Platform for Post-Processing Waveform-Based NDE

NASA Technical Reports Server (NTRS)

Roth, Don J.

2010-01-01

Signal- and image-processing methods are commonly needed to extract information from the waves, improve resolution of, and highlight defects in an image. Since some similarity exists for all waveform-based nondestructive evaluation (NDE) methods, it would seem that a common software platform containing multiple signal- and image-processing techniques to process the waveforms and images makes sense where multiple techniques, scientists, engineers, and organizations are involved. NDE Wave & Image Processor Version 2.0 software provides a single, integrated signal- and image-processing and analysis environment for total NDE data processing and analysis. It brings some of the most useful algorithms developed for NDE over the past 20 years into a commercial-grade product. The software can import signal/spectroscopic data, image data, and image series data. This software offers the user hundreds of basic and advanced signal- and image-processing capabilities including esoteric 1D and 2D wavelet-based de-noising, de-trending, and filtering. Batch processing is included for signal- and image-processing capability so that an optimized sequence of processing operations can be applied to entire folders of signals, spectra, and images. Additionally, an extensive interactive model-based curve-fitting facility has been included to allow fitting of spectroscopy data such as from Raman spectroscopy. An extensive joint-time frequency module is included for analysis of non-stationary or transient data such as that from acoustic emission, vibration, or earthquake data.

The Gab1 protein is a docking site for multiple proteins involved in signaling by the B cell antigen receptor.

PubMed

Ingham, R J; Holgado-Madruga, M; Siu, C; Wong, A J; Gold, M R

1998-11-13

Gab1 is a member of the docking/scaffolding protein family which includes IRS-1, IRS-2, c-Cbl, p130(cas), and p62(dok). These proteins contain a variety of protein-protein interaction motifs including multiple tyrosine residues that when phosphorylated can act as binding sites for Src homology 2 (SH2) domain-containing signaling proteins. We show in the RAMOS human B cell line that Gab1 is tyrosine-phosphorylated in response to B cell antigen receptor (BCR) engagement. Moreover, tyrosine phosphorylation of Gab1 correlated with the binding of several SH2-containing signaling proteins to Gab1 including Shc, Grb2, phosphatidylinositol 3-kinase, and the SHP-2 tyrosine phosphatase. Far Western analysis showed that the SH2 domains of Shc, SHP-2, and the p85 subunit of phosphatidylinositol 3-kinase could bind directly to tyrosine-phosphorylated Gab1 isolated from activated RAMOS cells. In contrast, the Grb2 SH2 domain did not bind directly to Gab1 but instead to the Shc and SHP-2 associated with Gab1. We also show that Gab1 is present in the membrane-enriched particulate fraction of RAMOS cells and that Gab1/signaling protein complexes are found in this fraction after BCR engagement. Thus, tyrosine-phosphorylated Gab1 may recruit cytosolic signaling proteins to cellular membranes where they can act on membrane-bound targets. This may be a critical step in the activation of multiple BCR signaling pathways.

Digital communications study

NASA Technical Reports Server (NTRS)

Boorstyn, R. R.

1973-01-01

Research is reported dealing with problems of digital data transmission and computer communications networks. The results of four individual studies are presented which include: (1) signal processing with finite state machines, (2) signal parameter estimation from discrete-time observations, (3) digital filtering for radar signal processing applications, and (4) multiple server queues where all servers are not identical.

Lateralized hippocampal oscillations underlie distinct aspects of human spatial memory and navigation.

PubMed

Miller, Jonathan; Watrous, Andrew J; Tsitsiklis, Melina; Lee, Sang Ah; Sheth, Sameer A; Schevon, Catherine A; Smith, Elliot H; Sperling, Michael R; Sharan, Ashwini; Asadi-Pooya, Ali Akbar; Worrell, Gregory A; Meisenhelter, Stephen; Inman, Cory S; Davis, Kathryn A; Lega, Bradley; Wanda, Paul A; Das, Sandhitsu R; Stein, Joel M; Gorniak, Richard; Jacobs, Joshua

2018-06-21

The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including both left and right hippocampi, and we use spectral analysis to identify oscillatory patterns related to memory encoding and navigation. We show that in the left but not right hippocampus, the amplitude of oscillations in the 1-3-Hz "low theta" band increases when viewing subsequently remembered object-location pairs. In contrast, in the right but not left hippocampus, low-theta activity increases during periods of navigation. The frequencies of these hippocampal signals are slower than task-related signals in the neocortex. These results suggest that the human brain includes multiple lateralized oscillatory networks that support different aspects of cognition.

Introduction to acoustic emission

NASA Technical Reports Server (NTRS)

Possa, G.

1983-01-01

Typical acoustic emission signal characteristics are described and techniques which localize the signal source by processing the acoustic delay data from multiple sensors are discussed. The instrumentation, which includes sensors, amplifiers, pulse counters, a minicomputer and output devices is examined. Applications are reviewed.

Global interrupt and barrier networks

DOEpatents

Blumrich, Matthias A.; Chen, Dong; Coteus, Paul W.; Gara, Alan G.; Giampapa, Mark E; Heidelberger, Philip; Kopcsay, Gerard V.; Steinmacher-Burow, Burkhard D.; Takken, Todd E.

2008-10-28

A system and method for generating global asynchronous signals in a computing structure. Particularly, a global interrupt and barrier network is implemented that implements logic for generating global interrupt and barrier signals for controlling global asynchronous operations performed by processing elements at selected processing nodes of a computing structure in accordance with a processing algorithm; and includes the physical interconnecting of the processing nodes for communicating the global interrupt and barrier signals to the elements via low-latency paths. The global asynchronous signals respectively initiate interrupt and barrier operations at the processing nodes at times selected for optimizing performance of the processing algorithms. In one embodiment, the global interrupt and barrier network is implemented in a scalable, massively parallel supercomputing device structure comprising a plurality of processing nodes interconnected by multiple independent networks, with each node including one or more processing elements for performing computation or communication activity as required when performing parallel algorithm operations. One multiple independent network includes a global tree network for enabling high-speed global tree communications among global tree network nodes or sub-trees thereof. The global interrupt and barrier network may operate in parallel with the global tree network for providing global asynchronous sideband signals.

Fibroblast growth factors, old kids on the new block

PubMed Central

Li, Xiaokun; Wang, Cong; Xiao, Jian; McKeehan, Wallace L.; Wang, Fen

2016-01-01

The fibroblast growth factors (FGFs) are a family of cell intrinsic regulatory peptides that control a broad spectrum of cellular activities. The family includes canonic FGFs that elicit their activities by activating the FGF receptor (FGFR) tyrosine kinase and non-canonic members that elicit their activities intracellularly and via FGFR-independent mechanisms. The FGF signaling axis is highly complex due to the existence of multiple isoforms of both ligands and receptors, as well as cofactors that include the chemically heterogeneous heparan sulfate (HS) cofactors, and in the case of endocrine FGFs, the Klotho coreceptors. Resident FGF signaling controls embryonic development, maintains tissue homeostasis, promotes wound healing and tissue regeneration, and regulates functions of multiple organs. However, ectopic or aberrant FGF signaling is a culprit for various diseases, including congenital birth defects, metabolic disorder, and cancer. The molecular mechanisms by which the specificity of FGF signaling is achieved remain incompletely understood. Since its application as a druggable target has been gradually recognized by pharmaceutical companies and translational researchers, understanding the determinants of FGF signaling specificity has become even more important in order to get into the position to selectively suppress a particular pathway without affecting others to minimize side effects. PMID:26768548

Dynamic regulation of genetic pathways and targets during aging in Caenorhabditis elegans.

PubMed

He, Kan; Zhou, Tao; Shao, Jiaofang; Ren, Xiaoliang; Zhao, Zhongying; Liu, Dahai

2014-03-01

Numerous genetic targets and some individual pathways associated with aging have been identified using the worm model. However, less is known about the genetic mechanisms of aging in genome wide, particularly at the level of multiple pathways as well as the regulatory networks during aging. Here, we employed the gene expression datasets of three time points during aging in Caenorhabditis elegans (C. elegans) and performed the approach of gene set enrichment analysis (GSEA) on each dataset between adjacent stages. As a result, multiple genetic pathways and targets were identified as significantly down- or up-regulated. Among them, 5 truly aging-dependent signaling pathways including MAPK signaling pathway, mTOR signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway and ErbB signaling pathway as well as 12 significantly associated genes were identified with dynamic expression pattern during aging. On the other hand, the continued declines in the regulation of several metabolic pathways have been demonstrated to display age-related changes. Furthermore, the reconstructed regulatory networks based on three of aging related Chromatin immunoprecipitation experiments followed by sequencing (ChIP-seq) datasets and the expression matrices of 154 involved genes in above signaling pathways provide new insights into aging at the multiple pathways level. The combination of multiple genetic pathways and targets needs to be taken into consideration in future studies of aging, in which the dynamic regulation would be uncovered.

Occupant traffic estimation through structural vibration sensing

NASA Astrophysics Data System (ADS)

Pan, Shijia; Mirshekari, Mostafa; Zhang, Pei; Noh, Hae Young

2016-04-01

The number of people passing through different indoor areas is useful in various smart structure applications, including occupancy-based building energy/space management, marketing research, security, etc. Existing approaches to estimate occupant traffic include vision-, sound-, and radio-based (mobile) sensing methods, which have placement limitations (e.g., requirement of line-of-sight, quiet environment, carrying a device all the time). Such limitations make these direct sensing approaches difficult to deploy and maintain. An indirect approach using geophones to measure floor vibration induced by footsteps can be utilized. However, the main challenge lies in distinguishing multiple simultaneous walkers by developing features that can effectively represent the number of mixed signals and characterize the selected features under different traffic conditions. This paper presents a method to monitor multiple persons. Once the vibration signals are obtained, features are extracted to describe the overlapping vibration signals induced by multiple footsteps, which are used for occupancy traffic estimation. In particular, we focus on analysis of the efficiency and limitations of the four selected key features when used for estimating various traffic conditions. We characterize these features with signals collected from controlled impulse load tests as well as from multiple people walking through a real-world sensing area. In our experiments, the system achieves the mean estimation error of +/-0.2 people for different occupant traffic conditions (from one to four) using k-nearest neighbor classifier.

A Macroevolutionary Perspective on Multiple Sexual Traits in the Phasianidae (Galliformes)

PubMed Central

Kimball, Rebecca T.; Mary, Colette M. St.; Braun, Edward L.

2011-01-01

Traits involved in sexual signaling are ubiquitous among animals. Although a single trait appears sufficient to convey information, many sexually dimorphic species exhibit multiple sexual signals, which may be costly to signalers and receivers. Given that one signal may be enough, there are many microevolutionary hypotheses to explain the evolution of multiple signals. Here we extend these hypotheses to a macroevolutionary scale and compare those predictions to the patterns of gains and losses of sexual dimorphism in pheasants and partridges. Among nine dimorphic characters, including six intersexual signals and three indicators of competitive ability, all exhibited both gains and losses of dimorphism within the group. Although theories of intersexual selection emphasize gain and elaboration, those six characters exhibited greater rates of loss than gain; in contrast, the competitive traits showed a slight bias towards gains. The available models, when examined in a macroevolutionary framework, did not yield unique predictions, making it difficult to distinguish among them. Even with this limitation, when the predictions of these alternative models were compared with the heterogeneous patterns of evolution of dimorphism in phasianids, it is clear that many different selective processes have been involved in the evolution of sexual signals in this group. PMID:21716735

Portable multiplicity counter

DOEpatents

Newell, Matthew R [Los Alamos, NM; Jones, David Carl [Los Alamos, NM

2009-09-01

A portable multiplicity counter has signal input circuitry, processing circuitry and a user/computer interface disposed in a housing. The processing circuitry, which can comprise a microcontroller integrated circuit operably coupled to shift register circuitry implemented in a field programmable gate array, is configured to be operable via the user/computer interface to count input signal pluses receivable at said signal input circuitry and record time correlations thereof in a total counting mode, coincidence counting mode and/or a multiplicity counting mode. The user/computer interface can be for example an LCD display/keypad and/or a USB interface. The counter can include a battery pack for powering the counter and low/high voltage power supplies for biasing external detectors so that the counter can be configured as a hand-held device for counting neutron events.

Acceleration Recorder and Playback Module

NASA Technical Reports Server (NTRS)

Bozeman, Richard J., Jr. (Inventor)

1996-01-01

The present invention is directed to methods and apparatus relating to an accelerometer electrical signal recorder and playback module. The recorder module may be manufactured in lightweight configuration and includes analog memory components to store data. Signal conditioning circuitry is incorporated into the module so that signals may be connected directly from the accelerometer to the recorder module. A battery pack may be included for powering both the module and the accelerometer. Timing circuitry is included to control the time duration within which data is recorded or played back so as to avoid overloading the analog memory components. Multiple accelerometer signal recordings may be taken simultaneously without analog to digital circuits, multiplexing circuitry or software to compensate for the effects of multiplexing the signals.

Acceleration recorder and playback module

NASA Astrophysics Data System (ADS)

Bozeman, Richard J., Jr.

1994-11-01

The present invention is directed to methods and apparatus relating to an accelerometer electrical signal recorder and playback module. The recorder module may be manufactured in lightweight configuration and includes analog memory components to store data. Signal conditioning circuitry is incorporated into the module so that signals may be connected directly from the accelerometer to the recorder module. A battery pack may be included for powering both the module and the accelerometer. Timing circuitry is included to control the time duration within which data is recorded or played back so as to avoid overloading the analog memory components. Multiple accelerometer signal recordings may be taken simultaneously without analog to digital circuits, multiplexing circuitry or software to compensate for the effects of multiplexing the signals.

Acceleration recorder and playback module

NASA Astrophysics Data System (ADS)

Bozeman, Richard J., Jr.

1992-09-01

The present invention is directed to methods and apparatus relating to an accelerometer electrical signal recorder and playback module. The recorder module may be manufactured in lightweight configuration and includes analog memory components to store data. Signal conditioning circuitry is incorporated into the module so that signals may be connected directly from the accelerometer to the recorder module. A battery pack may be included for powering both the module and the accelerometer. Timing circuitry is included to control the time duration within which data is recorded or played back so as to avoid overloading the analog memory components. Multiple accelerometer signal recordings may be taken simultaneously without analog to digital circuits, multiplexing circuitry or software to compensate for the effects of multiplexing the signals.

Acceleration recorder and playback module

NASA Technical Reports Server (NTRS)

Bozeman, Richard J., Jr. (Inventor)

1994-01-01

The present invention is directed to methods and apparatus relating to an accelerometer electrical signal recorder and playback module. The recorder module may be manufactured in lightweight configuration and includes analog memory components to store data. Signal conditioning circuitry is incorporated into the module so that signals may be connected directly from the accelerometer to the recorder module. A battery pack may be included for powering both the module and the accelerometer. Timing circuitry is included to control the time duration within which data is recorded or played back so as to avoid overloading the analog memory components. Multiple accelerometer signal recordings may be taken simultaneously without analog to digital circuits, multiplexing circuitry or software to compensate for the effects of multiplexing the signals.

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 ...

Modulation of C. elegans Touch Sensitivity Is Integrated at Multiple Levels

PubMed Central

Chen, Xiaoyin

2014-01-01

Sensory systems can adapt to different environmental signals. Here we identify four conditions that modulate anterior touch sensitivity in Caenorhabditis elegans after several hours and demonstrate that such sensory modulation is integrated at multiple levels to produce a single output. Prolonged vibration involving integrin signaling directly sensitizes the touch receptor neurons (TRNs). In contrast, hypoxia, the dauer state, and high salt reduce touch sensitivity by preventing the release of long-range neuroregulators, including two insulin-like proteins. Integration of these latter inputs occurs at upstream neurohormonal cells and at the insulin signaling cascade within the TRNs. These signals and those from integrin signaling converge to modulate touch sensitivity by regulating AKT kinases and DAF-16/FOXO. Thus, activation of either the integrin or insulin pathways can compensate for defects in the other pathway. This modulatory system integrates conflicting signals from different modalities, and adapts touch sensitivity to both mechanical and non-mechanical conditions. PMID:24806678

High Spectral Resolution Lidar Measurements of Multiple Scattering

NASA Technical Reports Server (NTRS)

Eloranta, E. W.; Piironen, P.

1996-01-01

The University of Wisconsin High Spectral Resolution Lidar (HSRL) provides unambiguous measurements of backscatter cross section, backscatter phase function, depolarization, and optical depth. This is accomplished by dividing the lidar return into separate particulate and molecular contributions. The molecular return is then used as a calibration target. We have modified the HSRL to use an I2 molecular absorption filter to separate aerosol and molecular signals. This allows measurement in dense clouds. Useful profiles extend above the cloud base until the two way optical depth reaches values between 5 and 6; beyond this, photon counting errors become large. In order to observe multiple scattering, the HSRL includes a channel which records the combined aerosol and molecular lidar return simultaneously with the spectrometer channel measurements of optical properties. This paper describes HSRL multiple scattering measurements from both water and ice clouds. These include signal strengths and depolarizations as a function of receiver field of view. All observations include profiles of extinction and backscatter cross sections. Measurements are also compared to predictions of a multiple scattering model based on small angle approximations.

Wide bandwidth phase-locked loop circuit

NASA Technical Reports Server (NTRS)

Koudelka, Robert David (Inventor)

2005-01-01

A PLL circuit uses a multiple frequency range PLL in order to phase lock input signals having a wide range of frequencies. The PLL includes a VCO capable of operating in multiple different frequency ranges and a divider bank independently configurable to divide the output of the VCO. A frequency detector detects a frequency of the input signal and a frequency selector selects an appropriate frequency range for the PLL. The frequency selector automatically switches the PLL to a different frequency range as needed in response to a change in the input signal frequency. Frequency range hysteresis is implemented to avoid operating the PLL near a frequency range boundary.

Communications interface for wireless communications headset

NASA Technical Reports Server (NTRS)

Culotta, Jr., Anthony Joseph (Inventor); Seibert, Marc A. (Inventor)

2004-01-01

A universal interface adapter circuit interfaces, for example, a wireless communications headset with any type of communications system, including those that require push-to-talk (PTT) signaling. The interface adapter is comprised of several main components, including an RF signaling receiver, a microcontroller and associated circuitry for decoding and processing the received signals, and programmable impedance matching and line interfacing circuitry for interfacing a wireless communications headset system base to a communications system. A signaling transmitter, which is preferably portable (e.g., handheld), is employed by the wireless headset user to send signals to the signaling receiver. In an embodiment of the invention directed specifically to push-to-talk (PTT) signaling, the wireless headset user presses a button on the signaling transmitter when they wish to speak. This sends a signal to the microcontroller which decodes the signal and recognizes the signal as being a PTT request. In response, the microcontroller generates a control signal that closes a switch to complete a voice connection between the headset system base and the communications system so that the user can communicate with the communications system. With this arrangement, the wireless headset can be interfaced to any communications system that requires PTT signaling, without modification of the headset device. In addition, the interface adapter can also be configured to respond to or deliver any other types of signals, such as dual-tone-multiple-frequency (DTMF) tones, and on/off hook signals. The present invention is also scalable, and permits multiple wireless users to operate independently in the same environment through use of a plurality of the interface adapters.

Brillouin Amplification--A Powerful New Scheme for Microwave Photonic Communications

NASA Technical Reports Server (NTRS)

Yao, S.; Maleki, L.

1997-01-01

We introduce the Brillouin selective sideband amplification technique and demonstrate many important applications of this technique in photonic microwave systems, including efficient phase modulation to amplitude modulation conversion, photonic frequency multiplication, photonic signal mixing with gain, and frequency multiplied signal up conversion.

Estimating respiratory rate from FBG optical sensors by using signal quality measurement.

PubMed

Yongwei Zhu; Maniyeri, Jayachandran; Fook, Victor Foo Siang; Haihong Zhang

2015-08-01

Non-intrusiveness is one of the advantages of in-bed optical sensor device for monitoring vital signs, including heart rate and respiratory rate. Estimating respiratory rate reliably using such sensors, however, is challenging, due to body movement, signal variation according to different subjects or body positions, etc. This paper presents a method for reliable respiratory rate estimation for FBG optical sensors by introducing signal quality estimation. The method estimates the quality of the signal waveform by detecting regularly repetitive patterns using proposed spectrum and cepstrum analysis. Multiple window sizes are used to cater for a wide range of target respiratory rates. Furthermore, the readings of multiple sensors are fused to derive a final respiratory rate. Experiments with 12 subjects and 2 body positions were conducted using polysomnography belt signal as groundtruth. The results demonstrated the effectiveness of the method.

