated with increased adaptive UPR signaling and with blunted inflammatory and pathological gene expression. Therefore, we conclude that IRE1α induces transient ER stress signaling and confers a protective effect against pressure overload-induced pathological remodeling in the heart. To our knowledge, this report provides first direct evidence of a specific and protective role for IRE1α in the heart and reveals an interaction between ER stress signaling and inflammatory regulation in the pathologically stressed heart. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Assessment of the Absolute Excitatory Level of the Retina by Flicker ERG.

PubMed

Tanimoto, Naoyuki; Seeliger, Mathias W

2018-01-01

Electroretinography (ERG) is important for functional diagnostics of the retina. Types of information about retinal function obtainable by ERG differ depending on recording conditions, e.g., a combination of light stimulus and adaptation. In terms of stimulation, single-flash and flicker stimuli are frequently used because response properties have been well investigated, allowing an assessment of fundamental retinal functionality; for example, how photoreceptors and bipolar cells, including signal transmission between them, are affected under pathological conditions. Usually, ERGs are recorded with a nonzero lower cutoff frequency of amplifiers to avoid certain artifacts, and additionally, responses are averaged over time so that non-event-related signals are cancelled out. However, the improved signal quality is associated with a loss of information. Especially in steady-state flicker ERG, information about the absolute baseline of recordings is missing because the prestimulus baseline is not included on the recording trace as well as because a zero response is obtained in all cases in which the signal baseline stays constant for a sufficient amount of time. In other words, it is impossible to tell from the conventional flicker ERG whether a zero signal is obtained under conditions of maximal or no excitation of the visual system. In this chapter, we describe a direct current ERG protocol (featuring a lower cutoff frequency of zero) with repetitive single flashes mimicking conventional flicker that contains a defined onset. Using this recording protocol, it is possible to assess not only the absolute excitatory level of the retina but also the development of steady-state responses from the single flash response.

The Green Canyon Event as Recorded by the Atlantis OBS Node Survey

NASA Astrophysics Data System (ADS)

Dellinger, J. A.; Ehlers, J.; Clarke, R.

2006-12-01

On 10 February, 2006, a magnitude 5.2 earthquake occurred 260~km South of New Orleans, Louisiana, in the Green Canyon area of the United States Gulf of Mexico. Fortuitously, at the time of the earthquake an array of nearly 500 ocean-bottom-seismic nodes happened to be recording about 40~km SouthEast of the epicenter. These nodes were part of an ongoing oil-exploration 3D-seismic survey ("Atlantis patch 2"), and were designed to record oil-exploration air-gun seismic signals (with a dominant frequency of about 15~Hz), not low-frequency earthquake signals (1~Hz). The survey's own air guns, located about 7~km to the SouthEast of the array at the time of the event, were also repeatedly firing, generating large amounts of "noise" (at least for the purposes of analyzing the earthquake signal). Not surprisingly, when the data are plotted at their original sample rate they are dominated by the Atlantis survey's air-gun signal. When low passed with an upper cutoff of 2~Hz, however, the air-gun signals essentially vanish and underlying natural signals are clearly revealed. In land-seismic exploration dense 3D arrays of single geophones are used to characterize unwanted surface-wave energy. Beam forming the dense array allows the directions and phase velocities of wavefronts propagating across the array to be identified and localized so that receiver arrays can be designed that best attenuate the surface-wave noise. The 400-meter spacing of the Atlantis node array was designed to be optimally sparse for reflection-seismic processing. At 1~Hz, however, a 400-meter spacing becomes "dense" and we were able to use the same toolkit of programs originally developed for analyzing surface waves in land-seismic data to analyze the earthquake waves. The analysis reveals a complex and protracted series of arrivals spanning nearly 20~minutes of time. The expected sequence of earthquake arrivals from the North-NorthWest are followed by weaker sequences of arrivals of unknown origin from first the SouthEast and then from the East. It is hoped that these data can be used to help constrain the location, depth, and mechanism of the Green Canyon event. The authors wish to thank BP and BHPB for their permission to present this work, Fairfield for their enthusiasm in preserving the data, and CGG, WesternGeco, and Fugro for their cooperation in identifying other sources of man-made signals in the data.

A respiratory chain controlled signal transduction cascade in the mitochondrial intermembrane space mediates hydrogen peroxide signaling

PubMed Central

Patterson, Heide Christine; Gerbeth, Carolin; Thiru, Prathapan; Vögtle, Nora F.; Knoll, Marko; Shahsafaei, Aliakbar; Samocha, Kaitlin E.; Huang, Cher X.; Harden, Mark Michael; Song, Rui; Chen, Cynthia; Kao, Jennifer; Shi, Jiahai; Salmon, Wendy; Shaul, Yoav D.; Stokes, Matthew P.; Silva, Jeffrey C.; Bell, George W.; MacArthur, Daniel G.; Ruland, Jürgen; Meisinger, Chris; Lodish, Harvey F.

2015-01-01

Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) govern cellular homeostasis by inducing signaling. H2O2 modulates the activity of phosphatases and many other signaling molecules through oxidation of critical cysteine residues, which led to the notion that initiation of ROS signaling is broad and nonspecific, and thus fundamentally distinct from other signaling pathways. Here, we report that H2O2 signaling bears hallmarks of a regular signal transduction cascade. It is controlled by hierarchical signaling events resulting in a focused response as the results place the mitochondrial respiratory chain upstream of tyrosine-protein kinase Lyn, Lyn upstream of tyrosine-protein kinase SYK (Syk), and Syk upstream of numerous targets involved in signaling, transcription, translation, metabolism, and cell cycle regulation. The active mediators of H2O2 signaling colocalize as H2O2 induces mitochondria-associated Lyn and Syk phosphorylation, and a pool of Lyn and Syk reside in the mitochondrial intermembrane space. Finally, the same intermediaries control the signaling response in tissues and species responsive to H2O2 as the respiratory chain, Lyn, and Syk were similarly required for H2O2 signaling in mouse B cells, fibroblasts, and chicken DT40 B cells. Consistent with a broad role, the Syk pathway is coexpressed across tissues, is of early metazoan origin, and displays evidence of evolutionary constraint in the human. These results suggest that H2O2 signaling is under control of a signal transduction pathway that links the respiratory chain to the mitochondrial intermembrane space-localized, ubiquitous, and ancient Syk pathway in hematopoietic and nonhematopoietic cells. PMID:26438848

A respiratory chain controlled signal transduction cascade in the mitochondrial intermembrane space mediates hydrogen peroxide signaling.

PubMed

Patterson, Heide Christine; Gerbeth, Carolin; Thiru, Prathapan; Vögtle, Nora F; Knoll, Marko; Shahsafaei, Aliakbar; Samocha, Kaitlin E; Huang, Cher X; Harden, Mark Michael; Song, Rui; Chen, Cynthia; Kao, Jennifer; Shi, Jiahai; Salmon, Wendy; Shaul, Yoav D; Stokes, Matthew P; Silva, Jeffrey C; Bell, George W; MacArthur, Daniel G; Ruland, Jürgen; Meisinger, Chris; Lodish, Harvey F

2015-10-20

Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) govern cellular homeostasis by inducing signaling. H2O2 modulates the activity of phosphatases and many other signaling molecules through oxidation of critical cysteine residues, which led to the notion that initiation of ROS signaling is broad and nonspecific, and thus fundamentally distinct from other signaling pathways. Here, we report that H2O2 signaling bears hallmarks of a regular signal transduction cascade. It is controlled by hierarchical signaling events resulting in a focused response as the results place the mitochondrial respiratory chain upstream of tyrosine-protein kinase Lyn, Lyn upstream of tyrosine-protein kinase SYK (Syk), and Syk upstream of numerous targets involved in signaling, transcription, translation, metabolism, and cell cycle regulation. The active mediators of H2O2 signaling colocalize as H2O2 induces mitochondria-associated Lyn and Syk phosphorylation, and a pool of Lyn and Syk reside in the mitochondrial intermembrane space. Finally, the same intermediaries control the signaling response in tissues and species responsive to H2O2 as the respiratory chain, Lyn, and Syk were similarly required for H2O2 signaling in mouse B cells, fibroblasts, and chicken DT40 B cells. Consistent with a broad role, the Syk pathway is coexpressed across tissues, is of early metazoan origin, and displays evidence of evolutionary constraint in the human. These results suggest that H2O2 signaling is under control of a signal transduction pathway that links the respiratory chain to the mitochondrial intermembrane space-localized, ubiquitous, and ancient Syk pathway in hematopoietic and nonhematopoietic cells.

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

EPA Science Inventory

Effect of Arsenicals on the Expression of Cell Cycle Proteins and Early Signaling Events in Primary Human Keratinocytes.

Mudipalli, A, Owen R. D. and R. J. Preston, Environmental Carcinogenesis Division, USEPA, RTP, NC 27711.

Environmental exposure to arsenic is a m...

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.

Energy harvesting from localized dynamic transitions in post-buckled elastic beams under quasi-static loading

NASA Astrophysics Data System (ADS)

Borchani, Wassim

The deployability of structural health monitoring self-powered sensors relies on their capability to harvest energy from signals being monitored. Many of the signals required to assess the structure condition are quasi-static events which limits the levels of power that can be extracted. Several vibration-based techniques have been proposed to increase the transferred level of power and broaden the harvester operating bandwidth. However, these techniques require vibration input excitations at frequencies higher than dominant structural response frequencies which makes them inefficient and not suitable for ambient quasi-static excitations. This research proposes a novel sensing and energy harvesting technique at low frequencies using mechanical energy concentrators and triggers. These mechanisms consist of axially-loaded bilaterally-constrained beams with attached piezoelectric energy harvesters. When the quasi-static axial load reaches a certain mechanical threshold, a sudden snap-through mode-switching occurs. These transitions excite the attached piezoelectric scavengers with high-rate input accelerations, generating then electric power. The main objectives are to understand and model the post-buckling behavior of bilaterally-constrained beams, control it by tailoring geometry and material properties of the buckled elements or stacking them into system assemblies, and finally characterize the energy harvesting and sensing capability of the system under quasi-static excitations. The fundamental principle relies on the following concept. Under axial load, a straight slender beam buckles in the first buckling mode. The increased transverse deformations from a buckled shape lead to contact interaction with the lateral boundaries. The contact interaction generates transverse forces that induce the development of higher order buckling configurations. Transitions between the buckled configurations occur not only during loading, but also unloading. In this work, the post-buckling response of the bilaterally constrained beam subjected to axial loading is investigated experimentally, numerically, and theoretically. The capability of the system to generate electric energy under quasi-static excitation is also assessed experimentally. The post-buckling behavior is reproducible under cyclic loadings and independent of the input loading frequency. The static and dynamic response of the beam is theoretically studied using an energy method. The model adequately predicts the beam geometry at every loading stage, including the flattening behavior just before the snap buckling transitions, the mode transition events and the released kinetic energy as well as accelerations of the beam during transitions. The buckling transitions generate high kinetic energy and acceleration spikes. However, the location of the maximum acceleration differs from one transition to another. Tuning the parameters of the system affects dramatically the accelerations generated during snap-through transitions. However, it does not affect the number and spacing between these events. To achieve better control of the system, multiple slender beams with different geometric and material properties are stacked in parallel configurations. The system allows then to control the spacing between energy bursts and reduce the energy leakage in electronic circuits. As an application example, the mechanical energy concentrators and triggers were integrated with a piezo-floating gate events sensor. This allowed for harvesting and recording of bursts and impulses of released energy at very low frequencies. The system can be calibrated to determine the number of times the magnitude of the input signal exceeded a mechanical threshold. The mechanism allows for frequency up-conversion from the low input frequency (in the order of mHz) to the natural frequency of the piezoelectric scavenger.

A Fusion Model of Seismic and Hydro-Acoustic Propagation for Treaty Monitoring

NASA Astrophysics Data System (ADS)

Arora, Nimar; Prior, Mark

2014-05-01

We present an extension to NET-VISA (Network Processing Vertically Integrated Seismic Analysis), which is a probabilistic generative model of the propagation of seismic waves and their detection on a global scale, to incorporate hydro-acoustic data from the IMS (International Monitoring System) network. The new model includes the coupling of seismic waves into the ocean's SOFAR channel, as well as the propagation of hydro-acoustic waves from underwater explosions. The generative model is described in terms of multiple possible hypotheses -- seismic-to-hydro-acoustic, under-water explosion, other noise sources such as whales singing or icebergs breaking up -- that could lead to signal detections. We decompose each hypothesis into conditional probability distributions that are carefully analyzed and calibrated. These distributions include ones for detection probabilities, blockage in the SOFAR channel (including diffraction, refraction, and reflection around obstacles), energy attenuation, and other features of the resulting waveforms. We present a study of the various features that are extracted from the hydro-acoustic waveforms, and their correlations with each other as well the source of the energy. Additionally, an inference algorithm is presented that concurrently infers the seismic and under-water events, and associates all arrivals (aka triggers), both from seismic and hydro-acoustic stations, to the appropriate event, and labels the path taken by the wave. Finally, our results demonstrate that this fusion of seismic and hydro-acoustic data leads to very good performance. A majority of the under-water events that IDC (International Data Center) analysts built in 2010 are correctly located, and the arrivals that correspond to seismic-to-hydroacoustic coupling, the T phases, are mostly correctly identified. There is no loss in the accuracy of seismic events, in fact, there is a slight overall improvement.

Complex network inference from P300 signals: Decoding brain state under visual stimulus for able-bodied and disabled subjects

NASA Astrophysics Data System (ADS)

Gao, Zhong-Ke; Cai, Qing; Dong, Na; Zhang, Shan-Shan; Bo, Yun; Zhang, Jie

2016-10-01

Distinguishing brain cognitive behavior underlying disabled and able-bodied subjects constitutes a challenging problem of significant importance. Complex network has established itself as a powerful tool for exploring functional brain networks, which sheds light on the inner workings of the human brain. Most existing works in constructing brain network focus on phase-synchronization measures between regional neural activities. In contrast, we propose a novel approach for inferring functional networks from P300 event-related potentials by integrating time and frequency domain information extracted from each channel signal, which we show to be efficient in subsequent pattern recognition. In particular, we construct brain network by regarding each channel signal as a node and determining the edges in terms of correlation of the extracted feature vectors. A six-choice P300 paradigm with six different images is used in testing our new approach, involving one able-bodied subject and three disabled subjects suffering from multiple sclerosis, cerebral palsy, traumatic brain and spinal-cord injury, respectively. We then exploit global efficiency, local efficiency and small-world indices from the derived brain networks to assess the network topological structure associated with different target images. The findings suggest that our method allows identifying brain cognitive behaviors related to visual stimulus between able-bodied and disabled subjects.

The effects of methylphenidate on cerebral responses to conflict anticipation and unsigned prediction error in a stop-signal task.

PubMed

Manza, Peter; Hu, Sien; Ide, Jaime S; Farr, Olivia M; Zhang, Sheng; Leung, Hoi-Chung; Li, Chiang-shan R

2016-03-01

To adapt flexibly to a rapidly changing environment, humans must anticipate conflict and respond to surprising, unexpected events. To this end, the brain estimates upcoming conflict on the basis of prior experience and computes unsigned prediction error (UPE). Although much work implicates catecholamines in cognitive control, little is known about how pharmacological manipulation of catecholamines affects the neural processes underlying conflict anticipation and UPE computation. We addressed this issue by imaging 24 healthy young adults who received a 45 mg oral dose of methylphenidate (MPH) and 62 matched controls who did not receive MPH prior to performing the stop-signal task. We used a Bayesian Dynamic Belief Model to make trial-by-trial estimates of conflict and UPE during task performance. Replicating previous research, the control group showed anticipation-related activation in the presupplementary motor area and deactivation in the ventromedial prefrontal cortex and parahippocampal gyrus, as well as UPE-related activations in the dorsal anterior cingulate, insula, and inferior parietal lobule. In group comparison, MPH increased anticipation activity in the bilateral caudate head and decreased UPE activity in each of the aforementioned regions. These findings highlight distinct effects of catecholamines on the neural mechanisms underlying conflict anticipation and UPE, signals critical to learning and adaptive behavior. © The Author(s) 2016.

The effects of methylphenidate on cerebral responses to conflict anticipation and unsigned prediction error in a stop-signal task

PubMed Central

Manza, Peter; Hu, Sien; Ide, Jaime S; Farr, Olivia M; Zhang, Sheng; Leung, Hoi-Chung; Li, Chiang-shan R

2016-01-01

To adapt flexibly to a rapidly changing environment, humans must anticipate conflict and respond to surprising, unexpected events. To this end, the brain estimates upcoming conflict on the basis of prior experience and computes unsigned prediction error (UPE). Although much work implicates catecholamines in cognitive control, little is known about how pharmacological manipulation of catecholamines affects the neural processes underlying conflict anticipation and UPE computation. We addressed this issue by imaging 24 healthy young adults who received a 45 mg oral dose of methylphenidate (MPH) and 62 matched controls who did not receive MPH prior to performing the stop-signal task. We used a Bayesian Dynamic Belief Model to make trial-by-trial estimates of conflict and UPE during task performance. Replicating previous research, the control group showed anticipation-related activation in the presupplementary motor area and deactivation in the ventromedial prefrontal cortex and parahippocampal gyrus, as well as UPE-related activations in the dorsal anterior cingulate, insula, and inferior parietal lobule. In group comparison, MPH increased anticipation activity in the bilateral caudate head and decreased UPE activity in each of the aforementioned regions. These findings highlight distinct effects of catecholamines on the neural mechanisms underlying conflict anticipation and UPE, signals critical to learning and adaptive behavior. PMID:26755547

Intrapartum electrocardiogram alteration in fetuses with congenital heart disease: a case-control study.