International Union of Basic and Clinical Pharmacology. XCVII. G Protein–Coupled Estrogen Receptor and Its Pharmacologic Modulators

PubMed Central

2015-01-01

Estrogens are critical mediators of multiple and diverse physiologic effects throughout the body in both sexes, including the reproductive, cardiovascular, endocrine, nervous, and immune systems. As such, alterations in estrogen function play important roles in many diseases and pathophysiological conditions (including cancer), exemplified by the lower prevalence of many diseases in premenopausal women. Estrogens mediate their effects through multiple cellular receptors, including the nuclear receptor family (ERα and ERβ) and the G protein–coupled receptor (GPCR) family (GPR30/G protein–coupled estrogen receptor [GPER]). Although both receptor families can initiate rapid cell signaling and transcriptional regulation, the nuclear receptors are traditionally associated with regulating gene expression, whereas GPCRs are recognized as mediating rapid cellular signaling. Estrogen-activated pathways are not only the target of multiple therapeutic agents (e.g., tamoxifen, fulvestrant, raloxifene, and aromatase inhibitors) but are also affected by a plethora of phyto- and xeno-estrogens (e.g., genistein, coumestrol, bisphenol A, dichlorodiphenyltrichloroethane). Because of the existence of multiple estrogen receptors with overlapping ligand specificities, expression patterns, and signaling pathways, the roles of the individual receptors with respect to the diverse array of endogenous and exogenous ligands have been challenging to ascertain. The identification of GPER-selective ligands however has led to a much greater understanding of the roles of this receptor in normal physiology and disease as well as its interactions with the classic estrogen receptors ERα and ERβ and their signaling pathways. In this review, we describe the history and characterization of GPER over the past 15 years focusing on the pharmacology of steroidal and nonsteroidal compounds that have been employed to unravel the biology of this most recently recognized estrogen receptor. PMID:26023144

International Union of Basic and Clinical Pharmacology. XCVII. G Protein-Coupled Estrogen Receptor and Its Pharmacologic Modulators.

PubMed

Prossnitz, Eric R; Arterburn, Jeffrey B

2015-07-01

Estrogens are critical mediators of multiple and diverse physiologic effects throughout the body in both sexes, including the reproductive, cardiovascular, endocrine, nervous, and immune systems. As such, alterations in estrogen function play important roles in many diseases and pathophysiological conditions (including cancer), exemplified by the lower prevalence of many diseases in premenopausal women. Estrogens mediate their effects through multiple cellular receptors, including the nuclear receptor family (ERα and ERβ) and the G protein-coupled receptor (GPCR) family (GPR30/G protein-coupled estrogen receptor [GPER]). Although both receptor families can initiate rapid cell signaling and transcriptional regulation, the nuclear receptors are traditionally associated with regulating gene expression, whereas GPCRs are recognized as mediating rapid cellular signaling. Estrogen-activated pathways are not only the target of multiple therapeutic agents (e.g., tamoxifen, fulvestrant, raloxifene, and aromatase inhibitors) but are also affected by a plethora of phyto- and xeno-estrogens (e.g., genistein, coumestrol, bisphenol A, dichlorodiphenyltrichloroethane). Because of the existence of multiple estrogen receptors with overlapping ligand specificities, expression patterns, and signaling pathways, the roles of the individual receptors with respect to the diverse array of endogenous and exogenous ligands have been challenging to ascertain. The identification of GPER-selective ligands however has led to a much greater understanding of the roles of this receptor in normal physiology and disease as well as its interactions with the classic estrogen receptors ERα and ERβ and their signaling pathways. In this review, we describe the history and characterization of GPER over the past 15 years focusing on the pharmacology of steroidal and nonsteroidal compounds that have been employed to unravel the biology of this most recently recognized estrogen receptor. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Electrophysiological Signals of Familiarity and Recency in the Infant Brain

ERIC Educational Resources Information Center

Snyder, Kelly A.; Garza, John; Zolot, Liza; Kresse, Anna

2010-01-01

Electrophysiological work in nonhuman primates has established the existence of multiple types of signals in the temporal lobe that contribute to recognition memory, including information regarding a stimulus's relative novelty, familiarity, and recency of occurrence. We used high-density event-related potentials (ERPs) to examine whether young…

Acute carbon dioxide avoidance in Caenorhabditis elegans

PubMed Central

Hallem, Elissa A.; Sternberg, Paul W.

2008-01-01

Carbon dioxide is produced as a by-product of cellular respiration by all aerobic organisms and thus serves for many animals as an important indicator of food, mates, and predators. However, whether free-living terrestrial nematodes such as Caenorhabditis elegans respond to CO2 was unclear. We have demonstrated that adult C. elegans display an acute avoidance response upon exposure to CO2 that is characterized by the cessation of forward movement and the rapid initiation of backward movement. This response is mediated by a cGMP signaling pathway that includes the cGMP-gated heteromeric channel TAX-2/TAX-4. CO2 avoidance is modulated by multiple signaling molecules, including the neuropeptide Y receptor NPR-1 and the calcineurin subunits TAX-6 and CNB-1. Nutritional status also modulates CO2 responsiveness via the insulin and TGFβ signaling pathways. CO2 response is mediated by a neural circuit that includes the BAG neurons, a pair of sensory neurons of previously unknown function. TAX-2/TAX-4 function in the BAG neurons to mediate acute CO2 avoidance. Our results demonstrate that C. elegans senses and responds to CO2 using multiple signaling pathways and a neural network that includes the BAG neurons and that this response is modulated by the physiological state of the worm. PMID:18524955

Acute carbon dioxide avoidance in Caenorhabditis elegans.

PubMed

Hallem, Elissa A; Sternberg, Paul W

2008-06-10

Carbon dioxide is produced as a by-product of cellular respiration by all aerobic organisms and thus serves for many animals as an important indicator of food, mates, and predators. However, whether free-living terrestrial nematodes such as Caenorhabditis elegans respond to CO2 was unclear. We have demonstrated that adult C. elegans display an acute avoidance response upon exposure to CO2 that is characterized by the cessation of forward movement and the rapid initiation of backward movement. This response is mediated by a cGMP signaling pathway that includes the cGMP-gated heteromeric channel TAX-2/TAX-4. CO2 avoidance is modulated by multiple signaling molecules, including the neuropeptide Y receptor NPR-1 and the calcineurin subunits TAX-6 and CNB-1. Nutritional status also modulates CO2 responsiveness via the insulin and TGFbeta signaling pathways. CO2 response is mediated by a neural circuit that includes the BAG neurons, a pair of sensory neurons of previously unknown function. TAX-2/TAX-4 function in the BAG neurons to mediate acute CO2 avoidance. Our results demonstrate that C. elegans senses and responds to CO2 using multiple signaling pathways and a neural network that includes the BAG neurons and that this response is modulated by the physiological state of the worm.

Multiple resolution chirp reflectometry for fault localization and diagnosis in a high voltage cable in automotive electronics

NASA Astrophysics Data System (ADS)

Chang, Seung Jin; Lee, Chun Ku; Shin, Yong-June; Park, Jin Bae

2016-12-01

A multiple chirp reflectometry system with a fault estimation process is proposed to obtain multiple resolution and to measure the degree of fault in a target cable. A multiple resolution algorithm has the ability to localize faults, regardless of fault location. The time delay information, which is derived from the normalized cross-correlation between the incident signal and bandpass filtered reflected signals, is converted to a fault location and cable length. The in-phase and quadrature components are obtained by lowpass filtering of the mixed signal of the incident signal and the reflected signal. Based on in-phase and quadrature components, the reflection coefficient is estimated by the proposed fault estimation process including the mixing and filtering procedure. Also, the measurement uncertainty for this experiment is analyzed according to the Guide to the Expression of Uncertainty in Measurement. To verify the performance of the proposed method, we conduct comparative experiments to detect and measure faults under different conditions. Considering the installation environment of the high voltage cable used in an actual vehicle, target cable length and fault position are designed. To simulate the degree of fault, the variety of termination impedance (10 Ω , 30 Ω , 50 Ω , and 1 \\text{k} Ω ) are used and estimated by the proposed method in this experiment. The proposed method demonstrates advantages in that it has multiple resolution to overcome the blind spot problem, and can assess the state of the fault.

Multiple signals at the extended 8p23 locus are associated with susceptibility to systemic lupus erythematosus.

PubMed

Demirci, F Yesim; Wang, Xingbin; Morris, David L; Feingold, Eleanor; Bernatsky, Sasha; Pineau, Christian; Clarke, Ann; Ramsey-Goldman, Rosalind; Manzi, Susan; Vyse, Timothy J; Kamboh, M I

2017-06-01

A major systemic lupus erythematosus (SLE) susceptibility locus lies within a common inversion polymorphism region (encompassing 3.8 - 4.5  Mb) located at 8p23. Initially implicated genes included FAM167A-BLK and XKR6 , of which BLK received major attention due to its known role in B-cell biology. Recently, additional SLE risk carried in non-inverted background was also reported. In this case -control study, we further investigated the 'extended' 8p23 locus (~ 4  Mb) where we observed multiple SLE signals and assessed these signals for their relation to the inversion affecting this region. The study involved a North American discovery data set ( ~ 1200  subjects) and a replication data set (> 10 000  subjects) comprising European-descent individuals. Meta-analysis of 8p23 SNPs, with p < 0.05 in both data sets, identified 51 genome-wide significant SNPs (p < 5.0 × 10 -8 ). While most of these SNPs were related to previously implicated signals ( XKR6-FAM167A-BLK subregion), our results also revealed two 'new' SLE signals, including SGK223-CLDN23-MFHAS1 (6.06 × 10 -9 ≤ meta p ≤ 4.88 × 10 -8 ) and CTSB (meta p = 4.87 × 10 -8 ) subregions that are located > 2 Mb upstream and ~ 0.3  Mb downstream from previously reported signals. Functional assessment of relevant SNPs indicated putative cis -effects on the expression of various genes at 8p23. Additional analyses in discovery sample, where the inversion genotypes were inferred, replicated the association of non-inverted status with SLE risk and suggested that a number of SLE risk alleles are predominantly carried in non-inverted background. Our results implicate multiple (known+novel) SLE signals/genes at the extended 8p23 locus, beyond previously reported signals/genes, and suggest that this broad locus contributes to SLE risk through the effects of multiple genes/pathways. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

High temperature ion channels and pores

NASA Technical Reports Server (NTRS)

Cheley, Stephen (Inventor); Gu, Li Qun (Inventor); Bayley, Hagan (Inventor); Kang, Xiaofeng (Inventor)

2011-01-01

The present invention includes an apparatus, system and method for stochastic sensing of an analyte to a protein pore. The protein pore may be an engineer protein pore, such as an ion channel at temperatures above 55.degree. C. and even as high as near 100.degree. C. The analyte may be any reactive analyte, including chemical weapons, environmental toxins and pharmaceuticals. The analyte covalently bonds to the sensor element to produce a detectable electrical current signal. Possible signals include change in electrical current. Detection of the signal allows identification of the analyte and determination of its concentration in a sample solution. Multiple analytes present in the same solution may also be detected.

Loss of Pancreas upon Activated Wnt Signaling Is Concomitant with Emergence of Gastrointestinal Identity

PubMed Central

Herrero-Martin, Griselda; Puri, Sapna; Taketo, Makoto Mark; Rojas, Anabel; Hebrok, Matthias; Cano, David A.

2016-01-01

Organ formation is achieved through the complex interplay between signaling pathways and transcriptional cascades. The canonical Wnt signaling pathway plays multiple roles during embryonic development including patterning, proliferation and differentiation in distinct tissues. Previous studies have established the importance of this pathway at multiple stages of pancreas formation as well as in postnatal organ function and homeostasis. In mice, gain-of-function experiments have demonstrated that activation of the canonical Wnt pathway results in pancreatic hypoplasia, a phenomenon whose underlying mechanisms remains to be elucidated. Here, we show that ectopic activation of epithelial canonical Wnt signaling causes aberrant induction of gastric and intestinal markers both in the pancreatic epithelium and mesenchyme, leading to the development of gut-like features. Furthermore, we provide evidence that β -catenin-induced impairment of pancreas formation depends on Hedgehog signaling. Together, our data emphasize the developmental plasticity of pancreatic progenitors and further underscore the key role of precise regulation of signaling pathways to maintain appropriate organ boundaries. PMID:27736991

Roles of mTOR Signaling in Brain Development.

PubMed

Lee, Da Yong

2015-09-01

mTOR is a serine/threonine kinase composed of multiple protein components. Intracellular signaling of mTOR complexes is involved in many of physiological functions including cell survival, proliferation and differentiation through the regulation of protein synthesis in multiple cell types. During brain development, mTOR-mediated signaling pathway plays a crucial role in the process of neuronal and glial differentiation and the maintenance of the stemness of neural stem cells. The abnormalities in the activity of mTOR and its downstream signaling molecules in neural stem cells result in severe defects of brain developmental processes causing a significant number of brain disorders, such as pediatric brain tumors, autism, seizure, learning disability and mental retardation. Understanding the implication of mTOR activity in neural stem cells would be able to provide an important clue in the development of future brain developmental disorder therapies.

NITRIC OXIDE, MITOCHONDRIAL HYPERPOLARIZATION AND T-CELL ACTIVATION

PubMed Central

Nagy, Gyorgy; Koncz, Agnes; Fernandez, David; Perl, Andras

2007-01-01

T lymphocyte activation is associated with nitric oxide (NO) production that plays an essential role in multiple T cell functions. NO acts as a messenger, activating soluble guanyl cyclase and participating in the transduction signaling pathways involving cyclic GMP. NO modulates mitochondrial events that are involved in apoptosis and regulates mitochondrial membrane potential and mitochondrial biogenesis in many cell types, including lymphocytes. Mitochondrial hyperpolarization (MHP), an early and reversible event during both T lymphocyte activation and apoptosis, is regulated by NO. Here, we discuss recent evidence that NO-induced MHP represents a molecular switch in multiple T cell signaling pathways. Overproduction of NO in systemic lupus erythematosus (SLE) induces mitochondrial biogenesis and alters Ca2+ signaling. Thus, while NO plays a physiological role in lymphocyte cell signaling, its overproduction may disturb normal T cell function, contributing to the pathogenesis of autoimmunity. PMID:17462531

Interferometric Polarization Control

NASA Technical Reports Server (NTRS)

Wollack, Edward J. (Inventor); Moseley, Samuel H. (Inventor); Chuss, David T. (Inventor); Novak, Giles A. (Inventor)

2008-01-01

A signal conditioning module provides a polarimeter capability in a photometric system. The module may include multiple variable delay polarization modulators. Each modulator may include an input port, and a first arm formed to include a first reflector and first rooftop mirror arranged in opposed relationship. The first reflector may direct an input radiation signal to the first rooftop mirror. Each modulator also may include an output port and a second arm formed to include a second reflector and second rooftop mirror arranged in opposed relationship. The second reflector can guide a signal from the second rooftop mirror towards the output port to provide an output radiation signal. A beamsplitting grid may be placed between the first reflector and the first rooftop mirror, and also between the second reflector and the second rooftop mirror. A translation apparatus can provide adjustment relative to optical path length vis-a-vis the first arm, the second arm and the grid.

Interferometric polarization control

NASA Technical Reports Server (NTRS)

Wollack, Edward J. (Inventor); Novak, Giles A. (Inventor); Moseley, Samuel H. (Inventor); Chuss, David T. (Inventor)

2009-01-01

A signal conditioning module provides a polarimeter capability in a photometric system. The module may include multiple variable delay polarization modulators. Each modulator may include an input port, and a first arm formed to include a first reflector and first rooftop mirror arranged in opposed relationship. The first reflector may direct an input radiation signal to the first rooftop mirror. Each modulator also may include an output port and a second arm formed to include a second reflector and second rooftop mirror arranged in opposed relationship. The second reflector can guide a signal from the second rooftop mirror towards the output port to provide an output radiation signal. A beamsplitting grid may be placed between the first reflector and the first rooftop mirror, and also between the second reflector and the second rooftop mirror. A translation apparatus can provide adjustment relative to optical path length vis-a-vis the first arm, the second arm and the grid.

Supporting Multimedia Learning with Visual Signalling and Animated Pedagogical Agent: Moderating Effects of Prior Knowledge

ERIC Educational Resources Information Center

Johnson, A. M.; Ozogul, G.; Reisslein, M.

2015-01-01

An experiment examined the effects of visual signalling to relevant information in multiple external representations and the visual presence of an animated pedagogical agent (APA). Students learned electric circuit analysis using a computer-based learning environment that included Cartesian graphs, equations and electric circuit diagrams. The…

40 CFR 86.004-40 - Heavy-duty engine rebuilding practices.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., replacement of multiple parts due to wear, and reassembly, and also may include the removal of the engine from..., emissions-related codes or signals from on-board monitoring systems may not be erased or reset without... signals may not be rendered inoperative during the rebuilding process. (d) When conducting a rebuild...

40 CFR 86.004-40 - Heavy-duty engine rebuilding practices.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., replacement of multiple parts due to wear, and reassembly, and also may include the removal of the engine from..., emissions-related codes or signals from on-board monitoring systems may not be erased or reset without... signals may not be rendered inoperative during the rebuilding process. (d) When conducting a rebuild...

40 CFR 86.004-40 - Heavy-duty engine rebuilding practices.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., replacement of multiple parts due to wear, and reassembly, and also may include the removal of the engine from..., emissions-related codes or signals from on-board monitoring systems may not be erased or reset without... signals may not be rendered inoperative during the rebuilding process. (d) When conducting a rebuild...

40 CFR 86.004-40 - Heavy-duty engine rebuilding practices.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., replacement of multiple parts due to wear, and reassembly, and also may include the removal of the engine from..., emissions-related codes or signals from on-board monitoring systems may not be erased or reset without... signals may not be rendered inoperative during the rebuilding process. (d) When conducting a rebuild...

Multimodal optical imaging system for in vivo investigation of cerebral oxygen delivery and energy metabolism

PubMed Central

Yaseen, Mohammad A.; Srinivasan, Vivek J.; Gorczynska, Iwona; Fujimoto, James G.; Boas, David A.; Sakadžić, Sava

2015-01-01

Improving our understanding of brain function requires novel tools to observe multiple physiological parameters with high resolution in vivo. We have developed a multimodal imaging system for investigating multiple facets of cerebral blood flow and metabolism in small animals. The system was custom designed and features multiple optical imaging capabilities, including 2-photon and confocal lifetime microscopy, optical coherence tomography, laser speckle imaging, and optical intrinsic signal imaging. Here, we provide details of the system’s design and present in vivo observations of multiple metrics of cerebral oxygen delivery and energy metabolism, including oxygen partial pressure, microvascular blood flow, and NADH autofluorescence. PMID:26713212

Monitoring and predicting cognitive state and performance via physiological correlates of neuronal signals.

PubMed

Russo, Michael B; Stetz, Melba C; Thomas, Maria L

2005-07-01

Judgment, decision making, and situational awareness are higher-order mental abilities critically important to operational cognitive performance. Higher-order mental abilities rely on intact functioning of multiple brain regions, including the prefrontal, thalamus, and parietal areas. Real-time monitoring of individuals for cognitive performance capacity via an approach based on sampling multiple neurophysiologic signals and integrating those signals with performance prediction models potentially provides a method of supporting warfighters' and commanders' decision making and other operationally relevant mental processes and is consistent with the goals of augmented cognition. Cognitive neurophysiological assessments that directly measure brain function and subsequent cognition include positron emission tomography, functional magnetic resonance imaging, mass spectroscopy, near-infrared spectroscopy, magnetoencephalography, and electroencephalography (EEG); however, most direct measures are not practical to use in operational environments. More practical, albeit indirect measures that are generated by, but removed from the actual neural sources, are movement activity, oculometrics, heart rate, and voice stress signals. The goal of the papers in this section is to describe advances in selected direct and indirect cognitive neurophysiologic monitoring techniques as applied for the ultimate purpose of preventing operational performance failures. These papers present data acquired in a wide variety of environments, including laboratory, simulator, and clinical arenas. The papers discuss cognitive neurophysiologic measures such as digital signal processing wrist-mounted actigraphy; oculometrics including blinks, saccadic eye movements, pupillary movements, the pupil light reflex; and high-frequency EEG. These neurophysiological indices are related to cognitive performance as measured through standard test batteries and simulators with conditions including sleep loss, time on task, and aviation flight-induced fatigue.

Multiple disturbances classifier for electric signals using adaptive structuring neural networks

NASA Astrophysics Data System (ADS)

Lu, Yen-Ling; Chuang, Cheng-Long; Fahn, Chin-Shyurng; Jiang, Joe-Air

2008-07-01

This work proposes a novel classifier to recognize multiple disturbances for electric signals of power systems. The proposed classifier consists of a series of pipeline-based processing components, including amplitude estimator, transient disturbance detector, transient impulsive detector, wavelet transform and a brand-new neural network for recognizing multiple disturbances in a power quality (PQ) event. Most of the previously proposed methods usually treated a PQ event as a single disturbance at a time. In practice, however, a PQ event often consists of various types of disturbances at the same time. Therefore, the performances of those methods might be limited in real power systems. This work considers the PQ event as a combination of several disturbances, including steady-state and transient disturbances, which is more analogous to the real status of a power system. Six types of commonly encountered power quality disturbances are considered for training and testing the proposed classifier. The proposed classifier has been tested on electric signals that contain single disturbance or several disturbances at a time. Experimental results indicate that the proposed PQ disturbance classification algorithm can achieve a high accuracy of more than 97% in various complex testing cases.

Transmission of RF Signals Over Optical Fiber for Avionics Applications

NASA Technical Reports Server (NTRS)

Slaveski, Filip; Sluss, James, Jr.; Atiquzzaman, Mohammed; Hung, Nguyen; Ngo, Duc

2002-01-01

During flight, aircraft avionics transmit and receive RF signals to/from antennas over coaxial cables. As the density and complexity of onboard avionics increases, the electromagnetic interference (EM) environment degrades proportionately, leading to decreasing signal-to-noise ratios (SNRs) and potential safety concerns. The coaxial cables are inherently lossy, limiting the RF signal bandwidth while adding considerable weight. To overcome these limitations, we have investigated a fiber optic communications link for aircraft that utilizes wavelength division multiplexing (WDM) to support the simultaneous transmission of multiple signals (including RF) over a single optical fiber. Optical fiber has many advantages over coaxial cable, particularly lower loss, greater bandwidth, and immunity to EM. In this paper, we demonstrate that WDM can be successfully used to transmit multiple RF signals over a single optical fiber with no appreciable signal degradation. We investigate the transmission of FM and AM analog modulated signals, as well as FSK digital modulated signals, over a fiber optic link (FOL) employing WDM. We present measurements of power loss, delay, SNR, carrier-to-noise ratio (CNR), total harmonic distortion (THD), and bit error rate (BER). Our experimental results indicate that WDM is a fiber optic technology suitable for avionics applications.

Analytical multiple scattering correction to the Mie theory: Application to the analysis of the lidar signal

NASA Technical Reports Server (NTRS)

Flesia, C.; Schwendimann, P.

1992-01-01

The contribution of the multiple scattering to the lidar signal is dependent on the optical depth tau. Therefore, the radar analysis, based on the assumption that the multiple scattering can be neglected is limited to cases characterized by low values of the optical depth (tau less than or equal to 0.1) and hence it exclude scattering from most clouds. Moreover, all inversion methods relating lidar signal to number densities and particle size must be modified since the multiple scattering affects the direct analysis. The essential requests of a realistic model for lidar measurements which include the multiple scattering and which can be applied to practical situations follow. (1) Requested are not only a correction term or a rough approximation describing results of a certain experiment, but a general theory of multiple scattering tying together the relevant physical parameter we seek to measure. (2) An analytical generalization of the lidar equation which can be applied in the case of a realistic aerosol is requested. A pure analytical formulation is important in order to avoid the convergency and stability problems which, in the case of numerical approach, are due to the large number of events that have to be taken into account in the presence of large depth and/or a strong experimental noise.

Blind source separation and localization using microphone arrays

NASA Astrophysics Data System (ADS)

Sun, Longji

The blind source separation and localization problem for audio signals is studied using microphone arrays. Pure delay mixtures of source signals typically encountered in outdoor environments are considered. Our proposed approach utilizes the subspace methods, including multiple signal classification (MUSIC) and estimation of signal parameters via rotational invariance techniques (ESPRIT) algorithms, to estimate the directions of arrival (DOAs) of the sources from the collected mixtures. Since audio signals are generally considered broadband, the DOA estimates at frequencies with the large sum of squared amplitude values are combined to obtain the final DOA estimates. Using the estimated DOAs, the corresponding mixing and demixing matrices are computed, and the source signals are recovered using the inverse short time Fourier transform. Subspace methods take advantage of the spatial covariance matrix of the collected mixtures to achieve robustness to noise. While the subspace methods have been studied for localizing radio frequency signals, audio signals have their special properties. For instance, they are nonstationary, naturally broadband and analog. All of these make the separation and localization for the audio signals more challenging. Moreover, our algorithm is essentially equivalent to the beamforming technique, which suppresses the signals in unwanted directions and only recovers the signals in the estimated DOAs. Several crucial issues related to our algorithm and their solutions have been discussed, including source number estimation, spatial aliasing, artifact filtering, different ways of mixture generation, and source coordinate estimation using multiple arrays. Additionally, comprehensive simulations and experiments have been conducted to examine various aspects of the algorithm. Unlike the existing blind source separation and localization methods, which are generally time consuming, our algorithm needs signal mixtures of only a short duration and therefore supports real-time implementation.

Numerical simulations of short-mixing-time double-wave-vector diffusion-weighting experiments with multiple concatenations on whole-body MR systems

NASA Astrophysics Data System (ADS)

Finsterbusch, Jürgen

2010-12-01

Double- or two-wave-vector diffusion-weighting experiments with short mixing times in which two diffusion-weighting periods are applied in direct succession, are a promising tool to estimate cell sizes in the living tissue. However, the underlying effect, a signal difference between parallel and antiparallel wave vector orientations, is considerably reduced for the long gradient pulses required on whole-body MR systems. Recently, it has been shown that multiple concatenations of the two wave vectors in a single acquisition can double the modulation amplitude if short gradient pulses are used. In this study, numerical simulations of such experiments were performed with parameters achievable with whole-body MR systems. It is shown that the theoretical model yields a good approximation of the signal behavior if an additional term describing free diffusion is included. More importantly, it is demonstrated that the shorter gradient pulses sufficient to achieve the desired diffusion weighting for multiple concatenations, increase the signal modulation considerably, e.g. by a factor of about five for five concatenations. Even at identical echo times, achieved by a shortened diffusion time, a moderate number of concatenations significantly improves the signal modulation. Thus, experiments on whole-body MR systems may benefit from multiple concatenations.

Fluid sampling device

NASA Technical Reports Server (NTRS)

Studenick, D. K. (Inventor)

1977-01-01

An inlet leak is described for sampling gases, more specifically, for selectively sampling multiple fluids. This fluid sampling device includes a support frame. A plurality of fluid inlet devices extend through the support frame and each of the fluid inlet devices include a longitudinal aperture. An opening device that is responsive to a control signal selectively opens the aperture to allow fluid passage. A closing device that is responsive to another control signal selectively closes the aperture for terminating further fluid flow.

Single-channel mixed signal blind source separation algorithm based on multiple ICA processing

NASA Astrophysics Data System (ADS)

Cheng, Xiefeng; Li, Ji

2017-01-01

Take separating the fetal heart sound signal from the mixed signal that get from the electronic stethoscope as the research background, the paper puts forward a single-channel mixed signal blind source separation algorithm based on multiple ICA processing. Firstly, according to the empirical mode decomposition (EMD), the single-channel mixed signal get multiple orthogonal signal components which are processed by ICA. The multiple independent signal components are called independent sub component of the mixed signal. Then by combining with the multiple independent sub component into single-channel mixed signal, the single-channel signal is expanded to multipath signals, which turns the under-determined blind source separation problem into a well-posed blind source separation problem. Further, the estimate signal of source signal is get by doing the ICA processing. Finally, if the separation effect is not very ideal, combined with the last time's separation effect to the single-channel mixed signal, and keep doing the ICA processing for more times until the desired estimated signal of source signal is get. The simulation results show that the algorithm has good separation effect for the single-channel mixed physiological signals.

Metformin targets multiple signaling pathways in cancer.

PubMed

Lei, Yong; Yi, Yanhua; Liu, Yang; Liu, Xia; Keller, Evan T; Qian, Chao-Nan; Zhang, Jian; Lu, Yi

2017-01-26

Metformin, an inexpensive and well-tolerated oral agent commonly used in the first-line treatment of type 2 diabetes, has become the focus of intense research as a candidate anticancer agent. Here, we discuss the potential of metformin in cancer therapeutics, particularly its functions in multiple signaling pathways, including AMP-activated protein kinase, mammalian target of rapamycin, insulin-like growth factor, c-Jun N-terminal kinase/mitogen-activated protein kinase (p38 MAPK), human epidermal growth factor receptor-2, and nuclear factor kappaB pathways. In addition, cutting-edge targeting of cancer stem cells by metformin is summarized.

Integration of Nuclear- and Extranuclear-Initiated Estrogen Receptor Signaling in Breast Cancer Cells

ERIC Educational Resources Information Center

Madak Erdogan, Zeynep

2009-01-01

Estrogenic hormones exert their effects through binding to Estrogen Receptors (ERs), which work in concert with coregulators and extranuclear signaling pathways to control gene expression in normal as well as cancerous states, including breast tumors. In this thesis, we have used multiple genome-wide analysis tools to elucidate various ways that…

Methods for the Analysis of Protein Phosphorylation-Mediated Cellular Signaling Networks

NASA Astrophysics Data System (ADS)

White, Forest M.; Wolf-Yadlin, Alejandro

2016-06-01

Protein phosphorylation-mediated cellular signaling networks regulate almost all aspects of cell biology, including the responses to cellular stimulation and environmental alterations. These networks are highly complex and comprise hundreds of proteins and potentially thousands of phosphorylation sites. Multiple analytical methods have been developed over the past several decades to identify proteins and protein phosphorylation sites regulating cellular signaling, and to quantify the dynamic response of these sites to different cellular stimulation. Here we provide an overview of these methods, including the fundamental principles governing each method, their relative strengths and weaknesses, and some examples of how each method has been applied to the analysis of complex signaling networks. When applied correctly, each of these techniques can provide insight into the topology, dynamics, and regulation of protein phosphorylation signaling networks.

Mitochondrial Redox Signaling and Tumor Progression.

PubMed

Chen, Yuxin; Zhang, Haiqing; Zhou, Huanjiao Jenny; Ji, Weidong; Min, Wang

2016-03-25

Cancer cell can reprogram their energy production by switching mitochondrial oxidative phosphorylation to glycolysis. However, mitochondria play multiple roles in cancer cells, including redox regulation, reactive oxygen species (ROS) generation, and apoptotic signaling. Moreover, these mitochondrial roles are integrated via multiple interconnected metabolic and redox sensitive pathways. Interestingly, mitochondrial redox proteins biphasically regulate tumor progression depending on cellular ROS levels. Low level of ROS functions as signaling messengers promoting cancer cell proliferation and cancer invasion. However, anti-cancer drug-initiated stress signaling could induce excessive ROS, which is detrimental to cancer cells. Mitochondrial redox proteins could scavenger basal ROS and function as "tumor suppressors" or prevent excessive ROS to act as "tumor promoter". Paradoxically, excessive ROS often also induce DNA mutations and/or promotes tumor metastasis at various stages of cancer progression. Targeting redox-sensitive pathways and transcriptional factors in the appropriate context offers great promise for cancer prevention and therapy. However, the therapeutics should be cancer-type and stage-dependent.

Repulsive Guidance Molecules (RGMs) and Neogenin in Bone Morphogenetic Protein (BMP) signaling

PubMed Central

Tian, Chenxi; Liu, Jun

2015-01-01

Summary Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-beta (TGFβ) superfamily. BMPs mediate a highly conserved signal transduction cascade through the type I and type II serine/threonine kinase receptors and intracellular Smad proteins. The BMP pathway regulates multiple developmental and homeostatic processes. Mutations in this pathway can cause various diseases in humans, such as skeletal disorders, cardiovascular diseases and various cancers. Multiple levels of regulation, including extracellular regulation, help to ensure proper spatiotemporal control of BMP signaling in the right cellular context. The family of repulsive guidance molecules (RGMs) and the type I trans-membrane protein neogenin, a paralog of DCC (Deleted in Colorectal Cancer), have been implicated in modulating the BMP pathway. In this review, we discuss the properties and functions of RGM proteins and neogenin, focusing on their roles in the modulation of BMP signal transduction. PMID:23740870

Cognitive Neural Prosthetics

PubMed Central

Andersen, Richard A.; Hwang, Eun Jung; Mulliken, Grant H.

2010-01-01

The cognitive neural prosthetic (CNP) is a very versatile method for assisting paralyzed patients and patients with amputations. The CNP records the cognitive state of the subject, rather than signals strictly related to motor execution or sensation. We review a number of high-level cortical signals and their application for CNPs, including intention, motor imagery, decision making, forward estimation, executive function, attention, learning, and multi-effector movement planning. CNPs are defined by the cognitive function they extract, not the cortical region from which the signals are recorded. However, some cortical areas may be better than others for particular applications. Signals can also be extracted in parallel from multiple cortical areas using multiple implants, which in many circumstances can increase the range of applications of CNPs. The CNP approach relies on scientific understanding of the neural processes involved in cognition, and many of the decoding algorithms it uses also have parallels to underlying neural circuit functions. PMID:19575625

Control of proliferation and cancer growth by the Hippo signaling pathway

PubMed Central

Ehmer, Ursula; Sage, Julien

2015-01-01

The control of cell division is essential for normal development and the maintenance of cellular homeostasis. Abnormal cell proliferation is associated with multiple pathological states, including cancer. While the Hippo/YAP signaling pathway was initially thought to control organ size and growth, increasing evidence indicates that this pathway also plays a major role in the control of proliferation independent of organ size control. In particular, accumulating evidence indicates that the Hippo/YAP signaling pathway functionally interacts with multiple other cellular pathways and serves as a central node in the regulation of cell division, especially in cancer cells. Here recent observations are highlighted that connect Hippo/YAP signaling to transcription, the basic cell cycle machinery, and the control of cell division. Furthermore, the oncogenic and tumor suppressive attributes of YAP/TAZ are reviewed which emphasizes the relevance of the Hippo pathway in cancer. PMID:26432795

Ultrahigh capacity 2 × 2 MIMO RoF system at 60  GHz employing single-sideband single-carrier modulation.

PubMed

Lin, Chun-Ting; Ho, Chun-Hung; Huang, Hou-Tzu; Cheng, Yu-Hsuan

2014-03-15

This article proposes and experimentally demonstrates a radio-over-fiber system employing single-sideband single-carrier (SSB-SC) modulation at 60 GHz. SSB-SC modulation has a lower peak-to-average-power ratio than orthogonal frequency division multiplex (OFDM) modulation; therefore, the SSB-SC signals provide superior nonlinear tolerance, compared to OFDM signals. Moreover, multiple-input multiple-output (MIMO) technology was used extensively to enhance spectral efficiency. A least-mean-square-based equalizer was implemented, including MIMO channel estimation, frequency response equalization, and I/Q imbalance compensation to recover the MIMO signals. Thus, using 2×2 MIMO technology and 64-QAM SSB-SC signals, we achieved the highest data rate of 84 Gbps with 12  bit/s/Hz spectral efficiency using the 7-GHz license-free band at 60 GHz.

Classification methods to detect sleep apnea in adults based on respiratory and oximetry signals: a systematic review.

PubMed

Uddin, M B; Chow, C M; Su, S W

2018-03-26

Sleep apnea (SA), a common sleep disorder, can significantly decrease the quality of life, and is closely associated with major health risks such as cardiovascular disease, sudden death, depression, and hypertension. The normal diagnostic process of SA using polysomnography is costly and time consuming. In addition, the accuracy of different classification methods to detect SA varies with the use of different physiological signals. If an effective, reliable, and accurate classification method is developed, then the diagnosis of SA and its associated treatment will be time-efficient and economical. This study aims to systematically review the literature and present an overview of classification methods to detect SA using respiratory and oximetry signals and address the automated detection approach. Sixty-two included studies revealed the application of single and multiple signals (respiratory and oximetry) for the diagnosis of SA. Both airflow and oxygen saturation signals alone were effective in detecting SA in the case of binary decision-making, whereas multiple signals were good for multi-class detection. In addition, some machine learning methods were superior to the other classification methods for SA detection using respiratory and oximetry signals. To deal with the respiratory and oximetry signals, a good choice of classification method as well as the consideration of associated factors would result in high accuracy in the detection of SA. An accurate classification method should provide a high detection rate with an automated (independent of human action) analysis of respiratory and oximetry signals. Future high-quality automated studies using large samples of data from multiple patient groups or record batches are recommended.

Effects of Correlated and Uncorrelated Gamma Rays on Neutron Multiplicity Counting

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

Cowles, Christian C.; Behling, Richard S.; Imel, George R.

Neutron multiplicity counting relies on time correlation between neutron events to assay the fissile mass, (α,n) to spontaneous fission neutron ratio, and neutron self-multiplication of samples. Gamma-ray sensitive neutron multiplicity counters may misidentify gamma rays as neutrons and therefore miscalculate sample characteristics. Time correlated and uncorrelated gamma-ray-like signals were added into gamma-ray free neutron multiplicity counter data to examine the effects of gamma ray signals being misidentified as neutron signals on assaying sample characteristics. Multiplicity counter measurements with and without gamma-ray-like signals were compared to determine the assay error associated with gamma-ray-like signals at various gamma-ray and neutron rates. Correlatedmore » and uncorrelated gamma-ray signals each produced consistent but different measurement errors. Correlated gamma-ray signals most strongly led to fissile mass overestimates, whereas uncorrelated gamma-ray signals most strongly lead to (α,n) neutron overestimates. Gamma-ray sensitive neutron multiplicity counters may be able to account for the effects of gamma-rays on measurements to mitigate measurement uncertainties.« less

Frequency division multiplex technique

NASA Technical Reports Server (NTRS)

Brey, H. (Inventor)

1973-01-01

A system for monitoring a plurality of condition responsive devices is described. It consists of a master control station and a remote station. The master control station is capable of transmitting command signals which includes a parity signal to a remote station which transmits the signals back to the command station so that such can be compared with the original signals in order to determine if there are any transmission errors. The system utilizes frequency sources which are 1.21 multiples of each other so that no linear combination of any harmonics will interfere with another frequency.

Three-dimensional, position-sensitive radiation detection

DOEpatents

He, Zhong; Zhang, Feng

2010-04-06

Disclosed herein is a method of determining a characteristic of radiation detected by a radiation detector via a multiple-pixel event having a plurality of radiation interactions. The method includes determining a cathode-to-anode signal ratio for a selected interaction of the plurality of radiation interactions based on electron drift time data for the selected interaction, and determining the radiation characteristic for the multiple-pixel event based on both the cathode-to-anode signal ratio and the electron drift time data. In some embodiments, the method further includes determining a correction factor for the radiation characteristic based on an interaction depth of the plurality of radiation interactions, a lateral distance between the selected interaction and a further interaction of the plurality of radiation interactions, and the lateral positioning of the plurality of radiation interactions.