PubMed

Gay, Estelle; Bornallet, Géraldine; Gaucherand, Pascal; Doret, Muriel

2015-11-01

To assess if the fetal electrocardiogram especially ST segment is modified by congenital heart diseases: modifications in frequencies of the different ST events and modifications in signal quality. A retrospective case-control study, comparing frequencies of the different ST events and the quality of the signal between fetuses with congenital heart diseases and fetuses without congenital heart disease. From 2000 to 2011, fifty-eight fetuses with congenital heart disease had their heart rate recording using a STAN device during labor. Control group was fetuses who were born just before a case and had a STAN as a second line for intrapartum surveillance. Cases and controls were matched on parity, gestational age at birth, presence of growth restriction and umbilical artery pH. Frequencies of the different ST event and quality of the signal were first analyzed for the global labor recording, and then separately for the first and the second phase of labor. No statistically significant difference in ST event frequencies between fetuses with congenital heart disease and the control group was found. Regarding the quality of the signal, 11.49% (±18.82) of recording time is a signal loss for fetus with congenital heart disease whereas only 5.18% (±10.67) for the control group (p=0.028). This is the first study investigating for intrapartum electrocardiogram modification in fetus with congenital heart disease. Congenital heart diseases do not modify frequencies of ST events. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2016-09-01

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

Topological properties of flat electroencephalography's state space

NASA Astrophysics Data System (ADS)

Ken, Tan Lit; Ahmad, Tahir bin; Mohd, Mohd Sham bin; Ngien, Su Kong; Suwa, Tohru; Meng, Ong Sie

2016-02-01

Neuroinverse problem are often associated with complex neuronal activity. It involves locating problematic cell which is highly challenging. While epileptic foci localization is possible with the aid of EEG signals, it relies greatly on the ability to extract hidden information or pattern within EEG signals. Flat EEG being an enhancement of EEG is a way of viewing electroencephalograph on the real plane. In the perspective of dynamical systems, Flat EEG is equivalent to epileptic seizure hence, making it a great platform to study epileptic seizure. Throughout the years, various mathematical tools have been applied on Flat EEG to extract hidden information that is hardly noticeable by traditional visual inspection. While these tools have given worthy results, the journey towards understanding seizure process completely is yet to be succeeded. Since the underlying structure of Flat EEG is dynamic and is deemed to contain wealthy information regarding brainstorm, it would certainly be appealing to explore in depth its structures. To better understand the complex seizure process, this paper studies the event of epileptic seizure via Flat EEG in a more general framework by means of topology, particularly, on the state space where the event of Flat EEG lies.

pyAudioAnalysis: An Open-Source Python Library for Audio Signal Analysis.

PubMed

Giannakopoulos, Theodoros

2015-01-01

Audio information plays a rather important role in the increasing digital content that is available today, resulting in a need for methodologies that automatically analyze such content: audio event recognition for home automations and surveillance systems, speech recognition, music information retrieval, multimodal analysis (e.g. audio-visual analysis of online videos for content-based recommendation), etc. This paper presents pyAudioAnalysis, an open-source Python library that provides a wide range of audio analysis procedures including: feature extraction, classification of audio signals, supervised and unsupervised segmentation and content visualization. pyAudioAnalysis is licensed under the Apache License and is available at GitHub (https://github.com/tyiannak/pyAudioAnalysis/). Here we present the theoretical background behind the wide range of the implemented methodologies, along with evaluation metrics for some of the methods. pyAudioAnalysis has been already used in several audio analysis research applications: smart-home functionalities through audio event detection, speech emotion recognition, depression classification based on audio-visual features, music segmentation, multimodal content-based movie recommendation and health applications (e.g. monitoring eating habits). The feedback provided from all these particular audio applications has led to practical enhancement of the library.

Multiple Component Event-Related Potential (mcERP) Estimation

NASA Technical Reports Server (NTRS)

Knuth, K. H.; Clanton, S. T.; Shah, A. S.; Truccolo, W. A.; Ding, M.; Bressler, S. L.; Trejo, L. J.; Schroeder, C. E.; Clancy, Daniel (Technical Monitor)

2002-01-01

We show how model-based estimation of the neural sources responsible for transient neuroelectric signals can be improved by the analysis of single trial data. Previously, we showed that a multiple component event-related potential (mcERP) algorithm can extract the responses of individual sources from recordings of a mixture of multiple, possibly interacting, neural ensembles. McERP also estimated single-trial amplitudes and onset latencies, thus allowing more accurate estimation of ongoing neural activity during an experimental trial. The mcERP algorithm is related to informax independent component analysis (ICA); however, the underlying signal model is more physiologically realistic in that a component is modeled as a stereotypic waveshape varying both in amplitude and onset latency from trial to trial. The result is a model that reflects quantities of interest to the neuroscientist. Here we demonstrate that the mcERP algorithm provides more accurate results than more traditional methods such as factor analysis and the more recent ICA. Whereas factor analysis assumes the sources are orthogonal and ICA assumes the sources are statistically independent, the mcERP algorithm makes no such assumptions thus allowing investigators to examine interactions among components by estimating the properties of single-trial responses.

Nuclear factor-kappaB activation and postischemic inflammation are suppressed in CD36-null mice after middle cerebral artery occlusion.

PubMed

Kunz, Alexander; Abe, Takato; Hochrainer, Karin; Shimamura, Munehisa; Anrather, Josef; Racchumi, Gianfranco; Zhou, Ping; Iadecola, Costantino

2008-02-13

CD36, a class-B scavenger receptor involved in multiple functions, including inflammatory signaling, may also contribute to ischemic brain injury through yet unidentified mechanisms. We investigated whether CD36 participates in the molecular events underlying the inflammatory reaction that accompanies cerebral ischemia and may contribute to the tissue damage. We found that activation of nuclear factor-kappaB, a transcription factor that coordinates postischemic gene expression, is attenuated in CD36-null mice subjected to middle cerebral artery occlusion. The infiltration of neutrophils and the glial reaction induced by cerebral ischemia were suppressed. Treatment with an inhibitor of inducible nitric oxide synthase, an enzyme that contributes to the tissue damage, reduced ischemic brain injury in wild-type mice, but not in CD36 nulls. In contrast to cerebral ischemia, the molecular and cellular inflammatory changes induced by intracerebroventricular injection of interleukin-1beta were not attenuated in CD36-null mice. The findings unveil a novel role of CD36 in early molecular events leading to nuclear factor-kappaB activation and postischemic inflammation. Inhibition of CD36 signaling may be a valuable therapeutic approach to counteract the deleterious effects of postischemic inflammation.

pyAudioAnalysis: An Open-Source Python Library for Audio Signal Analysis

PubMed Central

Giannakopoulos, Theodoros

2015-01-01

Audio information plays a rather important role in the increasing digital content that is available today, resulting in a need for methodologies that automatically analyze such content: audio event recognition for home automations and surveillance systems, speech recognition, music information retrieval, multimodal analysis (e.g. audio-visual analysis of online videos for content-based recommendation), etc. This paper presents pyAudioAnalysis, an open-source Python library that provides a wide range of audio analysis procedures including: feature extraction, classification of audio signals, supervised and unsupervised segmentation and content visualization. pyAudioAnalysis is licensed under the Apache License and is available at GitHub (https://github.com/tyiannak/pyAudioAnalysis/). Here we present the theoretical background behind the wide range of the implemented methodologies, along with evaluation metrics for some of the methods. pyAudioAnalysis has been already used in several audio analysis research applications: smart-home functionalities through audio event detection, speech emotion recognition, depression classification based on audio-visual features, music segmentation, multimodal content-based movie recommendation and health applications (e.g. monitoring eating habits). The feedback provided from all these particular audio applications has led to practical enhancement of the library. PMID:26656189

Can machine learning complement traditional medical device surveillance? A case study of dual-chamber implantable cardioverter–defibrillators

PubMed Central

Ross, Joseph S; Bates, Jonathan; Parzynski, Craig S; Akar, Joseph G; Curtis, Jeptha P; Desai, Nihar R; Freeman, James V; Gamble, Ginger M; Kuntz, Richard; Li, Shu-Xia; Marinac-Dabic, Danica; Masoudi, Frederick A; Normand, Sharon-Lise T; Ranasinghe, Isuru; Shaw, Richard E; Krumholz, Harlan M

2017-01-01

Background Machine learning methods may complement traditional analytic methods for medical device surveillance. Methods and results Using data from the National Cardiovascular Data Registry for implantable cardioverter–defibrillators (ICDs) linked to Medicare administrative claims for longitudinal follow-up, we applied three statistical approaches to safety-signal detection for commonly used dual-chamber ICDs that used two propensity score (PS) models: one specified by subject-matter experts (PS-SME), and the other one by machine learning-based selection (PS-ML). The first approach used PS-SME and cumulative incidence (time-to-event), the second approach used PS-SME and cumulative risk (Data Extraction and Longitudinal Trend Analysis [DELTA]), and the third approach used PS-ML and cumulative risk (embedded feature selection). Safety-signal surveillance was conducted for eleven dual-chamber ICD models implanted at least 2,000 times over 3 years. Between 2006 and 2010, there were 71,948 Medicare fee-for-service beneficiaries who received dual-chamber ICDs. Cumulative device-specific unadjusted 3-year event rates varied for three surveyed safety signals: death from any cause, 12.8%–20.9%; nonfatal ICD-related adverse events, 19.3%–26.3%; and death from any cause or nonfatal ICD-related adverse event, 27.1%–37.6%. Agreement among safety signals detected/not detected between the time-to-event and DELTA approaches was 90.9% (360 of 396, k=0.068), between the time-to-event and embedded feature-selection approaches was 91.7% (363 of 396, k=−0.028), and between the DELTA and embedded feature selection approaches was 88.1% (349 of 396, k=−0.042). Conclusion Three statistical approaches, including one machine learning method, identified important safety signals, but without exact agreement. Ensemble methods may be needed to detect all safety signals for further evaluation during medical device surveillance. PMID:28860874

On the time lags of the LIGO signals

NASA Astrophysics Data System (ADS)

Creswell, James; von Hausegger, Sebastian; Jackson, Andrew D.; Liu, Hao; Naselsky, Pavel

2017-08-01

To date, the LIGO collaboration has detected three gravitational wave (GW) events appearing in both its Hanford and Livingston detectors. In this article we reexamine the LIGO data with regard to correlations between the two detectors. With special focus on GW150914, we report correlations in the detector noise which, at the time of the event, happen to be maximized for the same time lag as that found for the event itself. Specifically, we analyze correlations in the calibration lines in the vicinity of 35 Hz as well as the residual noise in the data after subtraction of the best-fit theoretical templates. The residual noise for the other two events, GW151226 and GW170104, exhibits similar behavior. A clear distinction between signal and noise therefore remains to be established in order to determine the contribution of gravitational waves to the detected signals.

Distinguishing high surf from volcanic long-period earthquakes

USGS Publications Warehouse

Lyons, John; Haney, Matt; Fee, David; Paskievitch, John F.

2014-01-01

Repeating long-period (LP) earthquakes are observed at active volcanoes worldwide and are typically attributed to unsteady pressure fluctuations associated with fluid migration through the volcanic plumbing system. Nonvolcanic sources of LP signals include ice movement and glacial outburst floods, and the waveform characteristics and frequency content of these events often make them difficult to distinguish from volcanic LP events. We analyze seismic and infrasound data from an LP swarm recorded at Pagan volcano on 12–14 October 2013 and compare the results to ocean wave data from a nearby buoy. We demonstrate that although the events show strong similarity to volcanic LP signals, the events are not volcanic but due to intense surf generated by a passing typhoon. Seismo-acoustic methods allow for rapid distinction of volcanic LP signals from those generated by large surf and other sources, a critical task for volcano monitoring.

On the time lags of the LIGO signals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Creswell, James; Von Hausegger, Sebastian; Liu, Hao

To date, the LIGO collaboration has detected three gravitational wave (GW) events appearing in both its Hanford and Livingston detectors. In this article we reexamine the LIGO data with regard to correlations between the two detectors. With special focus on GW150914, we report correlations in the detector noise which, at the time of the event, happen to be maximized for the same time lag as that found for the event itself. Specifically, we analyze correlations in the calibration lines in the vicinity of 35 Hz as well as the residual noise in the data after subtraction of the best-fit theoreticalmore » templates. The residual noise for the other two events, GW151226 and GW170104, exhibits similar behavior. A clear distinction between signal and noise therefore remains to be established in order to determine the contribution of gravitational waves to the detected signals.« less

The application of a piezo-resistive cardiorespiratory sensor system in an automobile safety belt.

PubMed

Hamdani, Syed Talha Ali; Fernando, Anura

2015-03-30

Respiratory and heart failure are conditions that can occur with little warning and may also be difficult to predict. Therefore continuous monitoring of these bio-signals is advantageous for ensuring human health. The car safety belt is mainly designed to secure the occupants of the vehicle in the event of an accident. In the current research a prototype safety belt is developed, which is used to acquire respiratory and heart signals, under laboratory conditions. The current safety belt is constructed using a copper ink based nonwoven material, which works based on the piezo-resistive effect due to the pressure exerted on the sensor as a result of expansion of the thorax/abdomen area of the body for respiration and due to the principle of ballistocardiography (BCG) in heart signal sensing. In this research, the development of a theoretical model to qualitatively describe the piezo-resistive material is also presented in order to predict the relative change in the resistance of the piezo-resistive material due to the pressure applied.

SMAD7 directly converts human embryonic stem cells to telencephalic fate by a default mechanism

PubMed Central

Ozair, Mohammad Zeeshan; Noggle, Scott; Warmflash, Aryeh; Krzyspiak, Joanna Ela; Brivanlou, Ali H.

2013-01-01

Human embryonic stem cells (hESCs) provide a valuable window into the dissection of the molecular circuitry underlying the early formation of the human forebrain. However, dissection of signaling events in forebrain development using current protocols is complicated by non-neural contamination and fluctuation of extrinsic influences. Here we show that SMAD7, a cell-intrinsic inhibitor of TGFβ signaling, is sufficient to directly convert pluripotent hESCs to an anterior neural fate. Time-course gene expression revealed down-regulation of MAPK components, and combining MEK1/2 inhibition with SMAD7-mediated TGFβ inhibition promoted telencephalic conversion. FGF-MEK and TGFβ-SMAD signaling maintain hESCs by promoting pluripotency genes and repressing neural genes. Our findings suggest that in the absence of these cues, pluripotent cells simply revert to a program of neural conversion. Hence the “primed” state of hESCs requires inhibition of the “default” state of neural fate acquisition. This has parallels in amphibians, suggesting an evolutionarily conserved mechanism. PMID:23034881

The role of redox mechanisms in hepatic chronic wound healing and fibrogenesis

PubMed Central

2012-01-01

Under physiological conditions, intracellular and tissue levels of reactive oxygen species (ROS) are carefully controlled and employed as fine modulators of signal transduction, gene expression and cell functional responses (redox signaling). A significant derangement in redox homeostasis, resulting in sustained levels of oxidative stress and related mediators, plays a role in the pathogenesis of human diseases characterized by chronic inflammation, chronic activation of wound healing and tissue fibrogenesis, including chronic liver diseases. In this chapter major concepts and mechanisms in redox signaling will be briefly recalled to introduce a number of selected examples of redox-related mechanisms that can actively contribute to critical events in the natural history of a chronic liver diseases, including induction of cell death, perpetuation of chronic inflammatory responses and fibrogenesis. A major focus will be on redox-dependent mechanisms involved in the modulation of phenotypic responses of activated, myofibroblast-like, hepatic stellate cells (HSC/MFs), still considered as the most relevant pro-fibrogenic cells operating in chronic liver diseases. PMID:23259696

Vascular-mediated signalling involved in early phosphate stress response in plants.

PubMed

Zhang, Zhaoliang; Zheng, Yi; Ham, Byung-Kook; Chen, Jieyu; Yoshida, Akiko; Kochian, Leon V; Fei, Zhangjun; Lucas, William J

2016-04-04

Depletion of finite global rock phosphate (Pi) reserves will impose major limitations on future agricultural productivity and food security. Hence, modern breeding programmes seek to develop Pi-efficient crops with sustainable yields under reduced Pi fertilizer inputs. In this regard, although the long-term responses of plants to Pi stress are well documented, the early signalling events have yet to be elucidated. Here, we show plant tissue-specific responses to early Pi stress at the transcription level and a predominant role of the plant vascular system in this process. Specifically, imposition of Pi stress induces rapid and major changes in the mRNA population in the phloem translocation stream, and grafting studies have revealed that many hundreds of phloem-mobile mRNAs are delivered to specific sink tissues. We propose that the shoot vascular system acts as the site of root-derived Pi stress perception, and the phloem serves to deliver a cascade of signals to various sinks, presumably to coordinate whole-plant Pi homeostasis.

Effects of multiple scattering on time- and depth-resolved signals in airborne lidar systems

NASA Technical Reports Server (NTRS)

Punjabi, A.; Venable, D. D.

1986-01-01

A semianalytic Monte Carlo radiative transfer model (SALMON) is employed to probe the effects of multiple-scattering events on the time- and depth-resolved lidar signals from homogeneous aqueous media. The effective total attenuation coefficients in the single-scattering approximation are determined as functions of dimensionless parameters characterizing the lidar system and the medium. Results show that single-scattering events dominate when these parameters are close to their lower bounds and that when their values exceed unity multiple-scattering events dominate.

Microseismic Monitoring of the Olivine → Spinel Transition in Fayalite Under Non-Hydrostatic Stress

NASA Astrophysics Data System (ADS)

Officer, T.; Secco, R. A.

2016-12-01

In subduction zones, deep earthquakes are thought to be associated with faulting that arises from phase transformations. In order to test the viability of this mechanism experimentally, it is necessary to make microseismic measurements while the mineral under investigation is subjected to the pressure and temperature (P,T) environment at depth. A system has been developed capable of making in situ acoustic emission (AE) measurements on samples under P,T conditions representative of the upper mantle and transition zone. Experiments are performed in a 3000-ton multi-anvil press using an 18/11 octahedral cell with 6 piezoelectric transducers mounted on the rear side of the anvils. AE signals are collected at a sampling rate of 40 MHz using a triggered system and a data buffer for continuous recording so full waveforms of AE events are captured. The use of multiple transducers distributed in a microseismic array allows for events to be located within the sample through automatic arrival time picking and least squares inversion techniques. The multi-anvil apparatus constitutes an inherently noisy environment both acoustically and electrically, therefore methods of noise reduction were developed and will be discussed. This technique has been used to measure acoustic signals generated from the fracturing of quartz beads during high pressure deformation and to investigate the possibility that the phase transformation from olivine to spinel, known to occur in subduction zones, is associated with deep-focus earthquakes (300 - 690 km depth). The analog material fayalite (Fe2SiO4), the iron end member of olivine, has been examined. Information about its synthesis and sintering will be discussed as well as results of AE experiments on samples experiencing deviatoric stress under high pressure (P = 4-9 GPa) and high temperature (T = 773-1273 K) conditions in the spinel stability field.

Bioelectric memory: modeling resting potential bistability in amphibian embryos and mammalian cells.