Method and Apparatus for Measuring Fluid Flow

NASA Technical Reports Server (NTRS)

Arndt, G. Dickey (Inventor); Nguyen, Than X. (Inventor); Carl, James R. (Inventor)

1995-01-01

The invention is a method and apparatus for monitoring the presence, concentration, and the movement of fluids. It is based on utilizing electromagnetic measurements of the complex permittivity of the fluids for detecting and monitoring the fluid. More particularly the apparatus uses one or more microwave probes which are placed at the locations where the measurements are to be made. A radio frequency signal is transmitted to the probe and the reflected signal is phase and amplitude detected at a rapid rate for the purpose of identifying the fluids, based on their dielectric constant at the probe. The apparatus can be used for multiple purposes including measures of flow rates, turbulence, dispersion, fluid identification, and changes in flow conditions of multiple fluids or multiple states of a single fluid in a flowline or a holding container. The apparatus includes a probe consisting of two electrical conductors separated by an insulator. A radio frequency signal is communicated to the probe and is reflected back from the portion of the probe exposed to the fluid. The radio frequency signal also provides a reference signal. An oscillator generates a second signal which combined with each of the reference signal and the reflected signal to produce signals of lower frequencies to facilitate filtering and amplifying those signals. The two signals are then mixed in a detector to produce an output signal that is representative of the phase and amplitude change caused by the reflection of the signal at the probe exposed to the fluid. The detector may be a dual phase detector that provides two such output signals that are in phase quadrature. A phase shifter may be provided for selectively changing the phase of the reference signal to improve the sensitivity of at least one of the output signals for more accurate readings and/or for calibration purposes. The two outputs that are in quadrature with respect to each other may be simultaneously monitored to account for drift errors. The output signals are digitized and provided to a computer at a sample rate which may be very high. The computer is operable to identify the fluid based on its complex permittivity as may be useful for identifying the flow rates, determining the fluid mixture ratio, detecting impurities in the fluid, and so forth. Novelty is believed to reside in the use of the real part of complex permittivity to measure small difference in permittivity of the fluid.

Effect of cAMP signaling on expression of glucocorticoid receptor, Bim and Bad in glucocorticoid-sensitive and resistant leukemic and multiple myeloma cells.

PubMed

Dong, Hongli; Carlton, Michael E; Lerner, Adam; Epstein, Paul M

2015-01-01

Stimulation of cAMP signaling induces apoptosis in glucocorticoid-sensitive and resistant CEM leukemic and MM.1 multiple myeloma cell lines, and this effect is enhanced by dexamethasone in both glucocorticoid-sensitive cell types and in glucocorticoid-resistant CEM cells. Expression of the mRNA for the glucocorticoid receptor alpha (GR) promoters 1A3, 1B and 1C, expression of mRNA and protein for GR, and the BH3-only proapoptotic proteins, Bim and Bad, and the phosphorylation state of Bad were examined following stimulation of the cAMP and glucocorticoid signaling pathways. Expression levels of GR promoters were increased by cAMP and glucocorticoid signaling, but GR protein expression was little changed in CEM and decreased in MM.1 cells. Stimulation of these two signaling pathways induced Bim in CEM cells, induced Bad in MM.1 cells, and activated Bad, as indicated by its dephosphorylation on ser112, in both cell types. This study shows that leukemic and multiple myeloma cells, including those resistant to glucocorticoids, can be induced to undergo apoptosis by stimulating the cAMP signaling pathway, with enhancement by glucocorticoids, and the mechanism by which this occurs may be related to changes in Bim and Bad expression, and in all cases, to activation of Bad.

Visual consciousness and bodily self-consciousness.

PubMed

Faivre, Nathan; Salomon, Roy; Blanke, Olaf

2015-02-01

In recent years, consciousness has become a central topic in cognitive neuroscience. This review focuses on the relation between bodily self-consciousness - the feeling of being a subject in a body - and visual consciousness - the subjective experience associated with the perception of visual signals. Findings from clinical and experimental work have shown that bodily self-consciousness depends on specific brain networks and is related to the integration of signals from multiple sensory modalities including vision. In addition, recent experiments have shown that visual consciousness is shaped by the body, including vestibular, tactile, proprioceptive, and motor signals. Several lines of evidence suggest reciprocal relationships between vision and bodily signals, indicating that a comprehensive understanding of visual and bodily self-consciousness requires studying them in unison.

Network-Assisted Investigation of Combined Causal Signals from Genome-Wide Association Studies in Schizophrenia

PubMed Central

Jia, Peilin; Wang, Lily; Fanous, Ayman H.; Pato, Carlos N.; Edwards, Todd L.; Zhao, Zhongming

2012-01-01

With the recent success of genome-wide association studies (GWAS), a wealth of association data has been accomplished for more than 200 complex diseases/traits, proposing a strong demand for data integration and interpretation. A combinatory analysis of multiple GWAS datasets, or an integrative analysis of GWAS data and other high-throughput data, has been particularly promising. In this study, we proposed an integrative analysis framework of multiple GWAS datasets by overlaying association signals onto the protein-protein interaction network, and demonstrated it using schizophrenia datasets. Building on a dense module search algorithm, we first searched for significantly enriched subnetworks for schizophrenia in each single GWAS dataset and then implemented a discovery-evaluation strategy to identify module genes with consistent association signals. We validated the module genes in an independent dataset, and also examined them through meta-analysis of the related SNPs using multiple GWAS datasets. As a result, we identified 205 module genes with a joint effect significantly associated with schizophrenia; these module genes included a number of well-studied candidate genes such as DISC1, GNA12, GNA13, GNAI1, GPR17, and GRIN2B. Further functional analysis suggested these genes are involved in neuronal related processes. Additionally, meta-analysis found that 18 SNPs in 9 module genes had P meta<1×10−4, including the gene HLA-DQA1 located in the MHC region on chromosome 6, which was reported in previous studies using the largest cohort of schizophrenia patients to date. These results demonstrated our bi-directional network-based strategy is efficient for identifying disease-associated genes with modest signals in GWAS datasets. This approach can be applied to any other complex diseases/traits where multiple GWAS datasets are available. PMID:22792057

Hedgehog Signaling in Pancreatic Fibrosis and Cancer

PubMed Central

Bai, Yongyu; Bai, Yongheng; Dong, Jiaojiao; Li, Qiang; Jin, Yuepeng; Chen, Bicheng; Zhou, Mengtao

2016-01-01

Abstract The hedgehog signaling pathway was first discovered in the 1980s. It is a stem cell-related pathway that plays a crucial role in embryonic development, tissue regeneration, and organogenesis. Aberrant activation of hedgehog signaling leads to pathological consequences, including a variety of human tumors such as pancreatic cancer. Multiple lines of evidence indicate that blockade of this pathway with several small-molecule inhibitors can inhibit the development of pancreatic neoplasm. In addition, activated hedgehog signaling has been reported to be involved in fibrogenesis in many tissues, including the pancreas. Therefore, new therapeutic targets based on hedgehog signaling have attracted a great deal of attention to alleviate pancreatic diseases. In this review, we briefly discuss the recent advances in hedgehog signaling in pancreatic fibrogenesis and carcinogenesis and highlight new insights on their potential relationship with respect to the development of novel targeted therapies. PMID:26962810

Method and apparatus for signal processing in a sensor system for use in spectroscopy

DOEpatents

O'Connor, Paul [Bellport, NY; DeGeronimo, Gianluigi [Nesconset, NY; Grosholz, Joseph [Natrona Heights, PA

2008-05-27

A method for processing pulses arriving randomly in time on at least one channel using multiple peak detectors includes asynchronously selecting a non-busy peak detector (PD) in response to a pulse-generated trigger signal, connecting the channel to the selected PD in response to the trigger signal, and detecting a pulse peak amplitude. Amplitude and time of arrival data are output in first-in first-out (FIFO) sequence. An apparatus includes trigger comparators to generate the trigger signal for the pulse-receiving channel, PDs, a switch for connecting the channel to the selected PD, and logic circuitry which maintains the write pointer. Also included, time-to-amplitude converters (TACs) convert time of arrival to analog voltage and an analog multiplexer provides FIFO output. A multi-element sensor system for spectroscopy includes detector elements, channels, trigger comparators, PDs, a switch, and a logic circuit with asynchronous write pointer. The system includes TACs, a multiplexer and analog-to-digital converter.

Medical Signal-Conditioning and Data-Interface System

NASA Technical Reports Server (NTRS)

Braun, Jeffrey; Jacobus, charles; Booth, Scott; Suarez, Michael; Smith, Derek; Hartnagle, Jeffrey; LePrell, Glenn

2006-01-01

A general-purpose portable, wearable electronic signal-conditioning and data-interface system is being developed for medical applications. The system can acquire multiple physiological signals (e.g., electrocardiographic, electroencephalographic, and electromyographic signals) from sensors on the wearer s body, digitize those signals that are received in analog form, preprocess the resulting data, and transmit the data to one or more remote location(s) via a radiocommunication link and/or the Internet. The system includes a computer running data-object-oriented software that can be programmed to configure the system to accept almost any analog or digital input signals from medical devices. The computing hardware and software implement a general-purpose data-routing-and-encapsulation architecture that supports tagging of input data and routing the data in a standardized way through the Internet and other modern packet-switching networks to one or more computer(s) for review by physicians. The architecture supports multiple-site buffering of data for redundancy and reliability, and supports both real-time and slower-than-real-time collection, routing, and viewing of signal data. Routing and viewing stations support insertion of automated analysis routines to aid in encoding, analysis, viewing, and diagnosis.

Evidence for speckle effects on pulsed CO2 lidar signal returns from remote targets

NASA Technical Reports Server (NTRS)

Menzies, R. T.; Kavaya, M. J.; Flamant, P. H.

1984-01-01

A pulsed CO2 lidar was used to study statistical properties of signal returns from various rough surfaces at distances near 2 km. These included natural in situ topographic materials as well as man-made hard targets. Three lidar configurations were used: heterodyne detection with single temporal mode transmitter pulses, and direct detection with single and multiple temporal mode pulses. The significant differences in signal return statistics, due largely to speckle effects, are discussed.

Real-time spatio-temporal coherence estimation for autonomous mode identification and invariance tracking

NASA Technical Reports Server (NTRS)

Park, Han G. (Inventor); Zak, Michail (Inventor); James, Mark L. (Inventor); Mackey, Ryan M. E. (Inventor)

2003-01-01

A general method of anomaly detection from time-correlated sensor data is disclosed. Multiple time-correlated signals are received. Their cross-signal behavior is compared against a fixed library of invariants. The library is constructed during a training process, which is itself data-driven using the same time-correlated signals. The method is applicable to a broad class of problems and is designed to respond to any departure from normal operation, including faults or events that lie outside the training envelope.

Multisensor speech input

NASA Astrophysics Data System (ADS)

Viswanathan, V. R.; Karnofsky, K. F.; Stevens, K. N.; Alakel, M. N.

1983-12-01

The use of multiple sensors to transduce speech was investigated. A data base of speech and noise was collected from a number of transducers located on and around the head of the speaker. The transducers included pressure, first order gradient, second order gradient microphones and an accelerometer. The effort analyzed this data and evaluated the performance of a multiple sensor configuration. The conclusion was: multiple transducer configurations can provide a signal containing more useable speech information than that provided by a microphone.

Multi-channel spatialization systems for audio signals

NASA Technical Reports Server (NTRS)

Begault, Durand R. (Inventor)

1993-01-01

Synthetic head related transfer functions (HRTF's) for imposing reprogrammable spatial cues to a plurality of audio input signals included, for example, in multiple narrow-band audio communications signals received simultaneously are generated and stored in interchangeable programmable read only memories (PROM's) which store both head related transfer function impulse response data and source positional information for a plurality of desired virtual source locations. The analog inputs of the audio signals are filtered and converted to digital signals from which synthetic head related transfer functions are generated in the form of linear phase finite impulse response filters. The outputs of the impulse response filters are subsequently reconverted to analog signals, filtered, mixed, and fed to a pair of headphones.

Multi-channel spatialization system for audio signals

NASA Technical Reports Server (NTRS)

Begault, Durand R. (Inventor)

1995-01-01

Synthetic head related transfer functions (HRTF's) for imposing reprogramable spatial cues to a plurality of audio input signals included, for example, in multiple narrow-band audio communications signals received simultaneously are generated and stored in interchangeable programmable read only memories (PROM's) which store both head related transfer function impulse response data and source positional information for a plurality of desired virtual source locations. The analog inputs of the audio signals are filtered and converted to digital signals from which synthetic head related transfer functions are generated in the form of linear phase finite impulse response filters. The outputs of the impulse response filters are subsequently reconverted to analog signals, filtered, mixed and fed to a pair of headphones.

Power spectrum scale invariance as a neural marker of cocaine misuse and altered cognitive control.

PubMed

Ide, Jaime S; Hu, Sien; Zhang, Sheng; Mujica-Parodi, Lilianne R; Li, Chiang-Shan R

2016-01-01

Magnetic resonance imaging (MRI) has highlighted the effects of chronic cocaine exposure on cerebral structures and functions, and implicated the prefrontal cortices in deficits of cognitive control. Recent investigations suggest power spectrum scale invariance (PSSI) of cerebral blood oxygenation level dependent (BOLD) signals as a neural marker of cerebral activity. We examined here how PSSI is altered in association with cocaine misuse and impaired cognitive control. Eighty-eight healthy (HC) and seventy-five age and gender matched cocaine dependent (CD) adults participated in functional MRI of a stop signal task (SST). BOLD images were preprocessed using standard procedures in SPM, including detrending, band-pass filtering (0.01-0.25 Hz), and correction for head motions. Voxel-wise PSSI measures were estimated by a linear fit of the power spectrum with a log-log scale. In group analyses, we examined differences in PSSI between HC and CD, and its association with clinical and behavioral variables using a multiple regression. A critical component of cognitive control is post-signal behavioral adjustment, which is compromised in cocaine dependence. Therefore, we examined the PSSI changes in association with post-signal slowing (PSS) in the SST. Compared to HC, CD showed decreased PSS and PSSI in multiple frontoparietal regions. PSSI was positively correlated with PSS in HC in multiple regions, including the left inferior frontal gyrus (IFG) and right supramarginal gyrus (SMG), which showed reduced PSSI in CD. These findings suggest disrupted connectivity dynamics in the fronto-parietal areas in association with post-signal behavioral adjustment in cocaine addicts. These new findings support PSSI as a neural marker of impaired cognitive control in cocaine addiction.

Chronic Cigarette Smoke Mediated Global Changes in Lung Mucoepidermoid Cells: A Phosphoproteomic Analysis.

PubMed

Solanki, Hitendra S; Advani, Jayshree; Khan, Aafaque Ahmad; Radhakrishnan, Aneesha; Sahasrabuddhe, Nandini A; Pinto, Sneha M; Chang, Xiaofei; Prasad, Thottethodi Subrahmanya Keshava; Mathur, Premendu Prakash; Sidransky, David; Gowda, Harsha; Chatterjee, Aditi

2017-08-01

Proteomics analysis of chronic cigarette smoke exposure is a rapidly emerging postgenomics research field. While smoking is a major cause of lung cancer, functional studies using proteomics approaches could enrich our mechanistic understanding of the elusive lung cancer global molecular signaling and cigarette smoke relationship. We report in this study on a stable isotope labeling by amino acids in cell culture-based quantitative phosphoproteomic analysis of a human lung mucoepidermoid carcinoma cell line, H292 cells, chronically exposed to cigarette smoke. Using high resolution Orbitrap Velos mass spectrometer, we identified the hyperphosphorylation of 493 sites, which corresponds to 341 proteins and 195 hypophosphorylated sites, mapping to 142 proteins upon smoke exposure (2.0-fold change). We report differential phosphorylation of multiple kinases, including PAK6, EPHA4, LYN, mitogen-activated protein kinase, and phosphatases, including TMEM55B, PTPN14, TIGAR, among others, in response to chronic cigarette smoke exposure. Bioinformatics analysis revealed that the molecules differentially phosphorylated upon chronic exposure of cigarette smoke are associated with PI3K/AKT/mTOR and CDC42-PAK signaling pathways. These signaling networks are involved in multiple cellular processes, including cell polarity, cytoskeletal remodeling, cellular migration, protein synthesis, autophagy, and apoptosis. The present study contributes to emerging proteomics insights on cigarette smoke mediated global signaling in lung cells, which in turn may aid in development of precision medicine therapeutics and postgenomics biomarkers.

Molecular mechanism of TGF-β signaling pathway in colon carcinogenesis and status of curcumin as chemopreventive strategy.

PubMed

Ramamoorthi, Ganesan; Sivalingam, Nageswaran

2014-08-01

Colon cancer is one of the third most common cancer in man, the second most common cancer in women worldwide, and the second leading cause of mortality in the USA. There are a number of molecular pathways that have been implicated in colon carcinogenesis, including TGF-β/Smad signaling pathway. TGF-β (transforming growth factor-beta) signaling pathway has the potential to regulate various biological processes including cell growth, differentiation, apoptosis, extracellular matrix modeling, and immune response. TGF-β signaling pathway acts as a tumor suppressor, but alterations in TGF-β signaling pathway promotes colon cancer cell growth, migration, invasion, angiogenesis, and metastasis. Here we review the role of TGF-β signaling cascade in colon carcinogenesis and multiple molecular targets of curcumin in colon carcinogenesis. Elucidation of the molecular mechanism of curcumin on TGF-β signaling pathway-induced colon carcinogenesis may ultimately lead to novel and more effective treatments for colon cancer.

High-Performance Anti-Retransmission Deception Jamming Utilizing Range Direction Multiple Input and Multiple Output (MIMO) Synthetic Aperture Radar (SAR).

PubMed

Wang, Ruijia; Chen, Jie; Wang, Xing; Sun, Bing

2017-01-09

Retransmission deception jamming seriously degrades the Synthetic Aperture Radar (SAR) detection efficiency and can mislead SAR image interpretation by forming false targets. In order to suppress retransmission deception jamming, this paper proposes a novel multiple input and multiple output (MIMO) SAR structure range direction MIMO SAR, whose multiple channel antennas are vertical to the azimuth. First, based on the multiple channels of range direction MIMO SAR, the orthogonal frequency division multiplexing (OFDM) linear frequency modulation (LFM) signal was adopted as the transmission signal of each channel, which is defined as a sub-band signal. This sub-band signal corresponds to the transmission channel. Then, all of the sub-band signals are modulated with random initial phases and concurrently transmitted. The signal form is more complex and difficult to intercept. Next, the echoes of the sub-band signal are utilized to synthesize a wide band signal after preprocessing. The proposed method will increase the signal to interference ratio and peak amplitude ratio of the signal to resist retransmission deception jamming. Finally, well-focused SAR imagery is obtained using a conventional imaging method where the retransmission deception jamming strength is degraded and defocused. Simulations demonstrated the effectiveness of the proposed method.

High-Performance Anti-Retransmission Deception Jamming Utilizing Range Direction Multiple Input and Multiple Output (MIMO) Synthetic Aperture Radar (SAR)

PubMed Central

Wang, Ruijia; Chen, Jie; Wang, Xing; Sun, Bing

2017-01-01

Retransmission deception jamming seriously degrades the Synthetic Aperture Radar (SAR) detection efficiency and can mislead SAR image interpretation by forming false targets. In order to suppress retransmission deception jamming, this paper proposes a novel multiple input and multiple output (MIMO) SAR structure range direction MIMO SAR, whose multiple channel antennas are vertical to the azimuth. First, based on the multiple channels of range direction MIMO SAR, the orthogonal frequency division multiplexing (OFDM) linear frequency modulation (LFM) signal was adopted as the transmission signal of each channel, which is defined as a sub-band signal. This sub-band signal corresponds to the transmission channel. Then, all of the sub-band signals are modulated with random initial phases and concurrently transmitted. The signal form is more complex and difficult to intercept. Next, the echoes of the sub-band signal are utilized to synthesize a wide band signal after preprocessing. The proposed method will increase the signal to interference ratio and peak amplitude ratio of the signal to resist retransmission deception jamming. Finally, well-focused SAR imagery is obtained using a conventional imaging method where the retransmission deception jamming strength is degraded and defocused. Simulations demonstrated the effectiveness of the proposed method. PMID:28075367

Illegitimate WNT signaling promotes proliferation of multiple myeloma cells

PubMed Central

Derksen, Patrick W. B.; Tjin, Esther; Meijer, Helen P.; Klok, Melanie D.; Mac Gillavry, Harold D.; van Oers, Marinus H. J.; Lokhorst, Henk M.; Bloem, Andries C.; Clevers, Hans; Nusse, Roel; van der Neut, Ronald; Spaargaren, Marcel; Pals, Steven T.

2004-01-01

The unrestrained growth of tumor cells is generally attributed to mutations in essential growth control genes, but tumor cells are also influenced by signals from the environment. In multiple myeloma (MM), the factors and signals coming from the bone marrow microenvironment are possibly even essential for the growth of the tumor cells. As targets for intervention, these signals may be equally important as mutated oncogenes. Given their oncogenic potential, WNT signals form a class of paracrine growth factors that could act to influence MM cell growth. In this paper, we report that MM cells have hallmarks of active WNT signaling, whereas the cells have not undergone detectable mutations in WNT signaling genes such as adenomatous polyposis coli and β-catenin (CTNNB1). We show that the malignant MM plasma cells overexpress β-catenin, including its N-terminally unphosphorylated form, suggesting active β-catenin/T cell factor-mediated transcription. Further accumulation and nuclear localization of β-catenin, and/or increased cell proliferation, was achieved by stimulation of WNT signaling with either Wnt3a, LiCl, or the constitutively active S33Y mutant of β-catenin. In contrast, by blocking WNT signaling by dominant-negative T cell factor, we can interfere with the growth of MM cells. We therefore suggest that MM cells are dependent on an active WNT signal, which may have important implications for the management of this incurable form of cancer. PMID:15067127

Introduction to Communication Systems

DTIC Science & Technology

2014-01-17

channel modeling in complex baseband using ray tracing, reinforced by a software lab which applies these ideas to simulate link time variations for a...analog acoustic signal is generated (often translated to an analog electrical signal using a microphone). Even when this music is recorded onto a...include line of sight (LOS) and reflected paths. Equation (2.35) immediately tells us how to model multipath channels, in which multiple scat- tered

Imaging synthetic aperture radar

DOEpatents

Burns, Bryan L.; Cordaro, J. Thomas

1997-01-01

A linear-FM SAR imaging radar method and apparatus to produce a real-time image by first arranging the returned signals into a plurality of subaperture arrays, the columns of each subaperture array having samples of dechirped baseband pulses, and further including a processing of each subaperture array to obtain coarse-resolution in azimuth, then fine-resolution in range, and lastly, to combine the processed subapertures to obtain the final fine-resolution in azimuth. Greater efficiency is achieved because both the transmitted signal and a local oscillator signal mixed with the returned signal can be varied on a pulse-to-pulse basis as a function of radar motion. Moreover, a novel circuit can adjust the sampling location and the A/D sample rate of the combined dechirped baseband signal which greatly reduces processing time and hardware. The processing steps include implementing a window function, stabilizing either a central reference point and/or all other points of a subaperture with respect to doppler frequency and/or range as a function of radar motion, sorting and compressing the signals using a standard fourier transforms. The stabilization of each processing part is accomplished with vector multiplication using waveforms generated as a function of radar motion wherein these waveforms may be synthesized in integrated circuits. Stabilization of range migration as a function of doppler frequency by simple vector multiplication is a particularly useful feature of the invention; as is stabilization of azimuth migration by correcting for spatially varying phase errors prior to the application of an autofocus process.

Therapeutic Targeting of Tumor-Derived R-Spondin Attenuates β-Catenin Signaling and Tumorigenesis in Multiple Cancer Types.

PubMed

Chartier, Cecile; Raval, Janak; Axelrod, Fumiko; Bond, Chris; Cain, Jennifer; Dee-Hoskins, Cristina; Ma, Shirley; Fischer, Marcus M; Shah, Jalpa; Wei, Jie; Ji, May; Lam, Andrew; Stroud, Michelle; Yen, Wan-Ching; Yeung, Pete; Cancilla, Belinda; O'Young, Gilbert; Wang, Min; Kapoun, Ann M; Lewicki, John; Hoey, Timothy; Gurney, Austin

2016-02-01

Deregulation of the β-catenin signaling has long been associated with cancer. Intracellular components of this pathway, including axin, APC, and β-catenin, are frequently mutated in a range of human tumors, but the contribution of specific extracellular ligands that promote cancer development through this signaling axis remains unclear. We conducted a reporter-based screen in a panel of human tumors to identify secreted factors that stimulate β-catenin signaling. Through this screen and further molecular characterization, we found that R-spondin (RSPO) proteins collaborate with Wnt proteins to activate β-catenin. RSPO family members were expressed in several human tumors representing multiple malignancies, including ovarian, pancreatic, colon, breast, and lung cancer. We generated specific monoclonal antibody antagonists of RSPO family members and found that anti-RSPO treatment markedly inhibited tumor growth in human patient-derived tumor xenograft models, either as single agents or in combination with chemotherapy. Furthermore, blocking RSPO signaling reduced the tumorigenicity of cancer cells based on serial transplantation studies. Moreover, gene-expression analyses revealed that anti-RSPO treatment in responsive tumors strongly inhibited β-catenin target genes known to be associated with cancer and normal stem cells. Collectively, our results suggest that the RSPO family is an important stimulator of β-catenin activity in many human tumors and highlight a new effective approach for therapeutically modulating this fundamental signaling axis. ©2015 American Association for Cancer Research.

Refinement and application of acoustic impulse technique to study nozzle transmission characteristics

NASA Technical Reports Server (NTRS)

Salikuddin, M.; Brown, W. H.; Ramakrishnan, R.; Tanna, H. K.

1983-01-01

An improved acoustic impulse technique was developed and was used to study the transmission characteristics of duct/nozzle systems. To accomplish the above objective, various problems associated with the existing spark-discharge impulse technique were first studied. These included (1) the nonlinear behavior of high intensity pulses, (2) the contamination of the signal with flow noise, (3) low signal-to-noise ratio at high exhaust velocities, and (4) the inability to control or shape the signal generated by the source, specially when multiple spark points were used as the source. The first step to resolve these problems was the replacement of the spark-discharge source with electroacoustic driver(s). These included (1) synthesizing on acoustic impulse with acoustic driver(s) to control and shape the output signal, (2) time domain signal averaging to remove flow noise from the contaminated signal, (3) signal editing to remove unwanted portions of the time history, (4) spectral averaging, and (5) numerical smoothing. The acoustic power measurement technique was improved by taking multiple induct measurements and by a modal decomposition process to account for the contribution of higher order modes in the power computation. The improved acoustic impulse technique was then validated by comparing the results derived by an impedance tube method. The mechanism of acoustic power loss, that occurs when sound is transmitted through nozzle terminations, was investigated. Finally, the refined impulse technique was applied to obtain more accurate results for the acoustic transmission characteristics of a conical nozzle and a multi-lobe multi-tube supressor nozzle.

Automated Method of Frequency Determination in Software Metric Data Through the Use of the Multiple Signal Classification (MUSIC) Algorithm

DTIC Science & Technology

1998-06-26

METHOD OF FREQUENCY DETERMINATION 4 IN SOFTWARE METRIC DATA THROUGH THE USE OF THE 5 MULTIPLE SIGNAL CLASSIFICATION ( MUSIC ) ALGORITHM 6 7 STATEMENT OF...graph showing the estimated power spectral 12 density (PSD) generated by the multiple signal classification 13 ( MUSIC ) algorithm from the data set used...implemented in this module; however, it is preferred to use 1 the Multiple Signal Classification ( MUSIC ) algorithm. The MUSIC 2 algorithm is

XML Encoding of Features Describing Rule-Based Modeling of Reaction Networks with Multi-Component Molecular Complexes

PubMed Central

Blinov, Michael L.; Moraru, Ion I.

2011-01-01

Multi-state molecules and multi-component complexes are commonly involved in cellular signaling. Accounting for molecules that have multiple potential states, such as a protein that may be phosphorylated on multiple residues, and molecules that combine to form heterogeneous complexes located among multiple compartments, generates an effect of combinatorial complexity. Models involving relatively few signaling molecules can include thousands of distinct chemical species. Several software tools (StochSim, BioNetGen) are already available to deal with combinatorial complexity. Such tools need information standards if models are to be shared, jointly evaluated and developed. Here we discuss XML conventions that can be adopted for modeling biochemical reaction networks described by user-specified reaction rules. These could form a basis for possible future extensions of the Systems Biology Markup Language (SBML). PMID:21464833

Cancer stem cells and differentiation therapy.

PubMed

Jin, Xiong; Jin, Xun; Kim, Hyunggee

2017-10-01

Cancer stem cells can generate tumors from only a small number of cells, whereas differentiated cancer cells cannot. The prominent feature of cancer stem cells is its ability to self-renew and differentiate into multiple types of cancer cells. Cancer stem cells have several distinct tumorigenic abilities, including stem cell signal transduction, tumorigenicity, metastasis, and resistance to anticancer drugs, which are regulated by genetic or epigenetic changes. Like normal adult stem cells involved in various developmental processes and tissue homeostasis, cancer stem cells maintain their self-renewal capacity by activating multiple stem cell signaling pathways and inhibiting differentiation signaling pathways during cancer initiation and progression. Recently, many studies have focused on targeting cancer stem cells to eradicate malignancies by regulating stem cell signaling pathways, and products of some of these strategies are in preclinical and clinical trials. In this review, we describe the crucial features of cancer stem cells related to tumor relapse and drug resistance, as well as the new therapeutic strategy to target cancer stem cells named "differentiation therapy."

Coactivation of response initiation processes with redundant signals.

PubMed

Maslovat, Dana; Hajj, Joëlle; Carlsen, Anthony N

2018-05-14

During reaction time (RT) tasks, participants respond faster to multiple stimuli from different modalities as compared to a single stimulus, a phenomenon known as the redundant signal effect (RSE). Explanations for this effect typically include coactivation arising from the multiple stimuli, which results in enhanced processing of one or more response production stages. The current study compared empirical RT data with the predictions of a model in which initiation-related activation arising from each stimulus is additive. Participants performed a simple wrist extension RT task following either a visual go-signal, an auditory go-signal, or both stimuli with the auditory stimulus delayed between 0 and 125 ms relative to the visual stimulus. Results showed statistical equivalence between the predictions of an additive initiation model and the observed RT data, providing novel evidence that the RSE can be explained via a coactivation of initiation-related processes. It is speculated that activation summation occurs at the thalamus, leading to the observed facilitation of response initiation. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of the 10-11 July 2015 two-stage sequence of multiple emplacements of pyroclastic density currents at Volcán de Colima, México: Insight from associated seismic signals

NASA Astrophysics Data System (ADS)

Zobin, Vyacheslav M.

2018-02-01

The 10-11 July 2015 partial collapses of the lava dome in the crater of Volcán de Colima, México, were accompanied by a sequence of two-stage multiple PDCs, separated by a 15-h interval, with a total bulk volume of 14.2 × 106 m3 of fragmentary material and runout distances reaching 9.1 and 10.3 km, respectively (Reyes-Dávila et al., 2016). Broad-band seismic signals, associated with the PDCs and recorded at seismic station EZ5 installed at a distance of 4 km from the crater, were used for analysis of the 20-h eruption process. This process included two stages of the multiple PDCs emplacements, two one-hour periods of preliminary events to each of the stages, and the inter-stage period. Analysis of seismic signals allowed us to identify the types of volcanic events composing this eruption episode and estimate their quantitative characteristics and spectral parameters of generated seismic signals. It was shown that the seismic signals produced by PDCs emplacements, recorded during the two stages, were characterized by different characteristics. The second stage PDCs had radiated greater seismic energy than the PDCs emplaced during the first stage. Spectral analysis of the seismic signals, produced by PDCs, indicates a clearly separation in frequency content at 1.95 Hz between the higher-frequency events of the first stage and the lower-frequency events of the second stage of the PDCs emplacements. The obtained difference in the spectral contents of the seismic signals, produced by the movement of two multiple PDCs, may be supposed as a consequence of the proposed relative difference in the volumes of the PDCs of two multiple sequences due to a difference in the level of radiated seismic energy and a change in bottom conditions of the ravines during their passing along the ravines. Results of seismic study were used in discussion of the nature of the two-stage eruptive process.

Sparse representation of whole-brain fMRI signals for identification of functional networks.

PubMed

Lv, Jinglei; Jiang, Xi; Li, Xiang; Zhu, Dajiang; Chen, Hanbo; Zhang, Tuo; Zhang, Shu; Hu, Xintao; Han, Junwei; Huang, Heng; Zhang, Jing; Guo, Lei; Liu, Tianming

2015-02-01

There have been several recent studies that used sparse representation for fMRI signal analysis and activation detection based on the assumption that each voxel's fMRI signal is linearly composed of sparse components. Previous studies have employed sparse coding to model functional networks in various modalities and scales. These prior contributions inspired the exploration of whether/how sparse representation can be used to identify functional networks in a voxel-wise way and on the whole brain scale. This paper presents a novel, alternative methodology of identifying multiple functional networks via sparse representation of whole-brain task-based fMRI signals. Our basic idea is that all fMRI signals within the whole brain of one subject are aggregated into a big data matrix, which is then factorized into an over-complete dictionary basis matrix and a reference weight matrix via an effective online dictionary learning algorithm. Our extensive experimental results have shown that this novel methodology can uncover multiple functional networks that can be well characterized and interpreted in spatial, temporal and frequency domains based on current brain science knowledge. Importantly, these well-characterized functional network components are quite reproducible in different brains. In general, our methods offer a novel, effective and unified solution to multiple fMRI data analysis tasks including activation detection, de-activation detection, and functional network identification. Copyright © 2014 Elsevier B.V. All rights reserved.

Seismic data fusion anomaly detection

NASA Astrophysics Data System (ADS)

Harrity, Kyle; Blasch, Erik; Alford, Mark; Ezekiel, Soundararajan; Ferris, David

2014-06-01

Detecting anomalies in non-stationary signals has valuable applications in many fields including medicine and meteorology. These include uses such as identifying possible heart conditions from an Electrocardiography (ECG) signals or predicting earthquakes via seismographic data. Over the many choices of anomaly detection algorithms, it is important to compare possible methods. In this paper, we examine and compare two approaches to anomaly detection and see how data fusion methods may improve performance. The first approach involves using an artificial neural network (ANN) to detect anomalies in a wavelet de-noised signal. The other method uses a perspective neural network (PNN) to analyze an arbitrary number of "perspectives" or transformations of the observed signal for anomalies. Possible perspectives may include wavelet de-noising, Fourier transform, peak-filtering, etc.. In order to evaluate these techniques via signal fusion metrics, we must apply signal preprocessing techniques such as de-noising methods to the original signal and then use a neural network to find anomalies in the generated signal. From this secondary result it is possible to use data fusion techniques that can be evaluated via existing data fusion metrics for single and multiple perspectives. The result will show which anomaly detection method, according to the metrics, is better suited overall for anomaly detection applications. The method used in this study could be applied to compare other signal processing algorithms.

Detecting signals of drug-drug interactions in a spontaneous reports database.

PubMed

Thakrar, Bharat T; Grundschober, Sabine Borel; Doessegger, Lucette

2007-10-01

The spontaneous reports database is widely used for detecting signals of ADRs. We have extended the methodology to include the detection of signals of ADRs that are associated with drug-drug interactions (DDI). In particular, we have investigated two different statistical assumptions for detecting signals of DDI. Using the FDA's spontaneous reports database, we investigated two models, a multiplicative and an additive model, to detect signals of DDI. We applied the models to four known DDIs (methotrexate-diclofenac and bone marrow depression, simvastatin-ciclosporin and myopathy, ketoconazole-terfenadine and torsades de pointes, and cisapride-erythromycin and torsades de pointes) and to four drug-event combinations where there is currently no evidence of a DDI (fexofenadine-ketoconazole and torsades de pointes, methotrexade-rofecoxib and bone marrow depression, fluvastatin-ciclosporin and myopathy, and cisapride-azithromycine and torsade de pointes) and estimated the measure of interaction on the two scales. The additive model correctly identified all four known DDIs by giving a statistically significant (P < 0.05) positive measure of interaction. The multiplicative model identified the first two of the known DDIs as having a statistically significant or borderline significant (P < 0.1) positive measure of interaction term, gave a nonsignificant positive trend for the third interaction (P = 0.27), and a negative trend for the last interaction. Both models correctly identified the four known non interactions by estimating a negative measure of interaction. The spontaneous reports database is a valuable resource for detecting signals of DDIs. In particular, the additive model is more sensitive in detecting such signals. The multiplicative model may further help qualify the strength of the signal detected by the additive model.

Detecting signals of drug–drug interactions in a spontaneous reports database

PubMed Central

Thakrar, Bharat T; Grundschober, Sabine Borel; Doessegger, Lucette

2007-01-01

Aims The spontaneous reports database is widely used for detecting signals of ADRs. We have extended the methodology to include the detection of signals of ADRs that are associated with drug–drug interactions (DDI). In particular, we have investigated two different statistical assumptions for detecting signals of DDI. Methods Using the FDA's spontaneous reports database, we investigated two models, a multiplicative and an additive model, to detect signals of DDI. We applied the models to four known DDIs (methotrexate-diclofenac and bone marrow depression, simvastatin-ciclosporin and myopathy, ketoconazole-terfenadine and torsades de pointes, and cisapride-erythromycin and torsades de pointes) and to four drug-event combinations where there is currently no evidence of a DDI (fexofenadine-ketoconazole and torsades de pointes, methotrexade-rofecoxib and bone marrow depression, fluvastatin-ciclosporin and myopathy, and cisapride-azithromycine and torsade de pointes) and estimated the measure of interaction on the two scales. Results The additive model correctly identified all four known DDIs by giving a statistically significant (P< 0.05) positive measure of interaction. The multiplicative model identified the first two of the known DDIs as having a statistically significant or borderline significant (P< 0.1) positive measure of interaction term, gave a nonsignificant positive trend for the third interaction (P= 0.27), and a negative trend for the last interaction. Both models correctly identified the four known non interactions by estimating a negative measure of interaction. Conclusions The spontaneous reports database is a valuable resource for detecting signals of DDIs. In particular, the additive model is more sensitive in detecting such signals. The multiplicative model may further help qualify the strength of the signal detected by the additive model. PMID:17506784

Phase discriminating capacitive array sensor system

NASA Technical Reports Server (NTRS)

Vranish, John M. (Inventor); Rahim, Wadi (Inventor)

1993-01-01

A phase discriminating capacitive sensor array system which provides multiple sensor elements which are maintained at a phase and amplitude based on a frequency reference provided by a single frequency stabilized oscillator. Sensor signals provided by the multiple sensor elements are controlled by multiple phase control units, which correspond to the multiple sensor elements, to adjust the sensor signals from the multiple sensor elements based on the frequency reference. The adjustment made to the sensor signals is indicated by output signals which indicate the proximity of the object. The output signals may also indicate the closing speed of the object based on the rate of change of the adjustment made, and the edges of the object based on a sudden decrease in the adjustment made.

Detection of Multiple Stationary Humans Using UWB MIMO Radar.

PubMed

Liang, Fulai; Qi, Fugui; An, Qiang; Lv, Hao; Chen, Fuming; Li, Zhao; Wang, Jianqi

2016-11-16

Remarkable progress has been achieved in the detection of single stationary human. However, restricted by the mutual interference of multiple humans (e.g., strong sidelobes of the torsos and the shadow effect), detection and localization of the multiple stationary humans remains a huge challenge. In this paper, ultra-wideband (UWB) multiple-input and multiple-output (MIMO) radar is exploited to improve the detection performance of multiple stationary humans for its multiple sight angles and high-resolution two-dimensional imaging capacity. A signal model of the vital sign considering both bi-static angles and attitude angle of the human body is firstly developed, and then a novel detection method is proposed to detect and localize multiple stationary humans. In this method, preprocessing is firstly implemented to improve the signal-to-noise ratio (SNR) of the vital signs, and then a vital-sign-enhanced imaging algorithm is presented to suppress the environmental clutters and mutual affection of multiple humans. Finally, an automatic detection algorithm including constant false alarm rate (CFAR), morphological filtering and clustering is implemented to improve the detection performance of weak human targets affected by heavy clutters and shadow effect. The simulation and experimental results show that the proposed method can get a high-quality image of multiple humans and we can use it to discriminate and localize multiple adjacent human targets behind brick walls.

Detection of Multiple Stationary Humans Using UWB MIMO Radar

PubMed Central

Liang, Fulai; Qi, Fugui; An, Qiang; Lv, Hao; Chen, Fuming; Li, Zhao; Wang, Jianqi

2016-01-01

Remarkable progress has been achieved in the detection of single stationary human. However, restricted by the mutual interference of multiple humans (e.g., strong sidelobes of the torsos and the shadow effect), detection and localization of the multiple stationary humans remains a huge challenge. In this paper, ultra-wideband (UWB) multiple-input and multiple-output (MIMO) radar is exploited to improve the detection performance of multiple stationary humans for its multiple sight angles and high-resolution two-dimensional imaging capacity. A signal model of the vital sign considering both bi-static angles and attitude angle of the human body is firstly developed, and then a novel detection method is proposed to detect and localize multiple stationary humans. In this method, preprocessing is firstly implemented to improve the signal-to-noise ratio (SNR) of the vital signs, and then a vital-sign-enhanced imaging algorithm is presented to suppress the environmental clutters and mutual affection of multiple humans. Finally, an automatic detection algorithm including constant false alarm rate (CFAR), morphological filtering and clustering is implemented to improve the detection performance of weak human targets affected by heavy clutters and shadow effect. The simulation and experimental results show that the proposed method can get a high-quality image of multiple humans and we can use it to discriminate and localize multiple adjacent human targets behind brick walls. PMID:27854356

Faster processing of multiple spatially-heterodyned direct to digital holograms

DOEpatents

Hanson, Gregory R.; Bingham, Philip R.