PubMed

Law, Robert; Levin, Michael

2015-10-15

Bioelectric gradients among all cells, not just within excitable nerve and muscle, play instructive roles in developmental and regenerative pattern formation. Plasma membrane resting potential gradients regulate cell behaviors by regulating downstream transcriptional and epigenetic events. Unlike neurons, which fire rapidly and typically return to the same polarized state, developmental bioelectric signaling involves many cell types stably maintaining various levels of resting potential during morphogenetic events. It is important to begin to quantitatively model the stability of bioelectric states in cells, to understand computation and pattern maintenance during regeneration and remodeling. To facilitate the analysis of endogenous bioelectric signaling and the exploitation of voltage-based cellular controls in synthetic bioengineering applications, we sought to understand the conditions under which somatic cells can stably maintain distinct resting potential values (a type of state memory). Using the Channelpedia ion channel database, we generated an array of amphibian oocyte and mammalian membrane models for voltage evolution. These models were analyzed and searched, by simulation, for a simple dynamical property, multistability, which forms a type of voltage memory. We find that typical mammalian models and amphibian oocyte models exhibit bistability when expressing different ion channel subsets, with either persistent sodium or inward-rectifying potassium, respectively, playing a facilitative role in bistable memory formation. We illustrate this difference using fast sodium channel dynamics for which a comprehensive theory exists, where the same model exhibits bistability under mammalian conditions but not amphibian conditions. In amphibians, potassium channels from the Kv1.x and Kv2.x families tend to disrupt this bistable memory formation. We also identify some common principles under which physiological memory emerges, which suggest specific strategies for implementing memories in bioengineering contexts. Our results reveal conditions under which cells can stably maintain one of several resting voltage potential values. These models suggest testable predictions for experiments in developmental bioelectricity, and illustrate how cells can be used as versatile physiological memory elements in synthetic biology, and unconventional computation contexts.

A new solution of measuring thermal response of prestressed concrete bridge girders for structural health monitoring

NASA Astrophysics Data System (ADS)

Jiao, Pengcheng; Borchani, Wassim; Hasni, Hassene; Lajnef, Nizar

2017-08-01

This study develops a novel buckling-based mechanism to measure the thermal response of prestressed concrete bridge girders under continuous temperature changes for structural health monitoring. The measuring device consists of a bilaterally constrained beam and a piezoelectric polyvinylidene fluoride transducer that is attached to the beam. Under thermally induced displacement, the slender beam is buckled. The post-buckling events are deployed to convert the low-rate and low-frequency excitations into localized high-rate motions and, therefore, the attached piezoelectric transducer is triggered to generate electrical signals. Attaching the measuring device to concrete bridge girders, the electrical signals are used to detect the thermal response of concrete bridges. Finite element simulations are conducted to obtain the displacement of prestressed concrete girders under thermal loads. Using the thermal-induced displacement as input, experiments are carried out on a 3D printed measuring device to investigate the buckling response and corresponding electrical signals. A theoretical model is developed based on the nonlinear Euler-Bernoulli beam theory and large deformation assumptions to predict the buckling mode transitions of the beam. Based on the presented theoretical model, the geometry properties of the measuring device can be designed such that its buckling response is effectively controlled. Consequently, the thermally induced displacement can be designed as limit states to detect excessive thermal loads on concrete bridge girders. The proposed solution sufficiently measures the thermal response of concrete bridges.

Initial tsunami signals in the lithosphere-ocean-atmosphere medium

NASA Astrophysics Data System (ADS)

Novik, O.; Ershov, S.; Mikhaylovskaya, I.

Satellite and ground based instrumentations for monitoring of dynamical processes under the Ocean floor 3 4 of the Earth surface and resulting catastrophic events should be adapted to unknown physical nature of transformation of the oceanic lithosphere s energy of seismogenic deformations into measurable acoustic electromagnetic EM temperature and hydrodynamic tsunami waves To describe the initial up to a tsunami wave far from a shore stage of this transformation and to understand mechanism of EM signals arising above the Ocean during seismic activation we formulate a nonlinear mathematical model of seismo-hydro-EM geophysical field interaction in the lithosphere-Ocean-atmosphere medium from the upper mantle under the Ocean up to the ionosphere domain D The model is based on the theory of elasticity electrodynamics fluid dynamics thermodynamics and geophysical data On the basis of this model and its mathematical investigation we calculate generation and propagation of different see above waves in the basin of a model marginal sea the data on the central part of the Sea of Japan were used At the moment t 0 the dynamic interaction process is supposed to be caused by weak may be precursory sub-vertical elastic displacements with the amplitude duration and main frequency of the order of a few cm sec and tenth of Hz respectively at the depth of 37 km under the sea level i e in the upper mantle Other seismic excitations may be considered as well The lithosphere EM signal is generated in the upper mantle conductive

First all-flavor neutrino pointlike source search with the ANTARES neutrino telescope

NASA Astrophysics Data System (ADS)

Albert, A.; André, M.; Anghinolfi, M.; Anton, G.; Ardid, M.; Aubert, J.-J.; Avgitas, T.; Baret, B.; Barrios-Martí, J.; Basa, S.; Belhorma, B.; Bertin, V.; Biagi, S.; Bormuth, R.; Bourret, S.; Bouwhuis, M. C.; Brânzaş, H.; Bruijn, R.; Brunner, J.; Busto, J.; Capone, A.; Caramete, L.; Carr, J.; Celli, S.; Cherkaoui El Moursli, R.; Chiarusi, T.; Circella, M.; Coelho, J. A. B.; Coleiro, A.; Coniglione, R.; Costantini, H.; Coyle, P.; Creusot, A.; Díaz, A. F.; Deschamps, A.; de Bonis, G.; Distefano, C.; di Palma, I.; Domi, A.; Donzaud, C.; Dornic, D.; Drouhin, D.; Eberl, T.; El Bojaddaini, I.; El Khayati, N.; Elsässer, D.; Enzenhöfer, A.; Ettahiri, A.; Fassi, F.; Felis, I.; Fusco, L. A.; Galatà, S.; Gay, P.; Giordano, V.; Glotin, H.; Grégoire, T.; Gracia Ruiz, R.; Graf, K.; Hallmann, S.; van Haren, H.; Heijboer, A. J.; Hello, Y.; Hernández-Rey, J. J.; Hößl, J.; Hofestädt, J.; Hugon, C.; Illuminati, G.; James, C. W.; de Jong, M.; Jongen, M.; Kadler, M.; Kalekin, O.; Katz, U.; Kießling, D.; Kouchner, A.; Kreter, M.; Kreykenbohm, I.; Kulikovskiy, V.; Lachaud, C.; Lahmann, R.; Lefèvre, D.; Leonora, E.; Lotze, M.; Loucatos, S.; Marcelin, M.; Margiotta, A.; Marinelli, A.; Martínez-Mora, J. A.; Mele, R.; Melis, K.; Michael, T.; Migliozzi, P.; Moussa, A.; Navas, S.; Nezri, E.; Organokov, M.; Pǎvǎlaş, G. E.; Pellegrino, C.; Perrina, C.; Piattelli, P.; Popa, V.; Pradier, T.; Quinn, L.; Racca, C.; Riccobene, G.; Sánchez-Losa, A.; Saldaña, M.; Salvadori, I.; Samtleben, D. F. E.; Sanguineti, M.; Sapienza, P.; Schüssler, F.; Sieger, C.; Spurio, M.; Stolarczyk, Th.; Taiuti, M.; Tayalati, Y.; Trovato, A.; Turpin, D.; Tönnis, C.; Vallage, B.; van Elewyck, V.; Versari, F.; Vivolo, D.; Vizzoca, A.; Wilms, J.; Zornoza, J. D.; Zúñiga, J.; ANTARES Collaboration

2017-10-01

A search for cosmic neutrino sources using the data collected with the ANTARES neutrino telescope between early 2007 and the end of 2015 is performed. For the first time, all neutrino interactions—charged- and neutral-current interactions of all flavors—are considered in a search for point-like sources with the ANTARES detector. In previous analyses, only muon neutrino charged-current interactions were used. This is achieved by using a novel reconstruction algorithm for shower-like events in addition to the standard muon track reconstruction. The shower channel contributes about 23% of all signal events for an E-2 energy spectrum. No significant excess over background is found. The most signal-like cluster of events is located at (α ,δ )=(343.8 ° ,23.5 ° ) with a significance of 1.9 σ . The neutrino flux sensitivity of the search is about E2d Φ /d E =6 ×10-9 GeV cm-2 s-1 for declinations from -90 ° up to -42 ° , and below 10-8 GeV cm-2 s-1 for declinations up to 5°. The directions of 106 source candidates and 13 muon track events from the IceCube high-energy sample events are investigated for a possible neutrino signal and upper limits on the signal flux are determined.

Discrimination of Dynamic Tactile Contact by Temporally Precise Event Sensing in Spiking Neuromorphic Networks

PubMed Central

Lee, Wang Wei; Kukreja, Sunil L.; Thakor, Nitish V.

2017-01-01

This paper presents a neuromorphic tactile encoding methodology that utilizes a temporally precise event-based representation of sensory signals. We introduce a novel concept where touch signals are characterized as patterns of millisecond precise binary events to denote pressure changes. This approach is amenable to a sparse signal representation and enables the extraction of relevant features from thousands of sensing elements with sub-millisecond temporal precision. We also proposed measures adopted from computational neuroscience to study the information content within the spiking representations of artificial tactile signals. Implemented on a state-of-the-art 4096 element tactile sensor array with 5.2 kHz sampling frequency, we demonstrate the classification of transient impact events while utilizing 20 times less communication bandwidth compared to frame based representations. Spiking sensor responses to a large library of contact conditions were also synthesized using finite element simulations, illustrating an 8-fold improvement in information content and a 4-fold reduction in classification latency when millisecond-precise temporal structures are available. Our research represents a significant advance, demonstrating that a neuromorphic spatiotemporal representation of touch is well suited to rapid identification of critical contact events, making it suitable for dynamic tactile sensing in robotic and prosthetic applications. PMID:28197065

Alternative source models of very low frequency events

NASA Astrophysics Data System (ADS)

Gomberg, J.; Agnew, D. C.; Schwartz, S. Y.

2016-09-01

We present alternative source models for very low frequency (VLF) events, previously inferred to be radiation from individual slow earthquakes that partly fill the period range between slow slip events lasting thousands of seconds and low-frequency earthquakes (LFE) with durations of tenths of a second. We show that VLF events may emerge from bandpass filtering a sum of clustered, shorter duration, LFE signals, believed to be the components of tectonic tremor. Most published studies show VLF events occurring concurrently with tremor bursts and LFE signals. Our analysis of continuous data from Costa Rica detected VLF events only when tremor was also occurring, which was only 7% of the total time examined. Using analytic and synthetic models, we show that a cluster of LFE signals produces the distinguishing characteristics of VLF events, which may be determined by the cluster envelope. The envelope may be diagnostic of a single, dynamic, slowly slipping event that propagates coherently over kilometers or represents a narrowly band-passed version of nearly simultaneous arrivals of radiation from slip on multiple higher stress drop and/or faster propagating slip patches with dimensions of tens of meters (i.e., LFE sources). Temporally clustered LFE sources may be triggered by single or multiple distinct aseismic slip events or represent the nearly simultaneous chance occurrence of background LFEs. Given the nonuniqueness in possible source durations, we suggest it is premature to draw conclusions about VLF event sources or how they scale.

Alternative source models of very low frequency events

USGS Publications Warehouse

Gomberg, Joan S.; Agnew, D.C.; Schwartz, S.Y.

2016-01-01

We present alternative source models for very low frequency (VLF) events, previously inferred to be radiation from individual slow earthquakes that partly fill the period range between slow slip events lasting thousands of seconds and low-frequency earthquakes (LFE) with durations of tenths of a second. We show that VLF events may emerge from bandpass filtering a sum of clustered, shorter duration, LFE signals, believed to be the components of tectonic tremor. Most published studies show VLF events occurring concurrently with tremor bursts and LFE signals. Our analysis of continuous data from Costa Rica detected VLF events only when tremor was also occurring, which was only 7% of the total time examined. Using analytic and synthetic models, we show that a cluster of LFE signals produces the distinguishing characteristics of VLF events, which may be determined by the cluster envelope. The envelope may be diagnostic of a single, dynamic, slowly slipping event that propagates coherently over kilometers or represents a narrowly band-passed version of nearly simultaneous arrivals of radiation from slip on multiple higher stress drop and/or faster propagating slip patches with dimensions of tens of meters (i.e., LFE sources). Temporally clustered LFE sources may be triggered by single or multiple distinct aseismic slip events or represent the nearly simultaneous chance occurrence of background LFEs. Given the nonuniqueness in possible source durations, we suggest it is premature to draw conclusions about VLF event sources or how they scale.

Activation of Ras-ERK Signaling and GSK-3 by Amyloid Precursor Protein and Amyloid Beta Facilitates Neurodegeneration in Alzheimer's Disease.

PubMed

Kirouac, Lisa; Rajic, Alexander J; Cribbs, David H; Padmanabhan, Jaya

2017-01-01

It is widely accepted that amyloid β (Aβ) generated from amyloid precursor protein (APP) oligomerizes and fibrillizes to form neuritic plaques in Alzheimer's disease (AD), yet little is known about the contribution of APP to intracellular signaling events preceding AD pathogenesis. The data presented here demonstrate that APP expression and neuronal exposure to oligomeric Aβ42 enhance Ras/ERK signaling cascade and glycogen synthase kinase 3 (GSK-3) activation. We find that RNA interference (RNAi)-directed knockdown of APP in B103 rat neuroblastoma cells expressing APP inhibits Ras-ERK signaling and GSK-3 activation, indicating that APP acts upstream of these signal transduction events. Both ERK and GSK-3 are known to induce hyperphosphorylation of tau and APP at Thr668, and our findings suggest that aberrant signaling by APP facilitates these events. Supporting this notion, analysis of human AD brain samples showed increased expression of Ras, activation of GSK-3, and phosphorylation of APP and tau, which correlated with Aβ levels in the AD brains. Furthermore, treatment of primary rat neurons with Aβ recapitulated these events and showed enhanced Ras-ERK signaling, GSK-3 activation, upregulation of cyclin D1, and phosphorylation of APP and tau. The finding that Aβ induces Thr668 phosphorylation on APP, which enhances APP proteolysis and Aβ generation, denotes a vicious feedforward mechanism by which APP and Aβ promote tau hyperphosphorylation and neurodegeneration in AD. Based on these results, we hypothesize that aberrant proliferative signaling by APP plays a fundamental role in AD neurodegeneration and that inhibition of this would impede cell cycle deregulation and neurodegeneration observed in AD.

Waveform Similarity Analysis: A Simple Template Comparing Approach for Detecting and Quantifying Noisy Evoked Compound Action Potentials.

PubMed

Potas, Jason Robert; de Castro, Newton Gonçalves; Maddess, Ted; de Souza, Marcio Nogueira

2015-01-01

Experimental electrophysiological assessment of evoked responses from regenerating nerves is challenging due to the typical complex response of events dispersed over various latencies and poor signal-to-noise ratio. Our objective was to automate the detection of compound action potential events and derive their latencies and magnitudes using a simple cross-correlation template comparison approach. For this, we developed an algorithm called Waveform Similarity Analysis. To test the algorithm, challenging signals were generated in vivo by stimulating sural and sciatic nerves, whilst recording evoked potentials at the sciatic nerve and tibialis anterior muscle, respectively, in animals recovering from sciatic nerve transection. Our template for the algorithm was generated based on responses evoked from the intact side. We also simulated noisy signals and examined the output of the Waveform Similarity Analysis algorithm with imperfect templates. Signals were detected and quantified using Waveform Similarity Analysis, which was compared to event detection, latency and magnitude measurements of the same signals performed by a trained observer, a process we called Trained Eye Analysis. The Waveform Similarity Analysis algorithm could successfully detect and quantify simple or complex responses from nerve and muscle compound action potentials of intact or regenerated nerves. Incorrectly specifying the template outperformed Trained Eye Analysis for predicting signal amplitude, but produced consistent latency errors for the simulated signals examined. Compared to the trained eye, Waveform Similarity Analysis is automatic, objective, does not rely on the observer to identify and/or measure peaks, and can detect small clustered events even when signal-to-noise ratio is poor. Waveform Similarity Analysis provides a simple, reliable and convenient approach to quantify latencies and magnitudes of complex waveforms and therefore serves as a useful tool for studying evoked compound action potentials in neural regeneration studies.

Waveform Similarity Analysis: A Simple Template Comparing Approach for Detecting and Quantifying Noisy Evoked Compound Action Potentials

PubMed Central

Potas, Jason Robert; de Castro, Newton Gonçalves; Maddess, Ted; de Souza, Marcio Nogueira

2015-01-01

Experimental electrophysiological assessment of evoked responses from regenerating nerves is challenging due to the typical complex response of events dispersed over various latencies and poor signal-to-noise ratio. Our objective was to automate the detection of compound action potential events and derive their latencies and magnitudes using a simple cross-correlation template comparison approach. For this, we developed an algorithm called Waveform Similarity Analysis. To test the algorithm, challenging signals were generated in vivo by stimulating sural and sciatic nerves, whilst recording evoked potentials at the sciatic nerve and tibialis anterior muscle, respectively, in animals recovering from sciatic nerve transection. Our template for the algorithm was generated based on responses evoked from the intact side. We also simulated noisy signals and examined the output of the Waveform Similarity Analysis algorithm with imperfect templates. Signals were detected and quantified using Waveform Similarity Analysis, which was compared to event detection, latency and magnitude measurements of the same signals performed by a trained observer, a process we called Trained Eye Analysis. The Waveform Similarity Analysis algorithm could successfully detect and quantify simple or complex responses from nerve and muscle compound action potentials of intact or regenerated nerves. Incorrectly specifying the template outperformed Trained Eye Analysis for predicting signal amplitude, but produced consistent latency errors for the simulated signals examined. Compared to the trained eye, Waveform Similarity Analysis is automatic, objective, does not rely on the observer to identify and/or measure peaks, and can detect small clustered events even when signal-to-noise ratio is poor. Waveform Similarity Analysis provides a simple, reliable and convenient approach to quantify latencies and magnitudes of complex waveforms and therefore serves as a useful tool for studying evoked compound action potentials in neural regeneration studies. PMID:26325291

A Probabilistic Approach to Network Event Formation from Pre-Processed Waveform Data

NASA Astrophysics Data System (ADS)

Kohl, B. C.; Given, J.