2006-10-03

Systems and methods are described for faster processing of multiple spatially-heterodyned direct to digital holograms. A method includes of obtaining multiple spatially-heterodyned holograms, includes: digitally recording a first spatially-heterodyned hologram including spatial heterodyne fringes for Fourier analysis; digitally recording a second spatially-heterodyned hologram including spatial heterodyne fringes for Fourier analysis; Fourier analyzing the recorded first spatially-heterodyned hologram by shifting a first original origin of the recorded first spatially-heterodyned hologram including spatial heterodyne fringes in Fourier space to sit on top of a spatial-heterodyne carrier frequency defined as a first angle between a first reference beam and a first, object beam; applying a first digital filter to cut off signals around the first original origin and performing an inverse Fourier transform on the result; Fourier analyzing the recorded second spatially-heterodyned hologram by shifting a second original origin of the recorded second spatially-heterodyned hologram including spatial heterodyne fringes in Fourier space to sit on top of a spatial-heterodyne carrier frequency defined as a second angle between a second reference beam and a second object beam; and applying a second digital filter to cut off signals around the second original origin and performing an inverse Fourier transform on the result, wherein digitally recording the first spatially-heterodyned hologram is completed before digitally recording the second spatially-heterodyned hologram and a single digital image includes both the first spatially-heterodyned hologram and the second spatially-heterodyned hologram.

Faster processing of multiple spatially-heterodyned direct to digital holograms

DOEpatents

Hanson, Gregory R [Clinton, TN; Bingham, Philip R [Knoxville, TN

2008-09-09

Systems and methods are described for faster processing of multiple spatially-heterodyned direct to digital holograms. A method includes of obtaining multiple spatially-heterodyned holograms, includes: digitally recording a first spatially-heterodyned hologram including spatial heterodyne fringes for Fourier analysis; digitally recording a second spatially-heterodyned hologram including spatial heterodyne fringes for Fourier analysis; Fourier analyzing the recorded first spatially-heterodyned hologram by shifting a first original origin of the recorded first spatially-heterodyned hologram including spatial heterodyne fringes in Fourier space to sit on top of a spatial-heterodyne carrier frequency defined as a first angle between a first reference beam and a first object beam; applying a first digital filter to cut off signals around the first original origin and performing an inverse Fourier transform on the result; Fourier analyzing the recorded second spatially-heterodyned hologram by shifting a second original origin of the recorded second spatially-heterodyned hologram including spatial heterodyne fringes in Fourier space to sit on top of a spatial-heterodyne carrier frequency defined as a second angle between a second reference beam and a second object beam; and applying a second digital filter to cut off signals around the second original origin and performing an inverse Fourier transform on the result, wherein digitally recording the first spatially-heterodyned hologram is completed before digitally recording the second spatially-heterodyned hologram and a single digital image includes both the first spatially-heterodyned hologram and the second spatially-heterodyned hologram.

Hierarchical Robot Control System and Method for Controlling Select Degrees of Freedom of an Object Using Multiple Manipulators

NASA Technical Reports Server (NTRS)

Platt, Robert (Inventor); Wampler, II, Charles W. (Inventor); Abdallah, Muhammad E. (Inventor)

2013-01-01

A robotic system includes a robot having manipulators for grasping an object using one of a plurality of grasp types during a primary task, and a controller. The controller controls the manipulators during the primary task using a multiple-task control hierarchy, and automatically parameterizes the internal forces of the system for each grasp type in response to an input signal. The primary task is defined at an object-level of control, e.g., using a closed-chain transformation, such that only select degrees of freedom are commanded for the object. A control system for the robotic system has a host machine and algorithm for controlling the manipulators using the above hierarchy. A method for controlling the system includes receiving and processing the input signal using the host machine, including defining the primary task at the object-level of control, e.g., using a closed-chain definition, and parameterizing the internal forces for each of grasp type.

Multimodal signalling in estrildid finches: song, dance and colour are associated with different ecological and life-history traits.

PubMed

Gomes, A C R; Funghi, C; Soma, M; Sorenson, M D; Cardoso, G C

2017-07-01

Sexual traits (e.g. visual ornaments, acoustic signals, courtship behaviour) are often displayed together as multimodal signals. Some hypotheses predict joint evolution of different sexual signals (e.g. to increase the efficiency of communication) or that different signals trade off with each other (e.g. due to limited resources). Alternatively, multiple signals may evolve independently for different functions, or to communicate different information (multiple message hypothesis). We evaluated these hypotheses with a comparative study in the family Estrildidae, one of the largest songbird radiations, and one that includes many model species for research in sexual selection and communication. We found little evidence for either joint evolution or trade-offs between song and colour ornamentation. Some negative correlations between dance repertoire and song traits may suggest a functional compromise, but generally courtship dance also evolved independently from other signals. Instead of correlated evolution, we found that song, dance and colour are each related to different socio-ecological traits. Song complexity evolved together with ecological generalism, song performance with investment in reproduction, dance with commonness and habitat type, whereas colour ornamentation was shown previously to correlate mostly with gregariousness. We conclude that multimodal signals evolve in response to various socio-ecological traits, suggesting the accumulation of distinct signalling functions. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

The Hippo Pathway: Immunity and Cancer.

PubMed

Taha, Zaid; J Janse van Rensburg, Helena; Yang, Xiaolong

2018-03-28

Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats. We further discuss how Hippo signaling functions as part of an immune response. Finally, we review how immune cell-intrinsic Hippo signaling modulates the development/function of leukocytes and propose directions for future work.

Integrated analysis of miRNA and mRNA expression data identifies multiple miRNAs regulatory networks for the tumorigenesis of colorectal cancer.

PubMed

Xu, Peng; Wang, Junhua; Sun, Bo; Xiao, Zhongdang

2018-06-15

Investigating the potential biological function of differential changed genes through integrating multiple omics data including miRNA and mRNA expression profiles, is always hot topic. However, how to evaluate the repression effect on target genes integrating miRNA and mRNA expression profiles are not fully solved. In this study, we provide an analyzing method by integrating both miRNAs and mRNAs expression data simultaneously. Difference analysis was adopted based on the repression score, then significantly repressed mRNAs were screened out by DEGseq. Pathway analysis for the significantly repressed mRNAs shows that multiple pathways such as MAPK signaling pathway, TGF-beta signaling pathway and so on, may correlated to the colorectal cancer(CRC). Focusing on the MAPK signaling pathway, a miRNA-mRNA network that centering the cell fate genes was constructed. Finally, the miRNA-mRNAs that potentially important in the CRC carcinogenesis were screened out and scored by impact index. Copyright © 2018 Elsevier B.V. All rights reserved.

Proceedings of the Mobile Satellite System Architectures and Multiple Access Techniques Workshop

NASA Technical Reports Server (NTRS)

Dessouky, Khaled

1989-01-01

The Mobile Satellite System Architectures and Multiple Access Techniques Workshop served as a forum for the debate of system and network architecture issues. Particular emphasis was on those issues relating to the choice of multiple access technique(s) for the Mobile Satellite Service (MSS). These proceedings contain articles that expand upon the 12 presentations given in the workshop. Contrasting views on Frequency Division Multiple Access (FDMA), Code Division Multiple Access (CDMA), and Time Division Multiple Access (TDMA)-based architectures are presented, and system issues relating to signaling, spacecraft design, and network management constraints are addressed. An overview article that summarizes the issues raised in the numerous discussion periods of the workshop is also included.

Non-heuristic automatic techniques for overcoming low signal-to-noise-ratio bias of localization microscopy and multiple signal classification algorithm.

PubMed

Agarwal, Krishna; Macháň, Radek; Prasad, Dilip K

2018-03-21

Localization microscopy and multiple signal classification algorithm use temporal stack of image frames of sparse emissions from fluorophores to provide super-resolution images. Localization microscopy localizes emissions in each image independently and later collates the localizations in all the frames, giving same weight to each frame irrespective of its signal-to-noise ratio. This results in a bias towards frames with low signal-to-noise ratio and causes cluttered background in the super-resolved image. User-defined heuristic computational filters are employed to remove a set of localizations in an attempt to overcome this bias. Multiple signal classification performs eigen-decomposition of the entire stack, irrespective of the relative signal-to-noise ratios of the frames, and uses a threshold to classify eigenimages into signal and null subspaces. This results in under-representation of frames with low signal-to-noise ratio in the signal space and over-representation in the null space. Thus, multiple signal classification algorithms is biased against frames with low signal-to-noise ratio resulting into suppression of the corresponding fluorophores. This paper presents techniques to automatically debias localization microscopy and multiple signal classification algorithm of these biases without compromising their resolution and without employing heuristics, user-defined criteria. The effect of debiasing is demonstrated through five datasets of invitro and fixed cell samples.

Use of Multiscale Entropy to Facilitate Artifact Detection in Electroencephalographic Signals

PubMed Central

Mariani, Sara; Borges, Ana F. T.; Henriques, Teresa; Goldberger, Ary L.; Costa, Madalena D.

2016-01-01

Electroencephalographic (EEG) signals present a myriad of challenges to analysis, beginning with the detection of artifacts. Prior approaches to noise detection have utilized multiple techniques, including visual methods, independent component analysis and wavelets. However, no single method is broadly accepted, inviting alternative ways to address this problem. Here, we introduce a novel approach based on a statistical physics method, multiscale entropy (MSE) analysis, which quantifies the complexity of a signal. We postulate that noise corrupted EEG signals have lower information content, and, therefore, reduced complexity compared with their noise free counterparts. We test the new method on an open-access database of EEG signals with and without added artifacts due to electrode motion. PMID:26738116

Variable Camber Continuous Aerodynamic Control Surfaces and Methods for Active Wing Shaping Control

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T. (Inventor)

2016-01-01

An aerodynamic control apparatus for an air vehicle improves various aerodynamic performance metrics by employing multiple spanwise flap segments that jointly form a continuous or a piecewise continuous trailing edge to minimize drag induced by lift or vortices. At least one of the multiple spanwise flap segments includes a variable camber flap subsystem having multiple chordwise flap segments that may be independently actuated. Some embodiments also employ a continuous leading edge slat system that includes multiple spanwise slat segments, each of which has one or more chordwise slat segment. A method and an apparatus for implementing active control of a wing shape are also described and include the determination of desired lift distribution to determine the improved aerodynamic deflection of the wings. Flap deflections are determined and control signals are generated to actively control the wing shape to approximate the desired deflection.

Hybrid wireless-over-fiber transmission system based on multiple injection-locked FP LDs.

PubMed

Li, Chung-Yi; Lu, Hai-Han; Chu, Chien-An; Ying, Cheng-Ling; Lu, Ting-Chien; Peng, Peng-Chun

2015-07-27

A hybrid wireless-over-fiber (WoF) transmission system based on multiple injection-locked Fabry-Perot laser diodes (FP LDs) is proposed and experimentally demonstrated. Unlike the traditional hybrid WoF transmission systems that require multiple distributed feedback (DFB) LDs to support different kinds of services, the proposed system employs multiple injection-locked FP LDs to provide different kinds of applications. Such a hybrid WoF transmission system delivers downstream intensity-modulated 20-GHz microwave (MW)/60-GHz millimeter-wave (MMW)/550-MHz cable television (CATV) signals and upstream phase-remodulated 20-GHz MW signal. Excellent bit error rate (BER), carrier-to-noise ratio (CNR), composite second-order (CSO), and composite triple-beat (CTB) are observed over a 40-km single-mode fiber (SMF) and a 4-m radio frequency (RF) wireless transport. Such a hybrid WoF transmission system has practical applications for fiber-wireless convergence to provide broadband integrated services, including telecommunication, data communication, and CATV services.

Development of Parallel Architectures for Sensor Array Processing. Volume 1

DTIC Science & Technology

1993-08-01

required for the DOA estimation [ 1-7]. The Multiple Signal Classification ( MUSIC ) [ 1] and the Estimation of Signal Parameters by Rotational...manifold and the estimated subspace. Although MUSIC is a high resolution algorithm, it has several drawbacks including the fact that complete knowledge of...thoroughly, MUSIC algorithm was selected to develop special purpose hardware for real time computation. Summary of the MUSIC algorithm is as follows

Morphological spot counting from stacked images for automated analysis of gene copy numbers by fluorescence in situ hybridization.

PubMed

Grigoryan, Artyom M; Dougherty, Edward R; Kononen, Juha; Bubendorf, Lukas; Hostetter, Galen; Kallioniemi, Olli

2002-01-01

Fluorescence in situ hybridization (FISH) is a molecular diagnostic technique in which a fluorescent labeled probe hybridizes to a target nucleotide sequence of deoxyribose nucleic acid. Upon excitation, each chromosome containing the target sequence produces a fluorescent signal (spot). Because fluorescent spot counting is tedious and often subjective, automated digital algorithms to count spots are desirable. New technology provides a stack of images on multiple focal planes throughout a tissue sample. Multiple-focal-plane imaging helps overcome the biases and imprecision inherent in single-focal-plane methods. This paper proposes an algorithm for global spot counting in stacked three-dimensional slice FISH images without the necessity of nuclei segmentation. It is designed to work in complex backgrounds, when there are agglomerated nuclei, and in the presence of illumination gradients. It is based on the morphological top-hat transform, which locates intensity spikes on irregular backgrounds. After finding signals in the slice images, the algorithm groups these together to form three-dimensional spots. Filters are employed to separate legitimate spots from fluorescent noise. The algorithm is set in a comprehensive toolbox that provides visualization and analytic facilities. It includes simulation software that allows examination of algorithm performance for various image and algorithm parameter settings, including signal size, signal density, and the number of slices.

A regression technique for evaluation and quantification for water quality parameters from remote sensing data

NASA Technical Reports Server (NTRS)

Whitlock, C. H.; Kuo, C. Y.

1979-01-01

The objective of this paper is to define optical physics and/or environmental conditions under which the linear multiple-regression should be applicable. An investigation of the signal-response equations is conducted and the concept is tested by application to actual remote sensing data from a laboratory experiment performed under controlled conditions. Investigation of the signal-response equations shows that the exact solution for a number of optical physics conditions is of the same form as a linearized multiple-regression equation, even if nonlinear contributions from surface reflections, atmospheric constituents, or other water pollutants are included. Limitations on achieving this type of solution are defined.

Multi-Mode, Multi-Antenna Software Defined Radar for Adaptive Tracking and Identification of Targets in Urban Environments

DTIC Science & Technology

2011-10-31

designs with code division multiple access ( CDMA ). Analog chirp filters were used to produce an up-chirp, which is used as a radar waveform, coupled with...signals. A potential shortcoming of CDMA techniques is that the addition of two signals will result in a non-constant amplitude signal which will be...of low-frequency A/ Ds . As an example for a multiple carrier signal all the received signals from the multiple carriers are aliased onto the

Comparison of Signals from Gravitational Wave Detectors with Instantaneous Time-Frequency Maps

NASA Technical Reports Server (NTRS)

Stroeer, A.; Blackburn, L.; Camp, J.

2011-01-01

Gravitational wave astronomy relies on the use of multiple detectors, so that coincident detections may distinguish real signals from instrumental artifacts, and also so that relative timing of signals can provide the sky position of sources. We show that the comparison of instantaneous time-frequency and time-amplitude maps provided by the Hilbert-Huang Transform (HHT) can be used effectively for relative signal timing of common signals, to discriminate between the case of identical coincident signals and random noise coincidences and to provide a classification of signals based on their time-frequency trajectories. The comparison is done with a X(sup 2) goodness-offit method which includes contributions from both the instantaneous amplitude and frequency components of the HHT to match two signals in the time domain. This approach naturally allows the analysis of waveforms with strong frequency modulation.

Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer.

PubMed

Roberts, David D; Kaur, Sukhbir; Isenberg, Jeffrey S

2017-10-20

In contrast to structural elements of the extracellular matrix, matricellular proteins appear transiently during development and injury responses, but their sustained expression can contribute to chronic disease. Through interactions with other matrix components and specific cell surface receptors, matricellular proteins regulate multiple signaling pathways, including those mediated by reactive oxygen and nitrogen species and H 2 S. Dysregulation of matricellular proteins contributes to the pathogenesis of vascular diseases and cancer. Defining the molecular mechanisms and receptors involved is revealing new therapeutic opportunities. Recent Advances: Thrombospondin-1 (TSP1) regulates NO, H 2 S, and superoxide production and signaling in several cell types. The TSP1 receptor CD47 plays a central role in inhibition of NO signaling, but other TSP1 receptors also modulate redox signaling. The matricellular protein CCN1 engages some of the same receptors to regulate redox signaling, and ADAMTS1 regulates NO signaling in Marfan syndrome. In addition to mediating matricellular protein signaling, redox signaling is emerging as an important pathway that controls the expression of several matricellular proteins. Redox signaling remains unexplored for many matricellular proteins. Their interactions with multiple cellular receptors remains an obstacle to defining signaling mechanisms, but improved transgenic models could overcome this barrier. Therapeutics targeting the TSP1 receptor CD47 may have beneficial effects for treating cardiovascular disease and cancer and have recently entered clinical trials. Biomarkers are needed to assess their effects on redox signaling in patients and to evaluate how these contribute to their therapeutic efficacy and potential side effects. Antioxid. Redox Signal. 27, 874-911.

A Global Framework for Monitoring Phenological Responses to Climate Change

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

White, Michael A; Hoffman, Forrest M; Hargrove, William Walter

2005-01-01

Remote sensing of vegetation phenology is an important method with which to monitor terrestrial responses to climate change, but most approaches include signals from multiple forcings, such as mixed phenological signals from multiple biomes, urbanization, political changes, shifts in agricultural practices, and disturbances. Consequently, it is difficult to extract a clear signal from the usually assumed forcing: climate change. Here, using global 8 km 1982 to 1999 Normalized Difference Vegetation Index (NDVI) data and an eight-element monthly climatology, we identified pixels whose wavelet power spectrum was consistently dominated by annual cycles and then created phenologically and climatically self-similar clusters, whichmore » we term phenoregions. We then ranked and screened each phenoregion as a function of landcover homogeneity and consistency, evidence of human impacts, and political diversity. Remaining phenoregions represented areas with a minimized probability of non-climatic forcings and form elemental units for long-term phenological monitoring.« less

Endocannabinoid signalling and the deteriorating brain

PubMed Central

Di Marzo, Vincenzo; Stella, Nephi; Zimmer, Andreas

2015-01-01

Ageing is characterized by the progressive impairment of physiological functions and increased risk of developing debilitating disorders, including chronic inflammation and neurodegenerative diseases. These disorders have common molecular mechanisms that can be targeted therapeutically. In the wake of the approval of the first cannabinoid-based drug for the symptomatic treatment of multiple sclerosis, we examine how endocannabinoid (eCB) signalling controls — and is affected by — normal ageing and neuroinflammatory and neurodegenerative disorders. We propose a conceptual framework linking eCB signalling to the control of the cellular and molecular hallmarks of these processes, and categorize the key components of endocannabinoid signalling that may serve as targets for novel therapeutics. PMID:25524120

MFAM: Multiple Frequency Adaptive Model-Based Indoor Localization Method.

PubMed

Tuta, Jure; Juric, Matjaz B

2018-03-24

This paper presents MFAM (Multiple Frequency Adaptive Model-based localization method), a novel model-based indoor localization method that is capable of using multiple wireless signal frequencies simultaneously. It utilizes indoor architectural model and physical properties of wireless signal propagation through objects and space. The motivation for developing multiple frequency localization method lies in the future Wi-Fi standards (e.g., 802.11ah) and the growing number of various wireless signals present in the buildings (e.g., Wi-Fi, Bluetooth, ZigBee, etc.). Current indoor localization methods mostly rely on a single wireless signal type and often require many devices to achieve the necessary accuracy. MFAM utilizes multiple wireless signal types and improves the localization accuracy over the usage of a single frequency. It continuously monitors signal propagation through space and adapts the model according to the changes indoors. Using multiple signal sources lowers the required number of access points for a specific signal type while utilizing signals, already present in the indoors. Due to the unavailability of the 802.11ah hardware, we have evaluated proposed method with similar signals; we have used 2.4 GHz Wi-Fi and 868 MHz HomeMatic home automation signals. We have performed the evaluation in a modern two-bedroom apartment and measured mean localization error 2.0 to 2.3 m and median error of 2.0 to 2.2 m. Based on our evaluation results, using two different signals improves the localization accuracy by 18% in comparison to 2.4 GHz Wi-Fi-only approach. Additional signals would improve the accuracy even further. We have shown that MFAM provides better accuracy than competing methods, while having several advantages for real-world usage.

MFAM: Multiple Frequency Adaptive Model-Based Indoor Localization Method

PubMed Central

Juric, Matjaz B.

2018-01-01

This paper presents MFAM (Multiple Frequency Adaptive Model-based localization method), a novel model-based indoor localization method that is capable of using multiple wireless signal frequencies simultaneously. It utilizes indoor architectural model and physical properties of wireless signal propagation through objects and space. The motivation for developing multiple frequency localization method lies in the future Wi-Fi standards (e.g., 802.11ah) and the growing number of various wireless signals present in the buildings (e.g., Wi-Fi, Bluetooth, ZigBee, etc.). Current indoor localization methods mostly rely on a single wireless signal type and often require many devices to achieve the necessary accuracy. MFAM utilizes multiple wireless signal types and improves the localization accuracy over the usage of a single frequency. It continuously monitors signal propagation through space and adapts the model according to the changes indoors. Using multiple signal sources lowers the required number of access points for a specific signal type while utilizing signals, already present in the indoors. Due to the unavailability of the 802.11ah hardware, we have evaluated proposed method with similar signals; we have used 2.4 GHz Wi-Fi and 868 MHz HomeMatic home automation signals. We have performed the evaluation in a modern two-bedroom apartment and measured mean localization error 2.0 to 2.3 m and median error of 2.0 to 2.2 m. Based on our evaluation results, using two different signals improves the localization accuracy by 18% in comparison to 2.4 GHz Wi-Fi-only approach. Additional signals would improve the accuracy even further. We have shown that MFAM provides better accuracy than competing methods, while having several advantages for real-world usage. PMID:29587352

System and process for pulsed multiple reaction monitoring

DOEpatents

Belov, Mikhail E

2013-05-17

A new pulsed multiple reaction monitoring process and system are disclosed that uses a pulsed ion injection mode for use in conjunction with triple-quadrupole instruments. The pulsed injection mode approach reduces background ion noise at the detector, increases amplitude of the ion signal, and includes a unity duty cycle that provides a significant sensitivity increase for reliable quantitation of proteins/peptides present at attomole levels in highly complex biological mixtures.

Genetics Home Reference: familial pityriasis rubra pilaris

MedlinePlus

... interacting proteins known as nuclear factor-kappa-B (NF-κB). NF-κB regulates the activity of multiple genes, including ... but it is particularly abundant in the skin. NF-κB signaling appears to play an important role ...

Stochastic sensing through covalent interactions

DOEpatents

Bayley, Hagan; Shin, Seong-Ho; Luchian, Tudor; Cheley, Stephen

2013-03-26

A system and method for stochastic sensing in which the analyte covalently bonds to the sensor element or an adaptor element. If such bonding is irreversible, the bond may be broken by a chemical reagent. The sensor element may be a protein, such as the engineered P.sub.SH type or .alpha.HL protein pore. The analyte may be any reactive analyte, including chemical weapons, environmental toxins and pharmaceuticals. The analyte covalently bonds to the sensor element to produce a detectable signal. Possible signals include change in electrical current, change in force, and change in fluorescence. Detection of the signal allows identification of the analyte and determination of its concentration in a sample solution. Multiple analytes present in the same solution may be detected.

Multiple Signal Classification for Determining Direction of Arrival of Frequency Hopping Spread Spectrum Signals

DTIC Science & Technology

2014-03-27

42 4.2.3 Number of Hops Hs . . . . . . . . . . . . . . . . . . . . . . . . . 45 4.2.4 Number of Sensors M... 45 4.5 Standard deviation vs. Ns. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 4.6 Bias...laboratory MTM multiple taper method MUSIC multiple signal classification MVDR minimum variance distortionless reposnse PSK phase shift keying QAM

Multiple Source DF (Direction Finding) Signal Processing: An Experimental System,

DTIC Science & Technology

The MUltiple SIgnal Characterization ( MUSIC ) algorithm is an implementation of the Signal Subspace Approach to provide parameter estimates of...the signal subspace (obtained from the received data) and the array manifold (obtained via array calibration). The MUSIC algorithm has been

Physiological properties of brain-machine interface input signals.

PubMed

Slutzky, Marc W; Flint, Robert D

2017-08-01

Brain-machine interfaces (BMIs), also called brain-computer interfaces (BCIs), decode neural signals and use them to control some type of external device. Despite many experimental successes and terrific demonstrations in animals and humans, a high-performance, clinically viable device has not yet been developed for widespread usage. There are many factors that impact clinical viability and BMI performance. Arguably, the first of these is the selection of brain signals used to control BMIs. In this review, we summarize the physiological characteristics and performance-including movement-related information, longevity, and stability-of multiple types of input signals that have been used in invasive BMIs to date. These include intracortical spikes as well as field potentials obtained inside the cortex, at the surface of the cortex (electrocorticography), and at the surface of the dura mater (epidural signals). We also discuss the potential for future enhancements in input signal performance, both by improving hardware and by leveraging the knowledge of the physiological characteristics of these signals to improve decoding and stability. Copyright © 2017 the American Physiological Society.

Inhibiting core fucosylation attenuates glucose-induced peritoneal fibrosis in rats.

PubMed

Li, Longkai; Shen, Nan; Wang, Nan; Wang, Weidong; Tang, Qingzhu; Du, Xiangning; Carrero, Juan Jesus; Wang, Keping; Deng, Yiyao; Li, Zhitong; Lin, Hongli; Wu, Taihua

2018-06-01

Ultrafiltration failure is a major complication of long-term peritoneal dialysis, resulting in dialysis failure. Peritoneal fibrosis induced by continuous exposure to high glucose dialysate is the major contributor of ultrafiltration failure, for which there is no effective treatment. Overactivation of several signaling pathways, including transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) pathways, contribute to the development of peritoneal fibrosis. Therefore, simultaneously blocking multiple signaling pathways might be a potential novel method of treating peritoneal fibrosis. Previously, we showed that core fucosylation, an important posttranslational modification of the TGF-β1 receptors, can regulate the activation of TGF-β1 signaling in renal interstitial fibrosis. However, it remains unclear whether core fucosylation affects the progression of peritoneal fibrosis. Herein, we show that core fucosylation was enriched in the peritoneal membrane of rats accompanied by peritoneal fibrosis induced by a high glucose dialysate. Blocking core fucosylation dramatically attenuated peritoneal fibrosis in the rat model achieved by simultaneously inactivating the TGF-β1 and PDGF signaling pathways. Next the protective effects of blocking core fucosylation and imatinib (a selective PDGF receptor inhibitor) on peritoneal fibrosis were compared and found to exhibit a greater inhibitory effect over imatinib alone, suggesting that blocking activation of multiple signaling pathways may have superior inhibitory effects on the development of peritoneal fibrosis. Thus, core fucosylation is essential for the development of peritoneal fibrosis by regulating the activation of multiple signaling pathways. This may be a potential novel target for drug development to treat peritoneal fibrosis. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

A Pivotal Role of DELLAs in Regulating Multiple Hormone Signals.

PubMed

Davière, Jean-Michel; Achard, Patrick

2016-01-04

Plant phenotypic plasticity is controlled by diverse hormone pathways, which integrate and convey information from multiple developmental and environmental signals. Moreover, in plants many processes such as growth, development, and defense are regulated in similar ways by multiple hormones. Among them, gibberellins (GAs) are phytohormones with pleiotropic actions, regulating various growth processes throughout the plant life cycle. Previous work has revealed extensive interplay between GAs and other hormones, but the molecular mechanism became apparent only recently. Molecular and physiological studies have demonstrated that DELLA proteins, considered as master negative regulators of GA signaling, integrate multiple hormone signaling pathways through physical interactions with transcription factors or regulatory proteins from different families. In this review, we summarize the latest progress in GA signaling and its direct crosstalk with the main phytohormone signaling, emphasizing the multifaceted role of DELLA proteins with key components of major hormone signaling pathways. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Inflammatory Mediators Alter the Astrocyte Transcriptome and Calcium Signaling Elicited by Multiple G-Protein-Coupled Receptors

PubMed Central

Hamby, Mary E.; Coppola, Giovanni; Ao, Yan; Geschwind, Daniel H.; Khakh, Baljit S.; Sofroniew, Michael V.

2012-01-01

Inflammation features in CNS disorders such as stroke, trauma, neurodegeneration, infection, and autoimmunity in which astrocytes play critical roles. To elucidate how inflammatory mediators alter astrocyte functions, we examined effects of transforming growth factor-β1 (TGF-β1), lipopolysaccharide (LPS), and interferon-gamma (IFNγ), alone and in combination, on purified, mouse primary cortical astrocyte cultures. We used microarrays to conduct whole-genome expression profiling, and measured calcium signaling, which is implicated in mediating dynamic astrocyte functions. Combinatorial exposure to TGF-β1, LPS, and IFNγ significantly modulated astrocyte expression of >6800 gene probes, including >380 synergistic changes not predicted by summing individual treatment effects. Bioinformatic analyses revealed significantly and markedly upregulated molecular networks and pathways associated in particular with immune signaling and regulation of cell injury, death, growth, and proliferation. Highly regulated genes included chemokines, growth factors, enzymes, channels, transporters, and intercellular and intracellular signal transducers. Notably, numerous genes for G-protein-coupled receptors (GPCRs) and G-protein effectors involved in calcium signaling were significantly regulated, mostly down (for example, Cxcr4, Adra2a, Ednra, P2y1, Gnao1, Gng7), but some up (for example, P2y14, P2y6, Ccrl2, Gnb4). We tested selected cases and found that changes in GPCR gene expression were accompanied by significant, parallel changes in astrocyte calcium signaling evoked by corresponding GPCR-specific ligands. These findings identify pronounced changes in the astrocyte transcriptome induced by TGF-β1, LPS, and IFNγ, and show that these inflammatory stimuli upregulate astrocyte molecular networks associated with immune- and injury-related functions and significantly alter astrocyte calcium signaling stimulated by multiple GPCRs. PMID:23077035

β catenin in health: A review

PubMed Central

Prakash, Sharada; Swaminathan, Uma

2015-01-01

β catenin belongs to the armadillo family of proteins. It plays a crucial role in developmental and homeostatic processes. Wnts are a family of 19 secreted glycoproteins that transduce multiple signaling cascades, including the canonical Wnt/β catenin pathway, Wnt/Ca2+ pathway and the Wnt/polarity pathway. This is a review on β catenin, Wnt proteins and their secretion, the signaling pathway, the associated factors and the crucial role of β catenin in odontogenesis. PMID:26604501

The Hippo Pathway: Immunity and Cancer

PubMed Central

J. Janse van Rensburg, Helena

2018-01-01

Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats. We further discuss how Hippo signaling functions as part of an immune response. Finally, we review how immune cell-intrinsic Hippo signaling modulates the development/function of leukocytes and propose directions for future work. PMID:29597279

Navigation system and method

NASA Technical Reports Server (NTRS)

Taylor, R. E.; Sennott, J. W. (Inventor)

1984-01-01

In a global positioning system (GPS), such as the NAVSTAR/GPS system, wherein the position coordinates of user terminals are obtained by processing multiple signals transmitted by a constellation of orbiting satellites, an acquisition-aiding signal generated by an earth-based control station is relayed to user terminals via a geostationary satellite to simplify user equipment. The aiding signal is FSK modulated on a reference channel slightly offset from the standard GPS channel. The aiding signal identifies satellites in view having best geometry and includes Doppler prediction data as well as GPS satellite coordinates and identification data associated with user terminals within an area being served by the control station and relay satellite. The aiding signal significantly reduces user equipment by simplifying spread spectrum signal demodulation and reducing data processing functions previously carried out at the user terminals.

Cross-beam coherence of infrasonic signals at local and regional ranges.

PubMed

Alberts, W C Kirkpatrick; Tenney, Stephen M

2017-11-01

Signals collected by infrasound arrays require continuous analysis by skilled personnel or by automatic algorithms in order to extract useable information. Typical pieces of information gained by analysis of infrasonic signals collected by multiple sensor arrays are arrival time, line of bearing, amplitude, and duration. These can all be used, often with significant accuracy, to locate sources. A very important part of this chain is associating collected signals across multiple arrays. Here, a pairwise, cross-beam coherence method of signal association is described that allows rapid signal association for high signal-to-noise ratio events captured by multiple infrasound arrays at ranges exceeding 150 km. Methods, test cases, and results are described.

Dysregulation of Uterine Signaling Pathways in Progesterone Receptor-Cre Knockout of Dicer

PubMed Central

Andreu-Vieyra, Claudia V.; Kim, Tae Hoon; Jeong, Jae-Wook; Hodgson, Myles C.; Chen, Ruihong; Creighton, Chad J.; Lydon, John P.; Gunaratne, Preethi H.; DeMayo, Francesco J.; Matzuk, Martin M.

2012-01-01

Epithelial-stromal interactions in the uterus are required for normal uterine functions such as pregnancy, and multiple signaling pathways are essential for this process. Although Dicer and microRNA (miRNA) have been implicated in several reproductive processes, the specific roles of Dicer and miRNA in uterine development are not known. To address the roles of miRNA in the regulation of key uterine pathways, we generated a conditional knockout of Dicer in the postnatal uterine epithelium and stroma using progesterone receptor-Cre. These Dicer conditional knockout females are sterile with small uteri, which demonstrate significant defects, including absence of glandular epithelium and enhanced stromal apoptosis, beginning at approximately postnatal d 15, with coincident expression of Cre and deletion of Dicer. Specific miRNA (miR-181c, −200b, −101, let-7d) were down-regulated and corresponding predicted proapoptotic target genes (Bcl2l11, Aldh1a3) were up-regulated, reflecting the apoptotic phenomenon. Although these mice had normal serum hormone levels, critical uterine signaling pathways, including progesterone-responsive genes, Indian hedgehog signaling, and the Wnt/β-catenin canonical pathway, were dysregulated at the mRNA level. Importantly, uterine stromal cell proliferation in response to progesterone was absent, whereas uterine epithelial cell proliferation in response to estradiol was maintained in adult uteri. These data implicate Dicer and appropriate miRNA expression as essential players in the regulation of multiple uterine signaling pathways required for uterine development and appropriate function. PMID:22798293

Frodo proteins: modulators of Wnt signaling in vertebrate development.

PubMed

Brott, Barbara K; Sokol, Sergei Y

2005-09-01

The Frodo/dapper (Frd) proteins are recently discovered signaling adaptors, which functionally and physically interact with Wnt and Nodal signaling pathways during vertebrate development. The Frd1 and Frd2 genes are expressed in dynamic patterns in early embryos, frequently in cells undergoing epithelial-mesenchymal transition. The Frd proteins function in multiple developmental processes, including mesoderm and neural tissue specification, early morphogenetic cell movements, and organogenesis. Loss-of-function studies using morpholino antisense oligonucleotides demonstrate that the Frd proteins regulate Wnt signal transduction in a context-dependent manner and may be involved in Nodal signaling. The identification of Frd-associated factors and cellular targets of the Frd proteins should shed light on the molecular mechanisms underlying Frd functions in embryonic development and in cancer.

Extracellular cyclophilin-A stimulates ERK1/2 phosphorylation in a cell-dependent manner but broadly stimulates nuclear factor kappa B

PubMed Central

2012-01-01

Background Although the peptidyl-prolyl isomerase, cyclophilin-A (peptidyl-prolyl isomerase, PPIA), has been studied for decades in the context of its intracellular functions, its extracellular roles as a major contributor to both inflammation and multiple cancers have more recently emerged. A wide range of activities have been ascribed to extracellular PPIA that include induction of cytokine and matrix metalloproteinase (MMP) secretion, which potentially underlie its roles in inflammation and tumorigenesis. However, there have been conflicting reports as to which particular signaling events are under extracellular PPIA regulation, which may be due to either cell-dependent responses and/or the use of commercial preparations recently shown to be highly impure. Methods We have produced and validated the purity of recombinant PPIA in order to subject it to a comparative analysis between different cell types. Specifically, we have used a combination of multiple methods such as luciferase reporter screens, translocation assays, phosphorylation assays, and nuclear magnetic resonance to compare extracellular PPIA activities in several different cell lines that included epithelial and monocytic cells. Results Our findings have revealed that extracellular PPIA activity is cell type-dependent and that PPIA signals via multiple cellular receptors beyond the single transmembrane receptor previously identified, Extracellular Matrix MetalloPRoteinase Inducer (EMMPRIN). Finally, while our studies provide important insight into the cell-specific responses, they also indicate that there are consistent responses such as nuclear factor kappa B (NFκB) signaling induced in all cell lines tested. Conclusions We conclude that although extracellular PPIA activates several common pathways, it also targets different receptors in different cell types, resulting in a complex, integrated signaling network that is cell type-specific. PMID:22631225

Strategies for Increasing Pancreatic Tumor Immunogenicity

PubMed Central

Johnson, Burles A.; Yarchoan, Mark; Lee, Valerie; Laheru, Daniel A.; Jaffee, Elizabeth M.

2017-01-01

Immunotherapy has changed the standard of care for multiple deadly cancers including lung, head and neck, gastric, and some colorectal cancers. However, single agent immunotherapy has had little effect in pancreatic adenocarcinoma (PDAC). Increasing evidence suggests that the PDAC microenvironment is comprised of an intricate network of signals between immune cells, PDAC cells, and stroma, resulting in an immunosuppressive environment resistant to single agent immunotherapies. In this review, we discuss differences between immunotherapy sensitive cancers and PDAC, the complex interactions between PDAC stroma and suppressive tumor infiltrating cells that facilitate PDAC development and progression, the immunologic targets within these complex networks that are drugable, and data supporting combination drug approaches that modulate multiple PDAC signals, which should lead to improved clinical outcomes. PMID:28373364

O-GlcNAcylation in Cancer Biology: Linking Metabolism and Signaling.

PubMed

Ferrer, Christina M; Sodi, Valerie L; Reginato, Mauricio J

2016-08-14

The hexosamine biosynthetic pathway (HBP) is highly dependent on multiple metabolic nutrients including glucose, glutamine, and acetyl-CoA. Increased flux through HBP leads to elevated post-translational addition of β-D-N-acetylglucosamine sugars to nuclear and cytoplasmic proteins. Increased total O-GlcNAcylation is emerging as a general characteristic of cancer cells, and recent studies suggest that O-GlcNAcylation is a central communicator of nutritional status to control key signaling and metabolic pathways that regulate multiple cancer cell phenotypes. This review summarizes our current understanding of changes of O-GlcNAc cycling enzymes in cancer, the role of O-GlcNAcylation in tumorigenesis, and the current challenges in targeting this pathway therapeutically. Copyright © 2016 Elsevier Ltd. All rights reserved.

High frequency modulation circuits based on photoconductive wide bandgap switches

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

Sampayan, Stephen

Methods, systems, and devices for high voltage and/or high frequency modulation. In one aspect, an optoelectronic modulation system includes an array of two or more photoconductive switch units each including a wide bandgap photoconductive material coupled between a first electrode and a second electrode, a light source optically coupled to the WBGP material of each photoconductive switch unit via a light path, in which the light path splits into multiple light paths to optically interface with each WBGP material, such that a time delay of emitted light exists along each subsequent split light path, and in which the WBGP materialmore » conducts an electrical signal when a light signal is transmitted to the WBGP material, and an output to transmit the electrical signal conducted by each photoconductive switch unit. The time delay of the photons emitted through the light path is substantially equivalent to the time delay of the electrical signal.« less

New insights into IGF-1 signaling in the heart.