2017-12-01

The current state of the art for seismic event detection still largely depends on signal detection at individual sensor stations, including picking accurate arrivals times and correctly identifying phases, and relying on fusion algorithms to associate individual signal detections to form event hypotheses. But increasing computational capability has enabled progress toward the objective of fully utilizing body-wave recordings in an integrated manner to detect events without the necessity of previously recorded ground truth events. In 2011-2012 Leidos (then SAIC) operated a seismic network to monitor activity associated with geothermal field operations in western Nevada. We developed a new association approach for detecting and quantifying events by probabilistically combining pre-processed waveform data to deal with noisy data and clutter at local distance ranges. The ProbDet algorithm maps continuous waveform data into continuous conditional probability traces using a source model (e.g. Brune earthquake or Mueller-Murphy explosion) to map frequency content and an attenuation model to map amplitudes. Event detection and classification is accomplished by combining the conditional probabilities from the entire network using a Bayesian formulation. This approach was successful in producing a high-Pd, low-Pfa automated bulletin for a local network and preliminary tests with regional and teleseismic data show that it has promise for global seismic and nuclear monitoring applications. The approach highlights several features that we believe are essential to achieving low-threshold automated event detection: Minimizes the utilization of individual seismic phase detections - in traditional techniques, errors in signal detection, timing, feature measurement and initial phase ID compound and propagate into errors in event formation, Has a formalized framework that utilizes information from non-detecting stations, Has a formalized framework that utilizes source information, in particular the spectral characteristics of events of interest, Is entirely model-based, i.e. does not rely on a priori's - particularly important for nuclear monitoring, Does not rely on individualized signal detection thresholds - it's the network solution that matters.

An open source tool for automatic spatiotemporal assessment of calcium transients and local ‘signal-close-to-noise’ activity in calcium imaging data

PubMed Central

Martin, Corinna; Jablonka, Sibylle

2018-01-01

Local and spontaneous calcium signals play important roles in neurons and neuronal networks. Spontaneous or cell-autonomous calcium signals may be difficult to assess because they appear in an unpredictable spatiotemporal pattern and in very small neuronal loci of axons or dendrites. We developed an open source bioinformatics tool for an unbiased assessment of calcium signals in x,y-t imaging series. The tool bases its algorithm on a continuous wavelet transform-guided peak detection to identify calcium signal candidates. The highly sensitive calcium event definition is based on identification of peaks in 1D data through analysis of a 2D wavelet transform surface. For spatial analysis, the tool uses a grid to separate the x,y-image field in independently analyzed grid windows. A document containing a graphical summary of the data is automatically created and displays the loci of activity for a wide range of signal intensities. Furthermore, the number of activity events is summed up to create an estimated total activity value, which can be used to compare different experimental situations, such as calcium activity before or after an experimental treatment. All traces and data of active loci become documented. The tool can also compute the signal variance in a sliding window to visualize activity-dependent signal fluctuations. We applied the calcium signal detector to monitor activity states of cultured mouse neurons. Our data show that both the total activity value and the variance area created by a sliding window can distinguish experimental manipulations of neuronal activity states. Notably, the tool is powerful enough to compute local calcium events and ‘signal-close-to-noise’ activity in small loci of distal neurites of neurons, which remain during pharmacological blockade of neuronal activity with inhibitors such as tetrodotoxin, to block action potential firing, or inhibitors of ionotropic glutamate receptors. The tool can also offer information about local homeostatic calcium activity events in neurites. PMID:29601577

Frequency-Based Precursory Acoustic Emission Failure Sequences In Sedimentary And Igneous Rocks Under Uniaxial Compression

NASA Astrophysics Data System (ADS)

Colin, C.; Anderson, R. C.; Chasek, M. D.; Peters, G. H.; Carey, E. M.

2016-12-01

Identifiable precursors to rock failure have been a long pursued and infrequently encountered phenomena in rock mechanics and acoustic emission studies. Since acoustic emissions in compressed rocks were found to follow the Gutenberg-Richter law, failure-prediction strategies based on temporal changes in b-value have been recurrent. In this study, we extend on the results of Ohnaka and Mogi [Journal of Geophysical Research, Vol. 87, No. B5, p. 3873-3884, (1982)], where the bulk frequency characteristics of rocks under incremental uniaxial compression were observed in relation to changes in b-value before and after failure. Based on the proposition that the number of low-frequency acoustic emissions is proportional to the number of high-amplitude acoustic emissions in compressed rocks, Ohnaka and Mogi (1982) demonstrated that b-value changes in granite and andesite cores under incremental uniaxial compression could be expressed in terms of the percent abundance of low-frequency events. In this study, we attempt to demonstrate that the results of Ohnaka and Mogi (1982) hold true for different rock types (basalt, sandstone, and limestone) and different sample geometries (rectangular prisms). In order to do so, the design of the compression tests was kept similar to that of Ohnaka and Mogi (1982). Two high frequency piezoelectric transducers of 1 MHz and a 500 kHz coupled to the sides of the samples detected higher and lower frequency acoustic emission signals. However, rather than gathering parametric data from an analog signal using a counter as per Ohnaka and Mogi (1982), we used an oscilloscope as an analog to digital converter interfacing with LabVIEW 2015 to record the complete waveforms. The digitally stored waveforms were then processed, detecting acoustic emission events using a statistical method, and filtered using a 2nd order Butterworth filter. In addition to calculating the percent abundance of low-frequency events over time, the peak frequency of the acoustic emissions over time was observable due to the digital method of waveform capture. This allows for a more direct comparison between frequency characteristics and b-values of rocks under compression and investigates the viability of observing frequency behavior over time as a method of rock failure prediction.

Event generators for address event representation transmitters

NASA Astrophysics Data System (ADS)

Serrano-Gotarredona, Rafael; Serrano-Gotarredona, Teresa; Linares Barranco, Bernabe

2005-06-01

Address Event Representation (AER) is an emergent neuromorphic interchip communication protocol that allows for real-time virtual massive connectivity between huge number neurons located on different chips. By exploiting high speed digital communication circuits (with nano-seconds timings), synaptic neural connections can be time multiplexed, while neural activity signals (with mili-seconds timings) are sampled at low frequencies. Also, neurons generate 'events' according to their activity levels. More active neurons generate more events per unit time, and access the interchip communication channel more frequently, while neurons with low activity consume less communication bandwidth. In a typical AER transmitter chip, there is an array of neurons that generate events. They send events to a peripheral circuitry (let's call it "AER Generator") that transforms those events to neurons coordinates (addresses) which are put sequentially on an interchip high speed digital bus. This bus includes a parallel multi-bit address word plus a Rqst (request) and Ack (acknowledge) handshaking signals for asynchronous data exchange. There have been two main approaches published in the literature for implementing such "AER Generator" circuits. They differ on the way of handling event collisions coming from the array of neurons. One approach is based on detecting and discarding collisions, while the other incorporates arbitration for sequencing colliding events . The first approach is supposed to be simpler and faster, while the second is able to handle much higher event traffic. In this article we will concentrate on the second arbiter-based approach. Boahen has been publishing several techniques for implementing and improving the arbiter based approach. Originally, he proposed an arbitration squeme by rows, followed by a column arbitration. In this scheme, while one neuron was selected by the arbiters to transmit his event out of the chip, the rest of neurons in the array were freezed to transmit any further events during this time window. This limited the maximum transmission speed. In order to improve this speed, Boahen proposed an improved 'burst mode' scheme. In this scheme after the row arbitration, a complete row of events is pipelined out of the array and arbitered out of the chip at higher speed. During this single row event arbitration, the array is free to generate new events and communicate to the row arbiter, in a pipelined mode. This scheme significantly improves maximum event transmission speed, specially for high traffic situations were speed is more critical. We have analyzed and studied this approach and have detected some shortcomings in the circuits reported by Boahen, which may render some false situations under some statistical conditions. The present paper proposes some improvements to overcome such situations. The improved "AER Generator" has been implemented in an AER transmitter system

Developmental biology in marine invertebrate symbioses.

PubMed

McFall-Ngai, M J; Ruby, E G

2000-12-01

Associations between marine invertebrates and their cooperative bacterial symbionts offer access to an understanding of the roots of host-microbe interaction; for example, several symbioses like the squid-vibrio light organ association serve as models for investigating how each partner affects the developmental biology of the other. Previous results have identified a program of specific developmental events that unfolds as the association is initiated. In the past year, published studies have focused primarily on describing the mechanisms underlying the signaling processes that occur between the juvenile squid and the luminous bacteria that colonize it.

Influence of ventral tegmental area input on cortico-subcortical networks underlying action control and decision making.

PubMed

Richter, Anja; Gruber, Oliver

2018-02-01

It is argued that the mesolimbic system has a more general function in processing all salient events, including and extending beyond rewards. Saliency was defined as an event that is unexpected due to its frequency of occurrence and elicits an attentional-behavioral switch. Using functional magnetic resonance imaging (fMRI), signals were measured in response to the modulation of salience of rewarding and nonrewarding events during a reward-based decision making task, the so called desire-reason dilemma paradigm (DRD). Replicating previous findings, both frequent and infrequent, and therefore salient, reward stimuli elicited reliable activation of the ventral tegmental area (VTA) and ventral striatum (vStr). When immediate reward desiring contradicted the superordinate task-goal, we found an increased activation of the VTA and vStr when the salient reward stimuli were presented compared to the nonsalient reward stimuli, indicating a boosting of activation in these brain regions. Furthermore, we found a significantly increased functional connectivity between the VTA and vStr, confirming the boosting of vStr activation via VTA input. Moreover, saliency per se without a reward association led to an increased activation of brain regions in the mesolimbic reward system as well as the orbitofrontal cortex (OFC), inferior frontal gyrus (IFG), and anterior cingulate cortex (ACC). Finally, findings uncovered multiple increased functional interactions between cortical saliency-processing brain areas and the VTA and vStr underlying detection and processing of salient events and adaptive decision making. © 2017 Wiley Periodicals, Inc.

40 CFR 86.1370-2007 - Not-To-Exceed test procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... that include discrete regeneration events and that send a recordable electronic signal indicating the start and end of the regeneration event, determine the minimum averaging period for each NTE event that... averaging period is used to determine whether the individual NTE event is a valid NTE event. For engines...

Monoamines stimulate sex reversal in the saddleback wrasse.

PubMed

Larson, Earl T; Norris, David O; Gordon Grau, E; Summers, Cliff H

2003-02-15

Monoamine neurotransmitters (norepinephrine, dopamine, and serotonin) play an important role in reproduction and sexual behavior throughout the vertebrates. They are the first endogenous chemical signals in the regulation of the hypothalamo-pituitary-gonadal (HPG) axis. In teleosts with behavioral sex determination, much is known about behavioral cues that induce sex reversal. The cues are social, processed via the visual system and depend on the ratio of females to males in the population. The mechanisms by which these external behavioral cues are converted to an internal chemical regulatory process are largely unknown. The protogynous Hawaiian saddleback wrasse, Thalassoma duperrey, was used to investigate the biological pathway mediating the conversion of a social cue into neuroendocrine events regulating sex reversal. Because monoamines play an important role in the regulation of the HPG axis, they were selected as likely candidates for such a conversion. To determine if monoamines could affect sex reversal, drugs affecting monoamines were used in an attempt to either induce sex reversal under non-permissive conditions, or prevent sex reversal under permissive conditions. Increasing norepinephrine or blocking dopamine or serotonin lead to sex reversal in experimental animals under non-permissive conditions. Increasing serotonin blocked sex reversal under permissive conditions, while blocking dopamine or norepinephrine retarded the process. The results presented here demonstrate that monoamines contribute significantly to the control sex reversal. Norepinephrine stimulates initiation and completion of gonadal sex of reversal as well as color change perhaps directly via its effects on the HPG axis. Dopamine exercises inhibitory action on the initiation of sex reversal while 5-HT inhibits both initiation and completion of sex reversal. The serotonergic system appears to be an integral part of the pathway mediating the conversion of a social cue into a neuroendocrine event. The complex organization of neurochemical events controlling the psychosocial, physiological, and anatomical events that constitute reversal of sexual identity includes monoamine neurotransmitters. Copyright 2003 Elsevier Science (USA)

Gene Expression Networks Underlying Ovarian Development in Wild Largemouth Bass (Micropterus salmoides)

PubMed Central

Martyniuk, Christopher J.; Prucha, Melinda S.; Doperalski, Nicholas J.; Antczak, Philipp; Kroll, Kevin J.; Falciani, Francesco; Barber, David S.; Denslow, Nancy D.

2013-01-01

Background Oocyte maturation in fish involves numerous cell signaling cascades that are activated or inhibited during specific stages of oocyte development. The objectives of this study were to characterize molecular pathways and temporal gene expression patterns throughout a complete breeding cycle in wild female largemouth bass to improve understanding of the molecular sequence of events underlying oocyte maturation. Methods Transcriptomic analysis was performed on eight morphologically diverse stages of the ovary, including primary and secondary stages of oocyte growth, ovulation, and atresia. Ovary histology, plasma vitellogenin, 17β-estradiol, and testosterone were also measured to correlate with gene networks. Results Global expression patterns revealed dramatic differences across ovarian development, with 552 and 2070 genes being differentially expressed during both ovulation and atresia respectively. Gene set enrichment analysis (GSEA) revealed that early primary stages of oocyte growth involved increases in expression of genes involved in pathways of B-cell and T-cell receptor-mediated signaling cascades and fibronectin regulation. These pathways as well as pathways that included adrenergic receptor signaling, sphingolipid metabolism and natural killer cell activation were down-regulated at ovulation. At atresia, down-regulated pathways included gap junction and actin cytoskeleton regulation, gonadotrope and mast cell activation, and vasopressin receptor signaling and up-regulated pathways included oxidative phosphorylation and reactive oxygen species metabolism. Expression targets for luteinizing hormone signaling were low during vitellogenesis but increased 150% at ovulation. Other networks found to play a significant role in oocyte maturation included those with genes regulated by members of the TGF-beta superfamily (activins, inhibins, bone morphogenic protein 7 and growth differentiation factor 9), neuregulin 1, retinoid X receptor, and nerve growth factor family. Conclusions This study offers novel insight into the gene networks underlying vitellogenesis, ovulation and atresia and generates new hypotheses about the cellular pathways regulating oocyte maturation. PMID:23527095

Experimental investigations of OSL signal changes of quartz gouge during low- to high-velocity friction

NASA Astrophysics Data System (ADS)

Oohashi, K.; Akasegawa, K.; Hasebe, N.; Miura, K.; Minomo, Y.

2017-12-01

Luminescence dating methods such as OSL and TL are mainly used to characterize an age of sediments based on trapping of electron by natural radiation exposure. Recent research suggests its potential applicability for direct age measurement of faulting. The idea behind to the luminescence dating for a determination of paleo-earthquake event is the accumulated natural radiation damage in intra-fault materials becomes to zero by the frictional heating and/or grinding. However, a relationship between fault motion and annihilation of luminescence signals, and its mechanism has not been understood. In this study, we conduct low- to high-velocity friction experiments using quartz gouge under various displacements and moisture conditions to establish an empirical relationship of OSL signal change upon shearing. In the friction experiments, we used quartz grains of <150 μm separated from the Cretaceous granite, taken from the east wall of the Nojima fault Ogura trench site, western Japan, as an analogue gouge. Our results of the OSL measurements are (1) <75 μm fraction of sheared gouge have high fast component ratio than the pre-sheared grains, (2) the fast component ratio of <75 μm fraction increases with increasing slip rate from 200 μm/s to 0.13 m, (3) OSL signal becomes to zero in the experiment sheared under 0.65 m/s. The increase of the fast component ratio found in relatively low slip-rate experiments may be caused by addition of ionized electrons, that emitted from newly formed fracture surface during comminution, in electron center. The signal zeroing observed in the high-velocity friction experiment is attributable to rapid frictional heating up to 700 °C estimated by temperature measurement and calculation. Based on the calculation of frictional energy we added to the experiment sheared under 0.65 m/s, we estimated the zeroing depth in natural conditions of earthquake (1.6 m in displacement) to 192 m.

Multi-purpose ECG telemetry system.

PubMed

Marouf, Mohamed; Vukomanovic, Goran; Saranovac, Lazar; Bozic, Miroslav

2017-06-19

The Electrocardiogram ECG is one of the most important non-invasive tools for cardiac diseases diagnosis. Taking advantage of the developed telecommunication infrastructure, several approaches that address the development of telemetry cardiac devices were introduced recently. Telemetry ECG devices allow easy and fast ECG monitoring of patients with suspected cardiac issues. Choosing the right device with the desired working mode, signal quality, and the device cost are still the main obstacles to massive usage of these devices. In this paper, we introduce design, implementation, and validation of a multi-purpose telemetry system for recording, transmission, and interpretation of ECG signals in different recording modes. The system consists of an ECG device, a cloud-based analysis pipeline, and accompanied mobile applications for physicians and patients. The proposed ECG device's mechanical design allows laypersons to easily record post-event short-term ECG signals, using dry electrodes without any preparation. Moreover, patients can use the device to record long-term signals in loop and holter modes, using wet electrodes. In order to overcome the problem of signal quality fluctuation due to using different electrodes types and different placements on subject's chest, customized ECG signal processing and interpretation pipeline is presented for each working mode. We present the evaluation of the novel short-term recorder design. Recording of an ECG signal was performed for 391 patients using a standard 12-leads golden standard ECG and the proposed patient-activated short-term post-event recorder. In the validation phase, a sample of validation signals followed peer review process wherein two experts annotated the signals in terms of signal acceptability for diagnosis.We found that 96% of signals allow detecting arrhythmia and other signal's abnormal changes. Additionally, we compared and presented the correlation coefficient and the automatic QRS delineation results of both short-term post-event recorder and 12-leads golden standard ECG recorder. The proposed multi-purpose ECG device allows physicians to choose the working mode of the same device according to the patient status. The proposed device was designed to allow patients to manage the technical requirements of both working modes. Post-event short-term ECG recording using the proposed design provide physicians reliable three ECG leads with direct symptom-rhythm correlation.

Heterogeneous Intracellular Trafficking Dynamics of Brain-Derived Neurotrophic Factor Complexes in the Neuronal Soma Revealed by Single Quantum Dot Tracking

PubMed Central

Vermehren-Schmaedick, Anke; Krueger, Wesley; Jacob, Thomas; Ramunno-Johnson, Damien; Balkowiec, Agnieszka; Lidke, Keith A.; Vu, Tania Q.

2014-01-01

Accumulating evidence underscores the importance of ligand-receptor dynamics in shaping cellular signaling. In the nervous system, growth factor-activated Trk receptor trafficking serves to convey biochemical signaling that underlies fundamental neural functions. Focus has been placed on axonal trafficking but little is known about growth factor-activated Trk dynamics in the neuronal soma, particularly at the molecular scale, due in large part to technical hurdles in observing individual growth factor-Trk complexes for long periods of time inside live cells. Quantum dots (QDs) are intensely fluorescent nanoparticles that have been used to study the dynamics of ligand-receptor complexes at the plasma membrane but the value of QDs for investigating ligand-receptor intracellular dynamics has not been well exploited. The current study establishes that QD conjugated brain-derived neurotrophic factor (QD-BDNF) binds to TrkB receptors with high specificity, activates TrkB downstream signaling, and allows single QD tracking capability for long recording durations deep within the soma of live neurons. QD-BDNF complexes undergo internalization, recycling, and intracellular trafficking in the neuronal soma. These trafficking events exhibit little time-synchrony and diverse heterogeneity in underlying dynamics that include phases of sustained rapid motor transport without pause as well as immobility of surprisingly long-lasting duration (several minutes). Moreover, the trajectories formed by dynamic individual BDNF complexes show no apparent end destination; BDNF complexes can be found meandering over long distances of several microns throughout the expanse of the neuronal soma in a circuitous fashion. The complex, heterogeneous nature of neuronal soma trafficking dynamics contrasts the reported linear nature of axonal transport data and calls for models that surpass our generally limited notions of nuclear-directed transport in the soma. QD-ligand probes are poised to provide understanding of how the molecular mechanisms underlying intracellular ligand-receptor trafficking shape cell signaling under conditions of both healthy and dysfunctional neurological disease models. PMID:24732948

Heat stress differentially modifies ethylene biosynthesis and signaling in pea floral and fruit tissues.

PubMed

Savada, Raghavendra P; Ozga, Jocelyn A; Jayasinghege, Charitha P A; Waduthanthri, Kosala D; Reinecke, Dennis M

2017-10-01

Ethylene biosynthesis is regulated in reproductive tissues in response to heat stress in a manner to optimize resource allocation to pollinated fruits with developing seeds. High temperatures during reproductive development are particularly detrimental to crop fruit/seed production. Ethylene plays vital roles in plant development and abiotic stress responses; however, little is known about ethylene's role in reproductive tissues during development under heat stress. We assessed ethylene biosynthesis and signaling regulation within the reproductive and associated tissues of pea during the developmental phase that sets the stage for fruit-set and seed development under normal and heat-stress conditions. The transcript abundance profiles of PsACS [encode enzymes that convert S-adenosyl-L-methionine to 1-aminocyclopropane-1-carboxylic acid (ACC)] and PsACO (encode enzymes that convert ACC to ethylene), and ethylene evolution were developmentally, environmentally, and tissue-specifically regulated in the floral/fruit/pedicel tissues of pea. Higher transcript abundance of PsACS and PsACO in the ovaries, and PsACO in the pedicels was correlated with higher ethylene evolution and ovary senescence and pedicel abscission in fruits that were not pollinated under control temperature conditions. Under heat-stress conditions, up-regulation of ethylene biosynthesis gene expression in pre-pollinated ovaries was also associated with higher ethylene evolution and lower retention of these fruits. Following successful pollination and ovule fertilization, heat-stress modified PsACS and PsACO transcript profiles in a manner that suppressed ovary ethylene evolution. The normal ethylene burst in the stigma/style and petals following pollination was also suppressed by heat-stress. Transcript abundance profiles of ethylene receptor and signaling-related genes acted as qualitative markers of tissue ethylene signaling events. These data support the hypothesis that ethylene biosynthesis is regulated in reproductive tissues in response to heat stress to modulate resource allocation dynamics.

A Search for WIMP Dark Matter Using an Optimized Chi-square Technique on the Final Data from the Cryogenic Dark Matter Search Experiment (CDMS II)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manungu Kiveni, Joseph

2012-12-01

This dissertation describes the results of a WIMP search using CDMS II data sets accumulated at the Soudan Underground Laboratory in Minnesota. Results from the original analysis of these data were published in 2009; two events were observed in the signal region with an expected leakage of 0.9 events. Further investigation revealed an issue with the ionization-pulse reconstruction algorithm leading to a software upgrade and a subsequent reanalysis of the data. As part of the reanalysis, I performed an advanced discrimination technique to better distinguish (potential) signal events from backgrounds using a 5-dimensional chi-square method. This dataanalysis technique combines themore » event information recorded for each WIMP-search event to derive a backgrounddiscrimination parameter capable of reducing the expected background to less than one event, while maintaining high efficiency for signal events. Furthermore, optimizing the cut positions of this 5-dimensional chi-square parameter for the 14 viable germanium detectors yields an improved expected sensitivity to WIMP interactions relative to previous CDMS results. This dissertation describes my improved (and optimized) discrimination technique and the results obtained from a blind application to the reanalyzed CDMS II WIMP-search data.« less

Automated electrohysterographic detection of uterine contractions for monitoring of pregnancy: feasibility and prospects.

PubMed

Muszynski, C; Happillon, T; Azudin, K; Tylcz, J-B; Istrate, D; Marque, C

2018-05-08

Preterm birth is a major public health problem in developed countries. In this context, we have conducted research into outpatient monitoring of uterine electrical activity in women at risk of preterm delivery. The objective of this preliminary study was to perform automated detection of uterine contractions (without human intervention or tocographic signal, TOCO) by processing the EHG recorded on the abdomen of pregnant women. The feasibility and accuracy of uterine contraction detection based on EHG processing were tested and compared to expert decision using external tocodynamometry (TOCO) . The study protocol was approved by local Ethics Committees under numbers ID-RCB 2016-A00663-48 for France and VSN 02-0006-V2 for Iceland. Two populations of women were included (threatened preterm birth and labour) in order to test our system of recognition of the various types of uterine contractions. EHG signal acquisition was performed according to a standardized protocol to ensure optimal reproducibility of EHG recordings. A system of 18 Ag/AgCl surface electrodes was used by placing 16 recording electrodes between the woman's pubis and umbilicus according to a 4 × 4 matrix. TOCO was recorded simultaneously with EHG recording. EHG signals were analysed in real-time by calculation of the nonlinear correlation coefficient H 2 . A curve representing the number of correlated pairs of signals according to the value of H 2 calculated between bipolar signals was then plotted. High values of H 2 indicated the presence of an event that may correspond to a contraction. Two tests were performed after detection of an event (fusion and elimination of certain events) in order to increase the contraction detection rate. The EHG database contained 51 recordings from pregnant women, with a total of 501 contractions previously labelled by analysis of the corresponding tocographic recording. The percentage recognitions obtained by application of the method based on coefficient H 2 was 100% with 782% of false alarms. Addition of fusion and elimination tests to the previously obtained detections allowed the false alarm rate to be divided by 8.5, while maintaining an excellent detection rate (96%). These preliminary results appear to be encouraging for monitoring of uterine contractions by algorithm-based automated detection to process the electrohysterographic signal (EHG). This compact recording system, based on the use of surface electrodes attached to the skin, appears to be particularly suitable for outpatient monitoring of uterine contractions, possibly at home, allowing telemonitoring of pregnancies. One of the advantages of EHG processing is that useful information concerning contraction efficiency can be extracted from this signal, which is not possible with the TOCO signal.

Signals of El Niño Modoki in the tropical tropopause layer and stratosphere

NASA Astrophysics Data System (ADS)

Xie, F.; Li, J.; Tian, W.; Feng, J.; Huo, Y.

2012-06-01

The effects of El Niño Modoki events on the tropical tropopause layer (TTL) and on the stratosphere were investigated using European Center for Medium Range Weather Forecasting (ECMWF) reanalysis data, oceanic El Niño indices, and general climate model outputs. El Niño Modoki events tend to depress convective activities in the western and eastern Pacific but enhance convective activities in the central and northern Pacific. Consequently, during El Niño Modoki events, negative water vapor anomalies occur in the western and eastern Pacific upper troposphere, whereas there are positive anomalies in the central and northern Pacific upper troposphere. The spatial patterns of the outgoing longwave radiation (OLR) and upper tropospheric water vapor anomalies exhibit a tripolar form. The empirical orthogonal function (EOF) analysis of the OLR and upper tropospheric water vapor anomalies reveals that canonical El Niño events are associated with the leading mode of the EOF, while El Niño Modoki events correspond to the second mode. The composite analysis based on ERA-interim data indicate that El Niño Modoki events have a reverse effect on middle-high latitudes stratosphere, as compared with the effect of typical El Niño events, i.e., the northern polar vortex is stronger and colder but the southern polar vortex is weaker and warmer during El Niño Modoki events. According to the simulation' results, we found that the reverse effect on the middle-high latitudes stratosphere is resulted from a complicated interaction between quasi-biennial oscillation (QBO) signal of east phase and El Niño Modoki signal. This interaction is not a simply linear overlay of QBO signal and El Niño Modoki signal in the stratosphere, it is El Niño Modoki that leads to different tropospheric zonal wind anomalies with QBO forcing from that caused by typical El Niño, thus, the planetary wave propagation from troposphere to the stratosphere during El Niño Modoki events is different from that during canonical El Niño events. However, when QBO is in its west phase, El Niño Modoki events have the same effect on middle-high latitudes stratosphere as the typical El Niño events. Our simulations also suggest that canonical El Niño and El Niño Modoki activities actually have the same influence on the middle-high latitudes stratosphere when in the absence of QBO forcing.

Phospho-control of TGF-β superfamily signaling

PubMed Central

Wrighton, Katharine H; Lin, Xia; Feng, Xin-Hua

2010-01-01

Members of the transforming growth factor-β (TGF-β) family control a broad range of cellular responses in metazoan organisms via autocrine, paracrine, and endocrine modes. Thus, aberrant TGF-β signaling can play a key role in the pathogenesis of several diseases, including cancer. TGF-β signaling pathways are activated by a short phospho-cascade, from receptor phosphorylation to the subsequent phosphorylation and activation of downstream signal transducers called R-Smads. R-Smad phosphorylation state determines Smad complex assembly/disassembly, nuclear import/export, transcriptional activity and stability, and is thus the most critical event in TGF-β signaling. Dephosphorylation of R-Smads by specific phosphatases prevents or terminates TGF-β signaling, highlighting the need to consider Smad (de)phosphorylation as a tightly controlled and dynamic event. This article illustrates the essential roles of reversible phosphorylation in controlling the strength and duration of TGF-β signaling and the ensuing physiological responses. PMID:19114991

Optical recording of action potentials and other discrete physiological events: a perspective from signal detection theory.

PubMed

Sjulson, Lucas; Miesenböck, Gero

2007-02-01

Optical imaging of physiological events in real time can yield insights into biological function that would be difficult to obtain by other experimental means. However, the detection of all-or-none events, such as action potentials or vesicle fusion events, in noisy single-trial data often requires a careful balance of tradeoffs. The analysis of such experiments, as well as the design of optical reporters and instrumentation for them, is aided by an understanding of the principles of signal detection. This review illustrates these principles, using as an example action potential recording with optical voltage reporters.

Signals of El Niño Modoki in the tropical tropopause layer and stratosphere

NASA Astrophysics Data System (ADS)

Xie, F.; Li, J.; Tian, W.; Feng, J.

2012-02-01

The effects of El Niño Modoki events on the tropical tropopause layer (TTL) and on the stratosphere were investigated using European Center for Medium Range Weather Forecasting (ECMWF) reanalysis data, satellite observations from the Aura satellite Microwave Limb Sounder (MLS), oceanic El Niño indices, and general climate model outputs. El Niño Modoki events tend to depress convective activities in the western and eastern Pacific but enhance convective activities in the central and northern Pacific. Consequently, during Modoki events, negative water vapor anomalies occur in the western and eastern Pacific upper troposphere, whereas there are positive anomalies in the central and northern Pacific upper troposphere. The spatial patterns of the outgoing longwave radiation (OLR) and upper tropospheric water vapor anomalies exhibit a tripolar form. The empirical orthogonal function (EOF) analysis of the OLR and upper tropospheric water vapor anomalies reveals that canonical El Niño events are associated with the leading mode of the EOF, while El Niño Modoki events correspond to the second mode. El Niño Modoki activities tend to moisten the lower and middle stratosphere, but dry the upper stratosphere. It was also found that the canonical El Niño signal can overlay linearly on the QBO signal in the stratosphere, whereas the interaction between the El Niño Modoki and QBO signals is non-linear. Because of these non-linear interactions, El Niño Modoki events have a reverse effect on high latitudes stratosphere, as compared with the effects of typical Modoki events, i.e. the northern polar vortex is stronger and colder but the southern polar vortex is weaker and warmer during El Niño Modoki events. However, simulations suggest that canonical El Niño and El Niño Modoki activities actually have the same influence on high latitudes stratosphere, in the absence of interactions between QBO and ENSO signals. The present results also reveal that canonical El Niño events have a greater impact on the high-latitude Northern Hemisphere stratosphere than on the high-latitude Southern Hemisphere stratosphere. However, El Niño Modoki events can more profoundly influence the high-latitude Southern Hemisphere stratosphere than the high-latitude Northern Hemisphere stratosphere.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Endele, Max; Etzrodt, Martin; Schroeder, Timm, E-mail: timm.schroeder@bsse.ethz.ch

Hematopoiesis is the cumulative consequence of finely tuned signaling pathways activated through extrinsic factors, such as local niche signals and systemic hematopoietic cytokines. Whether extrinsic factors actively instruct the lineage choice of hematopoietic stem and progenitor cells or are only selectively allowing survival and proliferation of already intrinsically lineage-committed cells has been debated over decades. Recent results demonstrated that cytokines can instruct lineage choice. However, the precise function of individual cytokine-triggered signaling molecules in inducing cellular events like proliferation, lineage choice, and differentiation remains largely elusive. Signal transduction pathways activated by different cytokine receptors are highly overlapping, but support themore » production of distinct hematopoietic lineages. Cellular context, signaling dynamics, and the crosstalk of different signaling pathways determine the cellular response of a given extrinsic signal. New tools to manipulate and continuously quantify signaling events at the single cell level are therefore required to thoroughly interrogate how dynamic signaling networks yield a specific cellular response. - Highlights: • Recent studies provided definite proof for lineage-instructive action of cytokines. • Signaling pathways involved in hematopoietic lineage instruction remain elusive. • New tools are emerging to quantitatively study dynamic signaling networks over time.« less

Cargo-mediated regulation of a rapid Rab4-dependent recycling pathway.

PubMed

Yudowski, Guillermo A; Puthenveedu, Manojkumar A; Henry, Anastasia G; von Zastrow, Mark

2009-06-01

Membrane trafficking is well known to regulate receptor-mediated signaling processes, but less is known about whether signaling receptors conversely regulate the membrane trafficking machinery. We investigated this question by focusing on the beta-2 adrenergic receptor (B2AR), a G protein-coupled receptor whose cellular signaling activity is controlled by ligand-induced endocytosis followed by recycling. We used total internal reflection fluorescence microscopy (TIR-FM) and tagging with a pH-sensitive GFP variant to image discrete membrane trafficking events mediating B2AR endo- and exocytosis. Within several minutes after initiating rapid endocytosis of B2ARs by the adrenergic agonist isoproterenol, we observed bright "puffs" of locally increased surface fluorescence intensity representing discrete Rab4-dependent recycling events. These events reached a constant frequency in the continuous presence of isoproterenol, and agonist removal produced a rapid (observed within 1 min) and pronounced (approximately twofold) increase in recycling event frequency. This regulation required receptor signaling via the cAMP-dependent protein kinase (PKA) and a specific PKA consensus site located in the carboxyl-terminal cytoplasmic tail of the B2AR itself. B2AR-mediated regulation was not restricted to this membrane cargo, however, as transferrin receptors packaged in the same population of recycling vesicles were similarly affected. In contrast, net recycling measured over a longer time interval (10 to 30 min) was not detectably regulated by B2AR signaling. These results identify rapid regulation of a specific recycling pathway by a signaling receptor cargo.

Evaluation of Position Resolution for a Prototype Whole-Body PET Detector Based on Suppressing Backgrounds by Compton Scattering

NASA Astrophysics Data System (ADS)

Fujihara, Kento; Emoto, Yusaku; Ito, Hiroshi; Kaneko, Naomi; Kaneko, Hideyuki; Kawai, Hideyuki; Kobayashi, Atsushi; Mizuno, Takahiro

2018-01-01

Existing PET (Positron Emission Tomography) systems make clear images in demonstration (measuring small PET reagent in pure water), however images in real diagnosis become unclear. The authors suspected that this problem was caused by Compton scattering in a detector. When PET systems observe plural photomultiplier tube outputs, an original emission point is regarded as centroid of the outputs. However, even if plural emission in Compton scattering occur, these systems calculate original point in the same way as single emission. Therefore, the authors considered that rejecting Compton scattering events makes PET systems much better, and made prototype counter. Main components of the prototype counter are plate-like high-growth-rate (HGR) La-GPS scintillators and wavelength shifting fibers (WLSF). HGR crystals grow 10 times as fast as a mono-crystal (a normal mono-crystal grows at 2 - 3 mm an hour). Thus, it includes microbubble and its transparency get worth. Consequently, HGR crystals usually are not used in radiation measuring instruments. However, this time they are used on the purpose. Because of their low transparency, scintillation lights come out right above and right under of emission position. Therefore, Compton scattering events is rejected easily. The prototype detector has an effective area of 300 by 300 square mm. The detector consists of 24 layers. One layer consists of HGR La-GPS scintillator of 1 mm thickness. Top and bottom surface of scintillator were covered by dual sheets of WLSF with a diameter of 0.2 mm. Sheets of WLSF on top and bottom of the scintillator make a right angle with each other, and measure X- and Y-components. Z-component is measured by difference of WLSF outputs between top and bottom. If plural layers output signals, this counter regards the event as Compton scattering event, and reject the event. Even if only a layer output signals, the event is rejected when number output signals from WLSF is more than 1.5 times of single emission. Material cost of this system is, 0.2M for HGR La-GPS, 0.03M for WLSF, 0.03M for 600 units of 6 by 6 mm SiPM's, 0.12M for 12000 units of 1 by 1 mm SiPM's, and 0.09M for 1800 channel of signal readout circuits. Considering total cost, price of this PET will be set 1M or less. This idea was confirmed with numerical simulation and experimentation. In experimentation, position resolution in photoelectric absorption was 0.2 mm, and minimum distance that this detector could recognize plural emission in Compton scattering was 1 mm. In parallel, three kinds of model were made: a prototype detector, all the signals readout method, and resistance delay method. Simulation setting was 2 MBq/L in normal tissue and 10 MBq/L in cancer. As a result of simulation, a prototype detector identified 3 mm cancer, however the others made unclear image and was not able to identified cancer. That is to say, the prototype detector is able to reject Compton scattering events and inexpensive. Therefore, whole-body PET system with this detector must diagnose cancer with a diameter of 3 mm or more and be priced 1M or less

The LDL Receptor-Related Protein 1 (LRP1) Regulates the PDGF Signaling Pathway by Binding the Protein Phosphatase SHP-2 and Modulating SHP-2- Mediated PDGF Signaling Events

PubMed Central

Craig, Julie; Mikhailenko, Irina; Noyes, Nathaniel; Migliorini, Mary; Strickland, Dudley K.

2013-01-01

Background The PDGF signaling pathway plays a major role in several biological systems, including vascular remodeling that occurs following percutaneous transluminal coronary angioplasty. Recent studies have shown that the LDL receptor-related protein 1 (LRP1) is a physiological regulator of the PDGF signaling pathway. The underlying mechanistic details of how this regulation occurs have yet to be resolved. Activation of the PDGF receptor β (PDGFRβ) leads to tyrosine phosphorylation of the LRP1 cytoplasmic domain within endosomes and generates an LRP1 molecule with increased affinity for adaptor proteins such as SHP-2 that are involved in signaling pathways. SHP-2 is a protein tyrosine phosphatase that positively regulates the PDGFRβ pathway, and is required for PDGF-mediated chemotaxis. We investigated the possibility that LRP1 may regulate the PDGFRβ signaling pathway by binding SHP-2 and competing with the PDGFRβ for this molecule. Methodology/Principal Findings To quantify the interaction between SHP-2 and phosphorylated forms of the LRP1 intracellular domain, we utilized an ELISA with purified recombinant proteins. These studies revealed high affinity binding of SHP-2 to phosphorylated forms of both LRP1 intracellular domain and the PDGFRβ kinase domain. By employing the well characterized dynamin inhibitor, dynasore, we established that PDGF-induced SHP-2 phosphorylation primarily occurs within endosomal compartments, the same compartments in which LRP1 is tyrosine phosphorylated by activated PDGFRβ. Immunofluorescence studies revealed colocalization of LRP1 and phospho-SHP-2 following PDGF stimulation of fibroblasts. To define the contribution of LRP1 to SHP-2-mediated PDGF chemotaxis, we employed fibroblasts expressing LRP1 and deficient in LRP1 and a specific SHP-2 inhibitor, NSC-87877. Our results reveal that LRP1 modulates SHP-2-mediated PDGF-mediated chemotaxis. Conclusions/Significance Our data demonstrate that phosphorylated forms of LRP1 and PDGFRβ compete for SHP-2 binding, and that expression of LRP1 attenuates SHP-2-mediated PDGF signaling events. PMID:23922991

The GNSS polarimetric radio-occultation technique to sense precipitation events: a new concept to be tested aboard PAZ Low Earth Satellite

NASA Astrophysics Data System (ADS)

Tomás, Sergio; Oliveras, Santi; Cardellach, Estel; Rius, Antonio

2013-04-01

The Radio Occultation and Heavy Precipitation (ROHP) experiment, to be conducted aboard the Spanish PAZ satellite, consists of a radio occultation (RO) mission provided with dual-polarization capabilities. The research with polarimetric RO data has the goal of assessing the capabilities and limitations of this technique to infer profiles of heavy precipitation. The technique aims to provide vertical profiles of precipitation simultaneously to the vertical profiles of thermodynamic parameters (standard RO products) perfectly collocated both in space and time. If successful, the polarimetric RO will represent the first technique able to provide these complementary information on precipitation. This is a relevant input for studies on heavy and violent rainfall events, which being poorly represented by the current-generation of Numerical Weather Prediction and General Circulation Models appear to be difficult to forecast on all time-scales. The Low Earth Orbiter hosting this experiment, to be launched in 2013, will orbit at 500 km altitude in a near-Polar orbit. The Radio Occulation payload includes a RO GNSS receiver and a dual polarization (H/V) limb oriented antenna to capture the signals of setting GNSS transmitters. NOAA and UCAR participate in the ground-segment of the radiometric experiment to enable near-real time dissemination of the level-1 standard RO products. The space-based GNSS RO technique scans the atmosphere vertically at fine resolution (close to 300 meter in the troposphere) by precisely measure the delay between a GNSS transmitter and a GNSS receiver aboard a Low Earth Orbiter, when the former is setting below or rising above the Earth limb. The standard, thermodynamical, products are extracted from the excess delay induced by the atmosphere at different layers. This presentation will not focus on this well-established application, but a novel concept using polarimetry to also retrieve rain information. The precipitation-measurement principle is based on the asymmetry between the vertical and horizontal axis of the rain droplets, especially when intense rates of precipitation occur. As a first approximation, the RO signals propagate across the precipitation-volume tangentially, that is, along the local horizontal axis of the droplets. Forward scattering models have been implemented to quantify the sensitivity of L-band signals to different rain rates and precipitation extension being crossed by the signals. The observable considered so far is the polarimetric phase shift: difference between the phase delay suffered by the H- and V-polarizations. Real RO events have been collocated with TRMM precipitation data. The path traveled by the RO signal under a given altitude has been projected on the TRMM grid of observations, to obtain a profile of the precipitation being crossed by the RO link at a given moment of the occultation event. This mechanism has been used to feed the propagation models and thus estimate the polarimetric phase shift that each precipitation event would have induced into the occultation observation. This simulation exercise permits to determine the detectability thresholds and the expected statistics of such collocated events. Methodology and results will be presented.

Distributed cable sensors with memory feature for post-disaster damage assessment

NASA Astrophysics Data System (ADS)

Chen, Genda; McDaniel, Ryan D.; Pommerenke, David J.; Sun, Shishuang

2005-05-01

A new design of distributed crack sensors is presented for the condition assessment of reinforced concrete (RC) structures during and immediately after an earthquake event. This study is mainly focused on the performance of cable sensors under dynamic loading, particularly their ability to memorize the crack history of an RC member. This unique memory feature enables the post-earthquake condition assessment of structural members such as RC columns, in which the earthquake-induced cracks are closed immediately after an earthquake event due to gravity loads and they are visually undetectable. Factors affecting the onset of the memory feature were investigated experimentally with small-scale RC beams under cyclic loading. Test results indicated that both crack width and the number of loading cycles were instrumental in the onset of the memory feature of cable sensors. Practical issues related to dynamic acquisition with the sensors were discussed. The sensors were proven to be fatigue resistant from the shake table tests of RC columns. They continued to show useful signal after the columns can no longer support additional loads.

Analysis of Ribosome Stalling and Translation Elongation Dynamics by Deep Learning.

PubMed

Zhang, Sai; Hu, Hailin; Zhou, Jingtian; He, Xuan; Jiang, Tao; Zeng, Jianyang

2017-09-27

Ribosome stalling is manifested by the local accumulation of ribosomes at specific codon positions of mRNAs. Here, we present ROSE, a deep learning framework to analyze high-throughput ribosome profiling data and estimate the probability of a ribosome stalling event occurring at each genomic location. Extensive validation tests on independent data demonstrated that ROSE possessed higher prediction accuracy than conventional prediction models, with an increase in the area under the receiver operating characteristic curve by up to 18.4%. In addition, genome-wide statistical analyses showed that ROSE predictions can be well correlated with diverse putative regulatory factors of ribosome stalling. Moreover, the genome-wide ribosome stalling landscapes of both human and yeast computed by ROSE recovered the functional interplays between ribosome stalling and cotranslational events in protein biogenesis, including protein targeting by the signal recognition particles and protein secondary structure formation. Overall, our study provides a novel method to complement the ribosome profiling techniques and further decipher the complex regulatory mechanisms underlying translation elongation dynamics encoded in the mRNA sequence. Copyright © 2017 Elsevier Inc. All rights reserved.

Microtubule bundling plays a role in ethylene-mediated cortical microtubule reorientation in etiolated Arabidopsis hypocotyls.

PubMed

Ma, Qianqian; Sun, Jingbo; Mao, Tonglin

2016-05-15

The gaseous hormone ethylene is known to regulate plant growth under etiolated conditions (the 'triple response'). Although organization of cortical microtubules is essential for cell elongation, the underlying mechanisms that regulate microtubule organization by hormone signaling, including ethylene, are ambiguous. In the present study, we demonstrate that ethylene signaling participates in regulation of cortical microtubule reorientation. In particular, regulation of microtubule bundling is important for this process in etiolated hypocotyls. Time-lapse analysis indicated that selective stabilization of microtubule-bundling structures formed in various arrays is related to ethylene-mediated microtubule orientation. Bundling events and bundle growth lifetimes were significantly increased in oblique and longitudinal arrays, but decreased in transverse arrays in wild-type cells in response to ethylene. However, the effects of ethylene on microtubule bundling were partially suppressed in a microtubule-bundling protein WDL5 knockout mutant (wdl5-1). This study suggests that modulation of microtubule bundles that have formed in certain orientations plays a role in reorienting microtubule arrays in response to ethylene-mediated etiolated hypocotyl cell elongation. © 2016. Published by The Company of Biologists Ltd.

CTR1 phosphorylates the central regulator EIN2 to control ethylene hormone signaling from the ER membrane to the nucleus in Arabidopsis

PubMed Central

Ju, Chuanli; Yoon, Gyeong Mee; Shemansky, Jennifer Marie; Lin, David Y.; Ying, Z. Irene; Chang, Jianhong; Garrett, Wesley M.; Kessenbrock, Mareike; Groth, Georg; Tucker, Mark L.; Cooper, Bret; Kieber, Joseph J.; Chang, Caren

2012-01-01

The gaseous phytohormone ethylene C2H4 mediates numerous aspects of growth and development. Genetic analysis has identified a number of critical elements in ethylene signaling, but how these elements interact biochemically to transduce the signal from the ethylene receptor complex at the endoplasmic reticulum (ER) membrane to transcription factors in the nucleus is unknown. To close this gap in our understanding of the ethylene signaling pathway, the challenge has been to identify the target of the CONSTITUTIVE TRIPLE RESPONSE1 (CTR1) Raf-like protein kinase, as well as the molecular events surrounding ETHYLENE-INSENSITIVE2 (EIN2), an ER membrane-localized Nramp homolog that positively regulates ethylene responses. Here we demonstrate that CTR1 interacts with and directly phosphorylates the cytosolic C-terminal domain of EIN2. Mutations that block the EIN2 phosphorylation sites result in constitutive nuclear localization of the EIN2 C terminus, concomitant with constitutive activation of ethylene responses in Arabidopsis. Our results suggest that phosphorylation of EIN2 by CTR1 prevents EIN2 from signaling in the absence of ethylene, whereas inhibition of CTR1 upon ethylene perception is a signal for cleavage and nuclear localization of the EIN2 C terminus, allowing the ethylene signal to reach the downstream transcription factors. These findings significantly advance our understanding of the mechanisms underlying ethylene signal transduction. PMID:23132950

Cell signaling and transcription factor genes expressed during whole body regeneration in a colonial chordate.

PubMed

Rinkevich, Yuval; Rinkevich, Baruch; Reshef, Ram

2008-10-12

The restoration of adults from fragments of blood vessels in botryllid ascidians (termed whole body regeneration [WBR]) represents an inimitable event in the chordates, which is poorly understood on the mechanistic level. To elucidate mechanisms underlying this phenomenon, a subtracted EST library for early WBR stages was previously assembled, revealing 76 putative genes belonging to major signaling pathways, including Notch/Delta, JAK/STAT, protein kinases, nuclear receptors, Ras oncogene family members, G-Protein coupled receptor (GPCR) and transforming growth factor beta (TGF-beta) signaling. RT-PCR on selected transcripts documented specific up-regulation in only regenerating fragments, pointing to a broad activation of these signaling pathways at onset of WBR. The followed-up expression pattern of seven representative transcripts from JAK/STAT signaling (Bl-STAT), the Ras oncogene family (Bl-Rap1A, Bl-Rab-33), the protein kinase family (Bl-Mnk), Bl-Cnot, Bl-Slit and Bl-Bax inhibitor, revealed systemic and site specific activations during WBR in a sub-population of circulatory cells. WBR in the non-vertebrate chordate Botrylloides leachi is a multifaceted phenomenon, presided by a complex array of cell signaling and transcription factors. Above results, provide a first insight into the whole genome molecular machinery of this unique regeneration process, and reveal the broad participation of cell signaling and transcription factors in the process. While regeneration involves the participation of specific cell populations, WBR signals are systemically expressed at the organism level.

Using gravity as a proxy for stress accumulation in complex fault systems

NASA Astrophysics Data System (ADS)

Hayes, Tyler Joseph

The gravity signal contains information regarding changes in density at all depths and can be used as a proxy for the strain accumulation in fault networks. A general method for calculating the total, dilatational, and free-air gravity for fault systems with arbitrary geometry, slip motion, and number of fault segments is presented. The technique uses a Green's function approach for a fault buried within an elastic half-space with an underlying driver plate forcing the system. A stress-evolution time-dependent earthquake fault model was used to create simulated slip histories over the San Andreas Fault network in California. Using a sum of the gravity signals from each fault segment in the model, via coseismic gravity Green's functions, a time-dependent gravity model was created. The steady-state gravity from the long term plate motion generates a signal over five years with magnitudes of +/- ˜2 muGal; the current limit of portable instrument observations. Moderate to large events generate signal magnitudes in the range of ˜10 muGal to ˜80 muGal, well within the range of ground based observations. The complex fault network geometry of California significantly affects the spatial extent of the gravity signal from the three events studied. Statistical analysis of 55 000 years of simulated slip histories were used to investigate the use of the dilatational gravity signal as a proxy for precursory stress and strain changes. Results indicate that the precursory dilatational gravity signal is dependent upon the fault orientation with respect the tectonic loading plate velocity. This effect is interpreted as a consequence of preferential amplification of the shear stress or reduction of the normal stress, depending on the steady-state regime investigated. Finally, solutions for the corresponding gravity gradients of the coseismic dilatational gravity signals are developed for a vertical strike-slip fault. Gravity gradient solutions exhibit similar spatial distributions as those calculated for Coulomb stress changes, reflecting their physical relationship to the stress changes. The magnitude of the signals, on the order of 1 x 10-4 E, are beyond the resolution of typical exploration instruments at the present time. Keywords. numerical solutions; seismic cycle; gravity; gravity gradients; time variable gravity; earthquake interaction; forecasting; and prediction

Bayesian reconstruction of gravitational wave bursts using chirplets

NASA Astrophysics Data System (ADS)

Millhouse, Margaret; Cornish, Neil J.; Littenberg, Tyson

2018-05-01

The LIGO-Virgo Collaboration uses a variety of techniques to detect and characterize gravitational waves. One approach is to use templates—models for the signals derived from Einstein's equations. Another approach is to extract the signals directly from the coherent response of the detectors in the LIGO-Virgo network. Both approaches played an important role in the first gravitational wave detections. Here we extend the BayesWave analysis algorithm, which reconstructs gravitational wave signals using a collection of continuous wavelets, to use a generalized wavelet family, known as chirplets, that have time-evolving frequency content. Since generic gravitational wave signals have frequency content that evolves in time, a collection of chirplets provides a more compact representation of the signal, resulting in more accurate waveform reconstructions, especially for low signal-to-noise events, and events that occupy a large time-frequency volume.

Detecting paralinguistic events in audio stream using context in features and probabilistic decisions☆

PubMed Central

Gupta, Rahul; Audhkhasi, Kartik; Lee, Sungbok; Narayanan, Shrikanth

2017-01-01

Non-verbal communication involves encoding, transmission and decoding of non-lexical cues and is realized using vocal (e.g. prosody) or visual (e.g. gaze, body language) channels during conversation. These cues perform the function of maintaining conversational flow, expressing emotions, and marking personality and interpersonal attitude. In particular, non-verbal cues in speech such as paralanguage and non-verbal vocal events (e.g. laughters, sighs, cries) are used to nuance meaning and convey emotions, mood and attitude. For instance, laughters are associated with affective expressions while fillers (e.g. um, ah, um) are used to hold floor during a conversation. In this paper we present an automatic non-verbal vocal events detection system focusing on the detect of laughter and fillers. We extend our system presented during Interspeech 2013 Social Signals Sub-challenge (that was the winning entry in the challenge) for frame-wise event detection and test several schemes for incorporating local context during detection. Specifically, we incorporate context at two separate levels in our system: (i) the raw frame-wise features and, (ii) the output decisions. Furthermore, our system processes the output probabilities based on a few heuristic rules in order to reduce erroneous frame-based predictions. Our overall system achieves an Area Under the Receiver Operating Characteristics curve of 95.3% for detecting laughters and 90.4% for fillers on the test set drawn from the data specifications of the Interspeech 2013 Social Signals Sub-challenge. We perform further analysis to understand the interrelation between the features and obtained results. Specifically, we conduct a feature sensitivity analysis and correlate it with each feature's stand alone performance. The observations suggest that the trained system is more sensitive to a feature carrying higher discriminability with implications towards a better system design. PMID:28713197

Real alerts and artifact classification in archived multi-signal vital sign monitoring data: implications for mining big data.

PubMed

Hravnak, Marilyn; Chen, Lujie; Dubrawski, Artur; Bose, Eliezer; Clermont, Gilles; Pinsky, Michael R

2016-12-01

Huge hospital information system databases can be mined for knowledge discovery and decision support, but artifact in stored non-invasive vital sign (VS) high-frequency data streams limits its use. We used machine-learning (ML) algorithms trained on expert-labeled VS data streams to automatically classify VS alerts as real or artifact, thereby "cleaning" such data for future modeling. 634 admissions to a step-down unit had recorded continuous noninvasive VS monitoring data [heart rate (HR), respiratory rate (RR), peripheral arterial oxygen saturation (SpO 2 ) at 1/20 Hz, and noninvasive oscillometric blood pressure (BP)]. Time data were across stability thresholds defined VS event epochs. Data were divided Block 1 as the ML training/cross-validation set and Block 2 the test set. Expert clinicians annotated Block 1 events as perceived real or artifact. After feature extraction, ML algorithms were trained to create and validate models automatically classifying events as real or artifact. The models were then tested on Block 2. Block 1 yielded 812 VS events, with 214 (26 %) judged by experts as artifact (RR 43 %, SpO 2 40 %, BP 15 %, HR 2 %). ML algorithms applied to the Block 1 training/cross-validation set (tenfold cross-validation) gave area under the curve (AUC) scores of 0.97 RR, 0.91 BP and 0.76 SpO 2 . Performance when applied to Block 2 test data was AUC 0.94 RR, 0.84 BP and 0.72 SpO 2 . ML-defined algorithms applied to archived multi-signal continuous VS monitoring data allowed accurate automated classification of VS alerts as real or artifact, and could support data mining for future model building.

Real Alerts and Artifact Classification in Archived Multi-signal Vital Sign Monitoring Data—Implications for Mining Big Data — Implications for Mining Big Data

PubMed Central

Hravnak, Marilyn; Chen, Lujie; Dubrawski, Artur; Bose, Eliezer; Clermont, Gilles; Pinsky, Michael R.

2015-01-01

PURPOSE Huge hospital information system databases can be mined for knowledge discovery and decision support, but artifact in stored non-invasive vital sign (VS) high-frequency data streams limits its use. We used machine-learning (ML) algorithms trained on expert-labeled VS data streams to automatically classify VS alerts as real or artifact, thereby “cleaning” such data for future modeling. METHODS 634 admissions to a step-down unit had recorded continuous noninvasive VS monitoring data (heart rate [HR], respiratory rate [RR], peripheral arterial oxygen saturation [SpO2] at 1/20Hz., and noninvasive oscillometric blood pressure [BP]) Time data were across stability thresholds defined VS event epochs. Data were divided Block 1 as the ML training/cross-validation set and Block 2 the test set. Expert clinicians annotated Block 1 events as perceived real or artifact. After feature extraction, ML algorithms were trained to create and validate models automatically classifying events as real or artifact. The models were then tested on Block 2. RESULTS Block 1 yielded 812 VS events, with 214 (26%) judged by experts as artifact (RR 43%, SpO2 40%, BP 15%, HR 2%). ML algorithms applied to the Block 1 training/cross-validation set (10-fold cross-validation) gave area under the curve (AUC) scores of 0.97 RR, 0.91 BP and 0.76 SpO2. Performance when applied to Block 2 test data was AUC 0.94 RR, 0.84 BP and 0.72 SpO2). CONCLUSIONS ML-defined algorithms applied to archived multi-signal continuous VS monitoring data allowed accurate automated classification of VS alerts as real or artifact, and could support data mining for future model building. PMID:26438655

Biased signaling of the proton-sensing receptor OGR1 by benzodiazepines.

PubMed

Pera, Tonio; Deshpande, Deepak A; Ippolito, Michael; Wang, Bin; Gavrila, Adelina; Michael, James V; Nayak, Ajay P; Tompkins, Eric; Farrell, Eleni; Kroeze, Wesley K; Roth, Bryan L; Panettieri, Reynold A; Benovic, Jeffrey L; An, Steven S; Dulin, Nickolai O; Penn, Raymond B

2018-02-01

GPCRs have diverse signaling capabilities, based on their ability to assume various conformations. Moreover, it is now appreciated that certain ligands can promote distinct receptor conformations and thereby bias signaling toward a specific pathway to differentially affect cell function. The recently deorphanized G protein-coupled receptor OGR1 [ovarian cancer G protein-coupled receptor 1 ( GPR68)] exhibits diverse signaling events when stimulated by reductions in extracellular pH. We recently demonstrated airway smooth muscle cells transduce multiple signaling events, reflecting a diverse capacity to couple to multiple G proteins. Moreover, we recently discovered that the benzodiazepine lorazepam, more commonly recognized as an agonist of the γ-aminobutyric acid A (GABA A ) receptor, can function as an allosteric modulator of OGR1 and, similarly, can promote multiple signaling events. In this study, we demonstrated that different benzodiazepines exhibit a range of biases for OGR1, with sulazepam selectively activating the canonical Gs of the G protein signaling pathway, in heterologous expression systems, as well as in several primary cell types. These findings highlight the potential power of biased ligand pharmacology for manipulating receptor signaling qualitatively, to preferentially activate pathways that are therapeutically beneficial.-Pera, T., Deshpande, D. A., Ippolito, M., Wang, B., Gavrila, A., Michael, J. V., Nayak, A. P., Tompkins, E., Farrell, E., Kroeze, W. K., Roth, B. L., Panettieri, R. A. Jr Benovic, J. L., An, S. S., Dulin, N. O., Penn, R. B. Biased signaling of the proton-sensing receptor OGR1 by benzodiazepines.

Tensile stress stimulates microtubule outgrowth in living cells

NASA Technical Reports Server (NTRS)

Kaverina, Irina; Krylyshkina, Olga; Beningo, Karen; Anderson, Kurt; Wang, Yu-Li; Small, J. Victor

2002-01-01

Cell motility is driven by the sum of asymmetric traction forces exerted on the substrate through adhesion foci that interface with the actin cytoskeleton. Establishment of this asymmetry involves microtubules, which exert a destabilising effect on adhesion foci via targeting events. Here, we demonstrate the existence of a mechano-sensing mechanism that signals microtubule polymerisation and guidance of the microtubules towards adhesion sites under increased stress. Stress was applied either by manipulating the body of cells moving on glass with a microneedle or by stretching a flexible substrate that cells were migrating on. We propose a model for this mechano-sensing phenomenon whereby microtubule polymerisation is stimulated and guided through the interaction of a microtubule tip complex with actin filaments under tension.

Transfer of fuel assemblies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vuckovich, M.; Burkett, J. P.; Sallustio, J.

1984-12-11

Fuel assemblies of a nuclear reactor are transferred during fueling or refueling or the like by a crane. The work-engaging fixture of the crane picks up an assembly, removes it from this slot, transfers it to the deposit site and deposits it in its slot at the deposit site. The control for the crane includes a strain gauge connected to the crane line which raises and lowers the load. The strain gauge senses the load on the crane. The signal from the strain gauge is compared with setpoints; a high-level setpoint, a low-level setpoint and a slack-line setpoint. If themore » strain gauge signal exceeds the high-level setpoint, the line drive is disabled. This event may occur during raising of a fuel assembly which encounters resistance. The high-level setpoint may be overridden under proper precautions. The line drive is also disabled if the strain gauge signal is less than the low-level setpoint. This event occurs when a fuel assembly being deposited contacts the bottom of its slot or an obstruction in, or at the entry to the slot. To preclude lateral movement and possible damage to a fuel assembly suspended from the crane line, the traverse drive of the crane is disabled once the strain-gauge exceets the lov-level setpoint. The traverse drive can only be enabled after the strain-gauge signal is less than the slack-line set-point. This occurs when the lines has been set in slack-line setting. When the line is tensioned after slack-li ne setting, the traverse drive remains enabled only if the line has been disconnected from the fuel assembly.« less

Calcium Signalling through Ligand-Gated Ion Channels such as P2X1 Receptors in the Platelet and other Non-Excitable Cells.

PubMed

Mahaut-Smith, Martyn P; Taylor, Kirk A; Evans, Richard J

2016-01-01

Ligand-gated ion channels on the cell surface are directly activated by the binding of an agonist to their extracellular domain and often referred to as ionotropic receptors. P2X receptors are ligand-gated non-selective cation channels with significant permeability to Ca(2+) whose principal physiological agonist is ATP. This chapter focuses on the mechanisms by which P2X1 receptors, a ubiquitously expressed member of the family of ATP-gated channels, can contribute to cellular responses in non-excitable cells. Much of the detailed information on the contribution of P2X1 to Ca(2+) signalling and downstream functional events has been derived from the platelet. The underlying primary P2X1-generated signalling event in non-excitable cells is principally due to Ca(2+) influx, although Na(+) entry will also occur along with membrane depolarization. P2X1 receptor stimulation can lead to additional Ca(2+) mobilization via a range of routes such as amplification of G-protein-coupled receptor-dependent Ca(2+) responses. This chapter also considers the mechanism by which cells generate extracellular ATP for autocrine or paracrine activation of P2X1 receptors. For example cytosolic ATP efflux can result from opening of pannexin anion-permeable channels or following damage to the cell membrane. Alternatively, ATP stored in specialised secretory vesicles can undergo quantal release via the process of exocytosis. Examples of physiological or pathophysiological roles of P2X1-dependent signalling in non-excitable cells are also discussed, such as thrombosis and immune responses.

Auxin acts as a local morphogenetic trigger to specify lateral root founder cells

PubMed Central

Dubrovsky, Joseph G.; Sauer, Michael; Napsucialy-Mendivil, Selene; Ivanchenko, Maria G.; Friml, Jiří; Shishkova, Svetlana; Celenza, John; Benková, Eva

2008-01-01

Plants exhibit an exceptional adaptability to different environmental conditions. To a large extent, this adaptability depends on their ability to initiate and form new organs throughout their entire postembryonic life. Plant shoot and root systems unceasingly branch and form axillary shoots or lateral roots, respectively. The first event in the formation of a new organ is specification of founder cells. Several plant hormones, prominent among them auxin, have been implicated in the acquisition of founder cell identity by differentiated cells, but the mechanisms underlying this process are largely elusive. Here, we show that auxin and its local accumulation in root pericycle cells is a necessary and sufficient signal to respecify these cells into lateral root founder cells. Analysis of the alf4–1 mutant suggests that specification of founder cells and the subsequent activation of cell division leading to primordium formation represent two genetically separable events. Time-lapse experiments show that the activation of an auxin response is the earliest detectable event in founder cell specification. Accordingly, local activation of auxin response correlates absolutely with the acquisition of founder cell identity and precedes the actual formation of a lateral root primordium through patterned cell division. Local production and subsequent accumulation of auxin in single pericycle cells induced by Cre-Lox-based activation of auxin synthesis converts them into founder cells. Thus, auxin is the local instructive signal that is sufficient for acquisition of founder cell identity and can be considered a morphogenetic trigger in postembryonic plant organogenesis. PMID:18559858

Characteristics of acoustic emissions from shearing of granular media

NASA Astrophysics Data System (ADS)

Michlmayr, Gernot; Cohen, Denis; Or, Dani

2010-05-01

Deformation and abrupt formation of small failure cracks on hillslopes often precede sudden release of shallow landslides. The associated frictional sliding, breakage of cementing agents and rupture of embedded biological fibers or liquid bonds between grain contacts are associated with measurable acoustic emissions (AE). The aim of this study was to characterize small scale shear induced failure events (as models of precursors prior to a landslide) by capturing elastic body waves emitted from such events. We conducted a series of experiments with a specially-designed shear frame to measure and characterize high frequency (kHz range) acoustic emissions under different conditions using piezoelectric sensors. Tests were performed at different shear rates ranging from 0.01mm/sec to 2mm/sec with different dry and wet granular materials. In addition to acoustic emissions the setup allows to measure forces and deformations in both horizontal and vertical directions. Results provide means to define characteristic AE signature for different failure events. We observed an increase in AE activity during dilation of granular samples. In wet material AE signals were attributed to the snap-off of liquid bridges between single gains. Acoustic emissions clearly provide an experimental tool for exploring micro-mechanical processes in dry and wet material. Moreover, high sampling rates found in most AE systems coupled with waveguides to overcome signal attenuation offer a promise for field applications as an early warning method for observing the progressive development of slip planes prior to the onset of a landslide.

Gdf5 progenitors give rise to fibrocartilage cells that mineralize via hedgehog signaling to form the zonal enthesis.

PubMed

Dyment, Nathaniel A; Breidenbach, Andrew P; Schwartz, Andrea G; Russell, Ryan P; Aschbacher-Smith, Lindsey; Liu, Han; Hagiwara, Yusuke; Jiang, Rulang; Thomopoulos, Stavros; Butler, David L; Rowe, David W

2015-09-01

The sequence of events that leads to the formation of a functionally graded enthesis is not clearly defined. The current study demonstrates that clonal expansion of Gdf5 progenitors contributes to linear growth of the enthesis. Prior to mineralization, Col1+ cells in the enthesis appose Col2+ cells of the underlying primary cartilage. At the onset of enthesis mineralization, cells at the base of the enthesis express alkaline phosphatase, Indian hedgehog, and ColX as they mineralize. The mineralization front then extends towards the tendon midsubstance as cells above the front become encapsulated in mineralized fibrocartilage over time. The hedgehog (Hh) pathway regulates this process, as Hh-responsive Gli1+ cells within the developing enthesis mature from unmineralized to mineralized fibrochondrocytes in response to activated signaling. Hh signaling is required for mineralization, as tissue-specific deletion of its obligate transducer Smoothened in the developing tendon and enthesis cells leads to significant reductions in the apposition of mineralized fibrocartilage. Together, these findings provide a spatiotemporal map of events - from expansion of the embryonic progenitor pool to synthesis of the collagen template and finally mineralization of this template - that leads to the formation of the mature zonal enthesis. These results can inform future tendon-to-bone repair strategies to create a mechanically functional enthesis in which tendon collagen fibers are anchored to bone through mineralized fibrocartilage. Copyright © 2015 Elsevier Inc. All rights reserved.

Search for $$\\mathrm{t\\overline{t}}$$H production in the $$H\\to\\mathrm{b\\overline{b}}$$ decay channel with leptonic $$\\mathrm{t\\overline{t}}$$ decays in proton-proton collisions at $$\\sqrt{s}=$$ 13 TeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sirunyan, Albert M; et al.

A search is presented for the associated production of a standard model Higgs boson with a top quark-antiquark pair (more » $$\\mathrm{t\\overline{t}}$$H), in which the Higgs boson decays into a b quark-antiquark pair, in proton-proton collisions at a centre-of-mass energy $$\\sqrt{s}=$$ 13 TeV. The data correspond to an integrated luminosity of 35.9 fb$${-1}$$ recorded with the CMS detector at the CERN LHC. Candidate $$\\mathrm{t\\overline{t}}$$H events are selected that contain either one or two electrons or muons from the \\ttbar decays and are categorised according to the number of jets. Multivariate techniques are employed to further classify the events and eventually discriminate between signal and background. The results are characterised by an observed $$\\mathrm{t\\overline{t}}$$H signal strength relative to the standard model cross section, $$\\mu = \\sigma/\\sigma_{\\mathrm{SM}}$$, under the assumption of a Higgs boson mass of 125 GeV. A combined fit of multivariate discriminant distributions in all categories results in an observed (expected) upper limit on $$\\mu$$ of 1.5 (0.9) at 95% confidence level, and a best fit value of 0.72$$\\pm$$0.24 (stat) $$\\pm$$0.38 (syst), corresponding to an observed (expected) signal significance of 1.6 (2.2) standard deviations above the background-only hypothesis.« less

Cortical GABAergic excitation contributes to epileptic activities around human glioma

PubMed Central

Pallud, Johan; Varlet, Pascale; Cresto, Noemie; Baulac, Michel; Duyckaerts, Charles; Kourdougli, Nazim; Chazal, Geneviève; Devaux, Bertrand; Rivera, Claudio; Miles, Richard; Capelle, Laurent; Huberfeld, Gilles

2015-01-01

Rationale Diffuse brain gliomas induce seizures in a majority of patients. As in most epileptic disorders, excitatory glutamatergic mechanisms are involved in the generation of epileptic activities in the neocortex surrounding gliomas. However, chloride homeostasis is known to be perturbed in glial tumor cells. Thus the contribution of GABAergic mechanisms which depend on intracellular chloride and which are defective or pro-epileptic in other structural epilepsies merits closer study. Objective We studied in neocortical slices from the peritumoral security margin resected around human brain gliomas, the occurrence, networks, cells and signaling basis of epileptic activities. Results Postoperative glioma tissue from 69% of patients spontaneously generated interictal-like discharges. These events were synchronized, with a high frequency oscillation signature, in superficial layers of neocortex around glioma areas with tumor infiltration. Interictal-like events depended on both glutamatergic transmission and on depolarizing GABAergic signaling. About 65% of pyramidal cells were depolarized by GABA released by interneurons. This effect was related to perturbations in Chloride homeostasis, due to changes in expression of chloride co-transporters: KCC2 was reduced and expression of NKCC1 increased. Ictal-like activities were initiated by convulsant stimuli exclusively in these epileptogenic areas. Conclusions Epileptic activities are sustained by excitatory effects of GABA in the peritumoral human neocortex, as in temporal lobe epilepsies. Glutamate and GABA signaling are involved in oncogenesis and chloride homeostasis is perturbed. These same factors, induce an imbalance between synaptic excitatory and inhibition underly epileptic discharges in tumor patients. PMID:25009229

Solar observations with a low frequency radio telescope

NASA Astrophysics Data System (ADS)

Myserlis, I.; Seiradakis, J.; Dogramatzidis, M.

2012-01-01

We have set up a low frequency radio monitoring station for solar bursts at the Observatory of the Aristotle University in Thessaloniki. The station consists of a dual dipole phased array, a radio receiver and a dedicated computer with the necessary software installed. The constructed radio receiver is based on NASA's Radio Jove project. It operates continuously, since July 2010, at 20.1 MHz (close to the long-wavelength ionospheric cut-off of the radio window) with a narrow bandwidth (~5 kHz). The system is properly calibrated, so that the recorded data are expressed in antenna temperature. Despite the high interference level of an urban region like Thessaloniki (strong broadcasting shortwave radio stations, periodic experimental signals, CBs, etc), we have detected several low frequency solar radio bursts and correlated them with solar flares, X-ray events and other low frequency solar observations. The received signal is monitored in ordinary ASCII format and as audio signal, in order to investigate and exclude man-made radio interference. In order to exclude narrow band interference and calculate the spectral indices of the observed events, a second monitoring station, working at 36 MHz, is under construction at the village of Nikiforos near the town of Drama, about 130 km away of Thessaloniki. Finally, we plan to construct a third monitoring station at 58 MHz, in Thessaloniki. This frequency was revealed to be relatively free of interference, after a thorough investigation of the region.

TP53-dependent autophagy links the ATR-CHEK1 axis activation to proinflammatory VEGFA production in human bronchial epithelial cells exposed to fine particulate matter (PM2.5).

PubMed

Xu, Xiuduan; Wang, Hongli; Liu, Shasha; Xing, Chen; Liu, Yang; Aodengqimuge; Zhou, Wei; Yuan, Xiaoyan; Ma, Yongfu; Hu, Meiru; Hu, Yongliang; Zou, Shuxian; Gu, Ye; Peng, Shuangqing; Yuan, Shengtao; Li, Weiping; Ma, Yuanfang; Song, Lun

2016-10-02

ABSTARCT Epidemiological and clinical studies have increasingly shown that fine particulate matter (PM2.5) is associated with a number of pathological respiratory diseases, such as bronchitis, asthma, and chronic obstructive pulmonary disease, which share the common feature of airway inflammation induced by particle exposure. Thus, understanding how PM2.5 triggers inflammatory responses in the respiratory system is crucial for the study of PM2.5 toxicity. In the current study, we found that exposing human bronchial epithelial cells (immortalized Beas-2B cells and primary cells) to PM2.5 collected in the winter in Wuhan, a city in southern China, induced a significant upregulation of VEGFA (vascular endothelial growth factor A) production, a signaling event that typically functions to control chronic airway inflammation and vascular remodeling. Further investigations showed that macroautophagy/autophagy was induced upon PM2.5 exposure and then mediated VEGFA upregulation by activating the SRC (SRC proto-oncogene, non-receptor tyrosine kinase)-STAT3 (signal transducer and activator of transcription 3) pathway in bronchial epithelial cells. By exploring the upstream signaling events responsible for autophagy induction, we revealed a requirement for TP53 (tumor protein p53) activation and the expression of its downstream target DRAM1 (DNA damage regulated autophagy modulator 1) for the induction of autophagy. These results thus extend the role of TP53-DRAM1-dependent autophagy beyond cell fate determination under genotoxic stress and to the control of proinflammatory cytokine production. Moreover, PM2.5 exposure strongly induced the activation of the ATR (ATR serine/threonine kinase)-CHEK1/CHK1 (checkpoint kinase 1) axis, which subsequently triggered TP53-dependent autophagy and VEGFA production in Beas-2B cells. Therefore, these findings suggest a novel link between processes regulating genomic integrity and airway inflammation via autophagy induction in bronchial epithelial cells under PM2.5 exposure.

An integrated pathway system modeling of Saccharomyces cerevisiae HOG pathway: a Petri net based approach.

PubMed

Tomar, Namrata; Choudhury, Olivia; Chakrabarty, Ankush; De, Rajat K

2013-02-01

Biochemical networks comprise many diverse components and interactions between them. It has intracellular signaling, metabolic and gene regulatory pathways which are highly integrated and whose responses are elicited by extracellular actions. Previous modeling techniques mostly consider each pathway independently without focusing on the interrelation of these which actually functions as a single system. In this paper, we propose an approach of modeling an integrated pathway using an event-driven modeling tool, i.e., Petri nets (PNs). PNs have the ability to simulate the dynamics of the system with high levels of accuracy. The integrated set of signaling, regulatory and metabolic reactions involved in Saccharomyces cerevisiae's HOG pathway has been collected from the literature. The kinetic parameter values have been used for transition firings. The dynamics of the system has been simulated and the concentrations of major biological species over time have been observed. The phenotypic characteristics of the integrated system have been investigated under two conditions, viz., under the absence and presence of osmotic pressure. The results have been validated favorably with the existing experimental results. We have also compared our study with the study of idFBA (Lee et al., PLoS Comput Biol 4:e1000-e1086, 2008) and pointed out the differences between both studies. We have simulated and monitored concentrations of multiple biological entities over time and also incorporated feedback inhibition by Ptp2 which has not been included in the idFBA study. We have concluded that our study is the first to the best of our knowledge to model signaling, metabolic and regulatory events in an integrated form through PN model framework. This study is useful in computational simulation of system dynamics for integrated pathways as there are growing evidences that the malfunctioning of the interplay among these pathways is associated with disease.

Signal analysis and radioholographic methods for airborne radio occultations

NASA Astrophysics Data System (ADS)

Wang, Kuo-Nung

Global Positioning System (GPS) radio occultation (RO) is an atmospheric sounding technique utilizing the change in propagation direction and delay of the GPS signal to measure refractivity, which provides information on temperature and humidity. The GPS-RO technique is now operational on several Low Earth Orbiting (LEO) satellite missions. Nevertheless, when observing localized transient events, such as tropical storms, current LEO satellite systems cannot provide sufficiently high temporal and spatial resolution soundings. An airborne RO (ARO) system has therefore been developed for localized GPS-RO campaigns. The open-loop (OL) tracking in post-processing is used to cross-correlates the received Global Navigation Satellite System (GNSS) signal with an internally generated local carrier signal predicted from a Doppler model and extract the atmospheric refractivity information. OL tracking also allows robust processing of rising GPS signals using backward tracking, which will double the observed occultation event numbers. RO signals in the lower troposphere are adversely affected by rapid phase accelerations and severe signal power fading, however. The negative bias caused by low signal-to-noise ratio (SNR) and multipath ray propagation limits the depth of tracking in the atmosphere. Therefore, we developed a model relating the SNR to the variance in the residual phase of the observed signal produced from OL tracking, and its applicability to airborne data is demonstrated. We then apply this model to set a threshold on refractivity retrieval, based upon the cumulative unwrapping error bias, to determine the altitude limit for reliable signal tracking. To enhance the SNR and decrease the unwrapping error rate, the CIRA-Q climatological model and signal residual phase pre-filtering are utilized to process the ARO residual phase. This more accurately modeled phase and less noisy received signal are shown to greatly reduce the bias caused by unwrapping error at lower altitude. On the other hand, to process the superimposed signal in the lower troposphere with its highly variable moisture distribution, Radio-Holographic (RH) methods such as Phase Matching (PM) have been adapted for ARO platforms to untangle the bending angle of each signal path. Under the assumption of spherically symmetric atmosphere, ARO PM can identify different subsignals using the Method of the Stationary Phase (MSP) and determine the arrival angle for each impact parameter. As a result, each subsignal can be distinguished and its corresponding bending angle can be retrieved without producing a negative bias. The refractivity retrieval results using ARO PM are compared to those using the traditional Geometrical Optics (GO) method. The improvements are shown and discussed in the dissertation. We applied these new methods to the received ARO data collected by the GNSS instrument system for multistatic and occultation sensing (GISMOS) in the 2010 PREDepression Investigation of Cloud systems (PREDICT) campaign. A data set of 5 research flights with 57 occultation events during the formation stage of the Hurricane Karl are processed and analyzed. In this research, the refractivity fractional difference with ERA-I model can be maintained at an average 2% above a height of 2km with a climatological model and ARO PM. Compared to the traditional geometrical optics (GO) method without climatological method assistance, the new ARO processing can effectively decrease the refractivity negative bias and significantly improve the retrieval depth of ARO.

Characterizing dark matter at the LHC in Drell-Yan events

NASA Astrophysics Data System (ADS)

Capdevilla, Rodolfo M.; Delgado, Antonio; Martin, Adam; Raj, Nirmal

2018-02-01

Spectral features in LHC dileptonic events may signal radiative corrections coming from new degrees of freedom, notably dark matter and mediators. Using simplified models, and under a set of simplifying assumptions, we show how these features can reveal the fundamental properties of the dark sector, such as self-conjugation, spin and mass of dark matter, and the quantum numbers of the mediator. Distributions of both the invariant mass mℓℓ and the Collins-Soper scattering angle cos θCS are studied to pinpoint these properties. We derive constraints on the models from LHC measurements of mℓℓ and cos θCS, which are competitive with direct detection and jets+MET searches. We find that in certain scenarios the cos θCS spectrum provides the strongest bounds, underlining the importance of scattering angle measurements for nonresonant new physics.

Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury*

PubMed Central

van Niekerk, Erna A.; Tuszynski, Mark H.; Lu, Paul; Dulin, Jennifer N.

2016-01-01

Following axotomy, a complex temporal and spatial coordination of molecular events enables regeneration of the peripheral nerve. In contrast, multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration in the central nervous system. In this review, we examine the current understanding of differences in protein expression and post-translational modifications, activation of signaling networks, and environmental cues that may underlie the divergent regenerative capacity of central and peripheral axons. We also highlight key experimental strategies to enhance axonal regeneration via modulation of intraneuronal signaling networks and the extracellular milieu. Finally, we explore potential applications of proteomics to fill gaps in the current understanding of molecular mechanisms underlying regeneration, and to provide insight into the development of more effective approaches to promote axonal regeneration following injury to the nervous system. PMID:26695766

Therapeutic potential of agmatine for CNS disorders.

PubMed

Neis, Vivian B; Rosa, Priscila B; Olescowicz, Gislaine; Rodrigues, Ana Lúcia S

2017-09-01

Agmatine is a neuromodulator that regulates multiple neurotransmitters and signaling pathways. Several studies have focused on elucidating the mechanisms underlying the neuroprotective effects of this molecule, which seems to be mediated by a reduction in oxidative damage, neuroinflammation, and proapoptotic signaling. Since these events are implicated in acute and chronic excitotoxicity-related disorders (ischemia, epilepsy, traumatic brain injury, spinal cord injury, neurodegenerative, and psychiatric disorders) as well as in nociception, agmatine has been proposed as a therapeutic strategy for the treatment of central nervous system (CNS) disorders. Agmatine also stimulates the expression of trophic factors and adult neurogenesis, contributing to its ability to induce endogenous repair mechanisms. Therefore, considering its wide range of biological effects, this review summarizes the current knowledge about its protective and regenerative properties in the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

The sequentially discounting autoregressive (SDAR) method for on-line automatic seismic event detecting on long term observation

NASA Astrophysics Data System (ADS)

Wang, L.; Toshioka, T.; Nakajima, T.; Narita, A.; Xue, Z.

2017-12-01

In recent years, more and more Carbon Capture and Storage (CCS) studies focus on seismicity monitoring. For the safety management of geological CO2 storage at Tomakomai, Hokkaido, Japan, an Advanced Traffic Light System (ATLS) combined different seismic messages (magnitudes, phases, distributions et al.) is proposed for injection controlling. The primary task for ATLS is the seismic events detection in a long-term sustained time series record. Considering the time-varying characteristics of Signal to Noise Ratio (SNR) of a long-term record and the uneven energy distributions of seismic event waveforms will increase the difficulty in automatic seismic detecting, in this work, an improved probability autoregressive (AR) method for automatic seismic event detecting is applied. This algorithm, called sequentially discounting AR learning (SDAR), can identify the effective seismic event in the time series through the Change Point detection (CPD) of the seismic record. In this method, an anomaly signal (seismic event) can be designed as a change point on the time series (seismic record). The statistical model of the signal in the neighborhood of event point will change, because of the seismic event occurrence. This means the SDAR aims to find the statistical irregularities of the record thought CPD. There are 3 advantages of SDAR. 1. Anti-noise ability. The SDAR does not use waveform messages (such as amplitude, energy, polarization) for signal detecting. Therefore, it is an appropriate technique for low SNR data. 2. Real-time estimation. When new data appears in the record, the probability distribution models can be automatic updated by SDAR for on-line processing. 3. Discounting property. the SDAR introduces a discounting parameter to decrease the influence of present statistic value on future data. It makes SDAR as a robust algorithm for non-stationary signal processing. Within these 3 advantages, the SDAR method can handle the non-stationary time-varying long-term series and achieve real-time monitoring. Finally, we employ the SDAR on a synthetic model and Tomakomai Ocean Bottom Cable (OBC) baseline data to prove the feasibility and advantage of our method.

Sleep Apnea Detection Based on Thoracic and Abdominal Movement Signals of Wearable Piezo-Electric Bands.

PubMed

Lin, Yin-Yan; Wu, Hau-Tieng; Hsu, Chi-An; Huang, Po-Chiun; Huang, Yuan-Hao; Lo, Yu-Lun

2016-12-07

Physiologically, the thoracic (THO) and abdominal (ABD) movement signals, captured using wearable piezo-electric bands, provide information about various types of apnea, including central sleep apnea (CSA) and obstructive sleep apnea (OSA). However, the use of piezo-electric wearables in detecting sleep apnea events has been seldom explored in the literature. This study explored the possibility of identifying sleep apnea events, including OSA and CSA, by solely analyzing one or both the THO and ABD signals. An adaptive non-harmonic model was introduced to model the THO and ABD signals, which allows us to design features for sleep apnea events. To confirm the suitability of the extracted features, a support vector machine was applied to classify three categories - normal and hypopnea, OSA, and CSA. According to a database of 34 subjects, the overall classification accuracies were on average 75.9%±11.7% and 73.8%±4.4%, respectively, based on the cross validation. When the features determined from the THO and ABD signals were combined, the overall classification accuracy became 81.8%±9.4%. These features were applied for designing a state machine for online apnea event detection. Two event-byevent accuracy indices, S and I, were proposed for evaluating the performance of the state machine. For the same database, the S index was 84.01%±9.06%, and the I index was 77.21%±19.01%. The results indicate the considerable potential of applying the proposed algorithm to clinical examinations for both screening and homecare purposes.

Long recovery VLF perturbations associated with lightning discharges

NASA Astrophysics Data System (ADS)

Salut, M. M.; Abdullah, M.; Graf, K. L.; Cohen, M. B.; Cotts, B. R. T.; Kumar, Sushil

2012-08-01

Long D-region ionospheric recovery perturbations are a recently discovered and poorly understood subcategory of early VLF events, distinguished by exceptionally long ionospheric recovery times of up to 20 min (compared to more typical ˜1 min recovery times). Characteristics and occurrence rates of long ionospheric recovery events on the NWC transmitter signal recorded at Malaysia are presented. 48 long recovery events were observed. The location of the causative lightning discharge for each event is determined from GLD360 and WWLLN data, and each discharge is categorized as being over land or sea. Results provide strong evidence that long recovery events are attributed predominately to lightning discharges occurring over the sea, despite the fact that lightning activity in the region is more prevalent over land. Of the 48 long recovery events, 42 were attributed to lightning activity over water. Analysis of the causative lightning of long recovery events in comparison to all early VLF events reveals that these long recovery events are detectable for lighting discharges at larger distances from the signal path, indicating a different scattering pattern for long recovery events.

A conserved signaling network monitors delivery of sphingolipids to the plasma membrane in budding yeast

PubMed Central

Clarke, Jesse; Dephoure, Noah; Horecka, Ira; Gygi, Steven; Kellogg, Douglas

2017-01-01

In budding yeast, cell cycle progression and ribosome biogenesis are dependent on plasma membrane growth, which ensures that events of cell growth are coordinated with each other and with the cell cycle. However, the signals that link the cell cycle and ribosome biogenesis to membrane growth are poorly understood. Here we used proteome-wide mass spectrometry to systematically discover signals associated with membrane growth. The results suggest that membrane trafficking events required for membrane growth generate sphingolipid-dependent signals. A conserved signaling network appears to play an essential role in signaling by responding to delivery of sphingolipids to the plasma membrane. In addition, sphingolipid-dependent signals control phosphorylation of protein kinase C (Pkc1), which plays an essential role in the pathways that link the cell cycle and ribosome biogenesis to membrane growth. Together these discoveries provide new clues as to how growth-­dependent signals control cell growth and the cell cycle. PMID:28794263

Time-Frequency Approach for Stochastic Signal Detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghosh, Ripul; Akula, Aparna; Kumar, Satish

2011-10-20

The detection of events in a stochastic signal has been a subject of great interest. One of the oldest signal processing technique, Fourier Transform of a signal contains information regarding frequency content, but it cannot resolve the exact onset of changes in the frequency, all temporal information is contained in the phase of the transform. On the other hand, Spectrogram is better able to resolve temporal evolution of frequency content, but has a trade-off in time resolution versus frequency resolution in accordance with the uncertainty principle. Therefore, time-frequency representations are considered for energetic characterisation of the non-stationary signals. Wigner Villemore » Distribution (WVD) is the most prominent quadratic time-frequency signal representation and used for analysing frequency variations in signals.WVD allows for instantaneous frequency estimation at each data point, for a typical temporal resolution of fractions of a second. This paper through simulations describes the way time frequency models are applied for the detection of event in a stochastic signal.« less

Time-Frequency Approach for Stochastic Signal Detection

NASA Astrophysics Data System (ADS)

Ghosh, Ripul; Akula, Aparna; Kumar, Satish; Sardana, H. K.

2011-10-01

The detection of events in a stochastic signal has been a subject of great interest. One of the oldest signal processing technique, Fourier Transform of a signal contains information regarding frequency content, but it cannot resolve the exact onset of changes in the frequency, all temporal information is contained in the phase of the transform. On the other hand, Spectrogram is better able to resolve temporal evolution of frequency content, but has a trade-off in time resolution versus frequency resolution in accordance with the uncertainty principle. Therefore, time-frequency representations are considered for energetic characterisation of the non-stationary signals. Wigner Ville Distribution (WVD) is the most prominent quadratic time-frequency signal representation and used for analysing frequency variations in signals.WVD allows for instantaneous frequency estimation at each data point, for a typical temporal resolution of fractions of a second. This paper through simulations describes the way time frequency models are applied for the detection of event in a stochastic signal.

Divergent β-Arrestin-dependent Signaling Events Are Dependent upon Sequences within G-protein-coupled Receptor C Termini*

PubMed Central

Pal, Kasturi; Mathur, Maneesh; Kumar, Puneet; DeFea, Kathryn

2013-01-01

β-Arrestins are multifunctional adaptor proteins that, upon recruitment to an activated G-protein-coupled receptor, can promote desensitization of G-protein signaling and receptor internalization while simultaneously eliciting an independent signal. The result of β-arrestin signaling depends upon the activating receptor. For example, activation of two Gαq-coupled receptors, protease-activated receptor-2 (PAR2) and neurokinin-1 receptor (NK1R), results in drastically different signaling events. PAR2 promotes β-arrestin-dependent membrane-sequestered extracellular signal-regulated kinase (ERK1/2) activation, cofilin activation, and cell migration, whereas NK1R promotes nuclear ERK1/2 activation and proliferation. Using bioluminescence resonance energy transfer to monitor receptor/β-arrestin interactions in real time, we observe that PAR2 has a higher apparent affinity for both β-arrestins than does NK1R, recruits them at a faster rate, and exhibits more rapid desensitization of the G-protein signal. Furthermore, recruitment of β-arrestins to PAR2 does not require prior Gαq signaling events, whereas inhibition of Gαq signaling intermediates inhibits recruitment of β-arrestins to NK1R. Using chimeric receptors in which the C terminus of PAR2 is fused to the N terminus of NK1R and vice versa and a critical Ser/Thr mutant of PAR2, we demonstrate that interactions between β-arrestins and specific phosphoresidues in the C termini of each receptor are crucial for determining the rate and magnitude of β-arrestin recruitment as well as the ultimate signaling outcome. PMID:23235155