PubMed

Troncoso, Rodrigo; Ibarra, Cristián; Vicencio, Jose Miguel; Jaimovich, Enrique; Lavandero, Sergio

2014-03-01

Insulin-like growth factor 1 (IGF-1) signaling regulates contractility, metabolism, hypertrophy, autophagy, senescence, and apoptosis in the heart. IGF-1 deficiency is associated with an increased risk of cardiovascular disease, whereas cardiac activation of IGF-1 receptor (IGF-1R) protects from the detrimental effects of a high-fat diet and myocardial infarction. IGF-1R activates multiple pathways through its intrinsic tyrosine kinase activity and through coupling to heterotrimeric G protein. These pathways involve classic second messengers, phosphorylation cascades, lipid signaling, Ca(2+) transients, and gene expression. In addition, IGF-1R triggers signaling in different subcellular locations including the plasma membrane, perinuclear T tubules, and also in internalized vesicles. In this review, we provide a fresh and updated view of the complex IGF-1 scenario in the heart, including a critical focus on therapeutic strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Software system for data management and distributed processing of multichannel biomedical signals.

PubMed

Franaszczuk, P J; Jouny, C C

2004-01-01

The presented software is designed for efficient utilization of cluster of PC computers for signal analysis of multichannel physiological data. The system consists of three main components: 1) a library of input and output procedures, 2) a database storing additional information about location in a storage system, 3) a user interface for selecting data for analysis, choosing programs for analysis, and distributing computing and output data on cluster nodes. The system allows for processing multichannel time series data in multiple binary formats. The description of data format, channels and time of recording are included in separate text files. Definition and selection of multiple channel montages is possible. Epochs for analysis can be selected both manually and automatically. Implementation of a new signal processing procedures is possible with a minimal programming overhead for the input/output processing and user interface. The number of nodes in cluster used for computations and amount of storage can be changed with no major modification to software. Current implementations include the time-frequency analysis of multiday, multichannel recordings of intracranial EEG of epileptic patients as well as evoked response analyses of repeated cognitive tasks.

Structural characterization of sulfated steroids that activate mouse pheromone-sensing neurons.

PubMed

Hsu, Fong-Fu; Nodari, Francesco; Kao, Lung-Fa; Fu, Xiaoyan; Holekamp, Terrence F; Turk, John; Holy, Timothy E

2008-12-30

In many species, social behavior is organized via chemical signaling. While many of these signals have been identified for insects, the chemical identity of these social cues (often called pheromones) for mammals is largely unknown. We recently isolated these chemical cues that caused firing in the pheromone-sensing neurons of the vomeronasal organ from female mouse urine [Nodari, F., et al. (2008) J. Neurosci. 28, 6407-6418]. Here, we report their structural characterization. Mass spectrometric approaches, including tandem quadrupole, multiple-stage linear ion trap, high-resolution mass spectrometry, and H-D exchange followed by ESI mass spectrometry, along with (1)H and (13)C nuclear magnetic resonance spectroscopy, including two-dimensional correlation spectroscopy, total correlation spectroscopy, heteronuclear multiple-quantum coherence, and NOE, were used to identify two sulfated steroids, 4-pregnene-11beta,20,21-triol-3-one 21-sulfate (I) (the configuration at C20 was not deduced) and 4-pregnene-11beta,21-diol-3,20-dione 21-sulfate (II), whose presence is sex-specific. The identification of this novel class of mammalian social signaling compounds suggests that steroid hormones, upon conjugation, assume a new biological role, conveying information about the organism's identity and physiological state.

SETI Observations of Exoplanets with the Allen Telescope Array

NASA Astrophysics Data System (ADS)

Harp, G. R.; Richards, Jon; Tarter, Jill C.; Dreher, John; Jordan, Jane; Shostak, Seth; Smolek, Ken; Kilsdonk, Tom; Wilcox, Bethany R.; Wimberly, M. K. R.; Ross, John; Barott, W. C.; Ackermann, R. F.; Blair, Samantha

2016-12-01

We report radio SETI observations on a large number of known exoplanets and other nearby star systems using the Allen Telescope Array (ATA). Observations were made over about 19000 hr from 2009 May to 2015 December. This search focused on narrowband radio signals from a set totaling 9293 stars, including 2015 exoplanet stars and Kepler objects of interest and an additional 65 whose planets may be close to their habitable zones. The ATA observations were made using multiple synthesized beams and an anticoincidence filter to help identify terrestrial radio interference. Stars were observed over frequencies from 1 to 9 GHz in multiple bands that avoid strong terrestrial communication frequencies. Data were processed in near-real time for narrowband (0.7-100 Hz) continuous and pulsed signals with transmitter/receiver relative accelerations from -0.3 to 0.3 m s-2. A total of 1.9 × 108 unique signals requiring immediate follow-up were detected in observations covering more than 8 × 106 star-MHz. We detected no persistent signals from extraterrestrial technology exceeding our frequency-dependent sensitivity threshold of 180-310 × 10-26 W m-2.

A dynamic multi-channel speech enhancement system for distributed microphones in a car environment

NASA Astrophysics Data System (ADS)

Matheja, Timo; Buck, Markus; Fingscheidt, Tim

2013-12-01

Supporting multiple active speakers in automotive hands-free or speech dialog applications is an interesting issue not least due to comfort reasons. Therefore, a multi-channel system for enhancement of speech signals captured by distributed distant microphones in a car environment is presented. Each of the potential speakers in the car has a dedicated directional microphone close to his position that captures the corresponding speech signal. The aim of the resulting overall system is twofold: On the one hand, a combination of an arbitrary pre-defined subset of speakers' signals can be performed, e.g., to create an output signal in a hands-free telephone conference call for a far-end communication partner. On the other hand, annoying cross-talk components from interfering sound sources occurring in multiple different mixed output signals are to be eliminated, motivated by the possibility of other hands-free applications being active in parallel. The system includes several signal processing stages. A dedicated signal processing block for interfering speaker cancellation attenuates the cross-talk components of undesired speech. Further signal enhancement comprises the reduction of residual cross-talk and background noise. Subsequently, a dynamic signal combination stage merges the processed single-microphone signals to obtain appropriate mixed signals at the system output that may be passed to applications such as telephony or a speech dialog system. Based on signal power ratios between the particular microphone signals, an appropriate speaker activity detection and therewith a robust control mechanism of the whole system is presented. The proposed system may be dynamically configured and has been evaluated for a car setup with four speakers sitting in the car cabin disturbed in various noise conditions.

Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer

PubMed Central

Kaur, Sukhbir

2017-01-01

Abstract Significance: In contrast to structural elements of the extracellular matrix, matricellular proteins appear transiently during development and injury responses, but their sustained expression can contribute to chronic disease. Through interactions with other matrix components and specific cell surface receptors, matricellular proteins regulate multiple signaling pathways, including those mediated by reactive oxygen and nitrogen species and H2S. Dysregulation of matricellular proteins contributes to the pathogenesis of vascular diseases and cancer. Defining the molecular mechanisms and receptors involved is revealing new therapeutic opportunities. Recent Advances: Thrombospondin-1 (TSP1) regulates NO, H2S, and superoxide production and signaling in several cell types. The TSP1 receptor CD47 plays a central role in inhibition of NO signaling, but other TSP1 receptors also modulate redox signaling. The matricellular protein CCN1 engages some of the same receptors to regulate redox signaling, and ADAMTS1 regulates NO signaling in Marfan syndrome. In addition to mediating matricellular protein signaling, redox signaling is emerging as an important pathway that controls the expression of several matricellular proteins. Critical Issues: Redox signaling remains unexplored for many matricellular proteins. Their interactions with multiple cellular receptors remains an obstacle to defining signaling mechanisms, but improved transgenic models could overcome this barrier. Future Directions: Therapeutics targeting the TSP1 receptor CD47 may have beneficial effects for treating cardiovascular disease and cancer and have recently entered clinical trials. Biomarkers are needed to assess their effects on redox signaling in patients and to evaluate how these contribute to their therapeutic efficacy and potential side effects. Antioxid. Redox Signal. 27, 874–911. PMID:28712304

Signal transduction during wheat grain development.

PubMed

Kong, Lingan; Guo, Honghai; Sun, Mingze

2015-04-01

This review examines the signaling pathways from the developmental and environmental point of view and the interactions among external conditions, hormonal regulations, and sugarsensing in wheat. Grain development is the key phase of reproductive growth that is closely associated with vegetative organ senescence, initiation of grain filling, pre-stored assimilates remobilization, and maturation. Senescence is characterized by loss of chlorophyll and the degradation of proteins, nucleic acids, lipids as well as nutrient exports to the sink. The initiation and progression of vegetative organ senescence are under the control of an array of environmental signals (such as biotic and abiotic stresses, darkness, and nutrient availability) and endogenous factors (including aging, multiple hormones, and sugar availability). This review will discuss the major breakthroughs in signal transduction for the wheat (Triticum aestivum) grain development achieved in the past several years, with focuses on the regulation of senescence, reserves remobilization and biosynthesis of main components of the grain. Different mechanisms of diverse signals in controlling different phrases of wheat grain development, and cross talks between different signaling pathways will also be discussed. For perspectives, key signaling networks for grain development remain to be elucidated, including cross talks and the interactions between various environmental factors and internal signals.

ISLE (Image and Signal LISP Environment): A functional language interface for signal and image processing

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

Azevedo, S.G.; Fitch, J.P.

1987-10-21

Conventional software interfaces that use imperative computer commands or menu interactions are often restrictive environments when used for researching new algorithms or analyzing processed experimental data. We found this to be true with current signal-processing software (SIG). As an alternative, ''functional language'' interfaces provide features such as command nesting for a more natural interaction with the data. The Image and Signal LISP Environment (ISLE) is an example of an interpreted functional language interface based on common LISP. Advantages of ISLE include multidimensional and multiple data-type independence through dispatching functions, dynamic loading of new functions, and connections to artificial intelligence (AI)more » software. 10 refs.« less

ISLE (Image and Signal Lisp Environment): A functional language interface for signal and image processing

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

Azevedo, S.G.; Fitch, J.P.

1987-05-01

Conventional software interfaces which utilize imperative computer commands or menu interactions are often restrictive environments when used for researching new algorithms or analyzing processed experimental data. We found this to be true with current signal processing software (SIG). Existing ''functional language'' interfaces provide features such as command nesting for a more natural interaction with the data. The Image and Signal Lisp Environment (ISLE) will be discussed as an example of an interpreted functional language interface based on Common LISP. Additional benefits include multidimensional and multiple data-type independence through dispatching functions, dynamic loading of new functions, and connections to artificial intelligencemore » software.« less

Multiple transmitter performance with appropriate amplitude modulation for free-space optical communication.

PubMed

Tellez, Jason A; Schmidt, Jason D

2011-08-20

The propagation of a free-space optical communications signal through atmospheric turbulence experiences random fluctuations in intensity, including signal fades, which negatively impact the performance of the communications link. The gamma-gamma probability density function is commonly used to model the scintillation of a single beam. One proposed method to reduce the occurrence of scintillation-induced fades at the receiver plane involves the use of multiple beams propagating through independent paths, resulting in a sum of independent gamma-gamma random variables. Recently an analytical model for the probability distribution of irradiance from the sum of multiple independent beams was developed. Because truly independent beams are practically impossible to create, we present here a more general but approximate model for the distribution of beams traveling through partially correlated paths. This model compares favorably with wave-optics simulations and highlights the reduced scintillation as the number of transmitted beams is increased. Additionally, a pulse-position modulation scheme is used to reduce the impact of signal fades when they occur. Analytical and simulated results showed significantly improved performance when compared to fixed threshold on/off keying. © 2011 Optical Society of America

IGF system targeted therapy: Therapeutic opportunities for ovarian cancer.

PubMed

Liefers-Visser, J A L; Meijering, R A M; Reyners, A K L; van der Zee, A G J; de Jong, S

2017-11-01

The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Nervous System Complexity Baffles Scientists.

ERIC Educational Resources Information Center

Fox, Jeffrey L.

1982-01-01

New research findings about how nerve cells transmit signals are forcing researchers to overhaul their simplistic ideas about the nervous system. Topics highlighted include the multiple role of peptides in the nervous system, receptor molecules, and molecules that form ion channels within membranes. (Author/JN)

In vitro screening for potential chemical inhibitors of deiodinase type 1 activity

EPA Science Inventory

Control of thyroid hormone (TH) signaling in vertebrates is dependent upon multiple key events including iodide uptake, hormone synthesis, metabolism and elimination, to maintain proper homeostasis of the hormones. Deiodinase enzymes interconvert THs between less active and more...

An integrative model links multiple inputs and signaling pathways to the onset of DNA synthesis in hepatocytes

PubMed Central

Huard, Jérémy; Mueller, Stephanie; Gilles, Ernst D; Klingmüller, Ursula; Klamt, Steffen

2012-01-01

During liver regeneration, quiescent hepatocytes re-enter the cell cycle to proliferate and compensate for lost tissue. Multiple signals including hepatocyte growth factor, epidermal growth factor, tumor necrosis factor α, interleukin-6, insulin and transforming growth factor β orchestrate these responses and are integrated during the G1 phase of the cell cycle. To investigate how these inputs influence DNA synthesis as a measure for proliferation, we established a large-scale integrated logical model connecting multiple signaling pathways and the cell cycle. We constructed our model based upon established literature knowledge, and successively improved and validated its structure using hepatocyte-specific literature as well as experimental DNA synthesis data. Model analyses showed that activation of the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways was sufficient and necessary for triggering DNA synthesis. In addition, we identified key species in these pathways that mediate DNA replication. Our model predicted oncogenic mutations that were compared with the COSMIC database, and proposed intervention targets to block hepatocyte growth factor-induced DNA synthesis, which we validated experimentally. Our integrative approach demonstrates that, despite the complexity and size of the underlying interlaced network, logical modeling enables an integrative understanding of signaling-controlled proliferation at the cellular level, and thus can provide intervention strategies for distinct perturbation scenarios at various regulatory levels. PMID:22443451

Sensory-based niche partitioning in a multiple predator - multiple prey community.

PubMed

Falk, Jay J; ter Hofstede, Hannah M; Jones, Patricia L; Dixon, Marjorie M; Faure, Paul A; Kalko, Elisabeth K V; Page, Rachel A

2015-06-07

Many predators and parasites eavesdrop on the communication signals of their prey. Eavesdropping is typically studied as dyadic predator-prey species interactions; yet in nature, most predators target multiple prey species and most prey must evade multiple predator species. The impact of predator communities on prey signal evolution is not well understood. Predators could converge in their preferences for conspicuous signal properties, generating competition among predators and natural selection on particular prey signal features. Alternatively, predator species could vary in their preferences for prey signal properties, resulting in sensory-based niche partitioning of prey resources. In the Neotropics, many substrate-gleaning bats use the mate-attraction songs of male katydids to locate them as prey. We studied mechanisms of niche partitioning in four substrate-gleaning bat species and found they are similar in morphology, echolocation signal design and prey-handling ability, but each species preferred different acoustic features of male song in 12 sympatric katydid species. This divergence in predator preference probably contributes to the coexistence of many substrate-gleaning bat species in the Neotropics, and the substantial diversity in the mate-attraction signals of katydids. Our results provide insight into how multiple eavesdropping predator species might influence prey signal evolution through sensory-based niche partitioning. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Multiple cytoskeletal pathways and PI3K signaling mediate CDC-42-induced neuronal protrusion in C. elegans.

PubMed

Alan, Jamie K; Struckhoff, Eric C; Lundquist, Erik A

2013-01-01

Rho GTPases are key regulators of cellular protrusion and are involved in many developmental events including axon guidance during nervous system development. Rho GTPase pathways display functional redundancy in developmental events, including axon guidance. Therefore, their roles can often be masked when using simple loss-of-function genetic approaches. As a complement to loss-of-function genetics, we constructed a constitutively activated CDC-42(G12V) expressed in C. elegans neurons. CDC-42(G12V) drove the formation of ectopic lamellipodial and filopodial protrusions in the PDE neurons, which resembled protrusions normally found on migrating growth cones of axons. We then used a candidate gene approach to identify molecules that mediate CDC-42(G12V)-induced ectopic protrusions by determining if loss of function of the genes could suppress CDC-42(G12V). Using this approach, we identified 3 cytoskeletal pathways previously implicated in axon guidance, the Arp2/3 complex, UNC-115/abLIM, and UNC-43/Ena. We also identified the Nck-interacting kinase MIG-15/NIK and p21-activated kinases (PAKs), also implicated in axon guidance. Finally, PI3K signaling was required, specifically the Rictor/mTORC2 branch but not the mTORC1 branch that has been implicated in other aspects of PI3K signaling including stress and aging. Our results indicate that multiple pathways can mediate CDC-42-induced neuronal protrusions that might be relevant to growth cone protrusions during axon pathfinding. Each of these pathways involves Rac GTPases, which might serve to integrate the pathways and coordinate the multiple CDC-42 pathways. These pathways might be relevant to developmental events such as axon pathfinding as well as disease states such as metastatic melanoma.

Multiple cytoskeletal pathways and PI3K signaling mediate CDC-42-induced neuronal protrusion in C. elegans

PubMed Central

Alan, Jamie K; Struckhoff, Eric C; Lundquist, Erik A

2013-01-01

Rho GTPases are key regulators of cellular protrusion and are involved in many developmental events including axon guidance during nervous system development. Rho GTPase pathways display functional redundancy in developmental events, including axon guidance. Therefore, their roles can often be masked when using simple loss-of-function genetic approaches. As a complement to loss-of-function genetics, we constructed a constitutively activated CDC-42(G12V) expressed in C. elegans neurons. CDC-42(G12V) drove the formation of ectopic lamellipodial and filopodial protrusions in the PDE neurons, which resembled protrusions normally found on migrating growth cones of axons. We then used a candidate gene approach to identify molecules that mediate CDC-42(G12V)-induced ectopic protrusions by determining if loss of function of the genes could suppress CDC-42(G12V). Using this approach, we identified 3 cytoskeletal pathways previously implicated in axon guidance, the Arp2/3 complex, UNC-115/abLIM, and UNC-43/Ena. We also identified the Nck-interacting kinase MIG-15/NIK and p21-activated kinases (PAKs), also implicated in axon guidance. Finally, PI3K signaling was required, specifically the Rictor/mTORC2 branch but not the mTORC1 branch that has been implicated in other aspects of PI3K signaling including stress and aging. Our results indicate that multiple pathways can mediate CDC-42-induced neuronal protrusions that might be relevant to growth cone protrusions during axon pathfinding. Each of these pathways involves Rac GTPases, which might serve to integrate the pathways and coordinate the multiple CDC-42 pathways. These pathways might be relevant to developmental events such as axon pathfinding as well as disease states such as metastatic melanoma. PMID:24149939

Messages from the voices within: regulation of signaling by proteins of the nuclear lamina.

PubMed

Gerace, Larry; Tapia, Olga

2018-01-04

The nuclear lamina (NL) is a protein scaffold lining the nuclear envelope that consists of nuclear lamins and associated transmembrane proteins. It helps to organize the nuclear envelope, chromosomes, and the cytoplasmic cytoskeleton. The NL also has an important role in regulation of signaling, as highlighted by the wide range of human diseases caused by mutations in the genes for NL proteins with associated signaling defects. This review will consider diverse mechanisms for signaling regulation by the NL that have been uncovered recently, including interaction with signaling effectors, modulation of actin assembly and compositional alteration of the NL. Cells with discrete NL mutations often show disruption of multiple signaling pathways, however, and for the most part the mechanistic basis for these complex phenotypes remains to be elucidated. Copyright © 2017. Published by Elsevier Ltd.

Mapping the functional versatility and fragility of Ras GTPase signaling circuits through in vitro network reconstitution.

PubMed

Coyle, Scott M; Lim, Wendell A

2016-01-14

The Ras-superfamily GTPases are central controllers of cell proliferation and morphology. Ras signaling is mediated by a system of interacting molecules: upstream enzymes (GEF/GAP) regulate Ras's ability to recruit multiple competing downstream effectors. We developed a multiplexed, multi-turnover assay for measuring the dynamic signaling behavior of in vitro reconstituted H-Ras signaling systems. By including both upstream regulators and downstream effectors, we can systematically map how different network configurations shape the dynamic system response. The concentration and identity of both upstream and downstream signaling components strongly impacted the timing, duration, shape, and amplitude of effector outputs. The distorted output of oncogenic alleles of Ras was highly dependent on the balance of positive (GAP) and negative (GEF) regulators in the system. We found that different effectors interpreted the same inputs with distinct output dynamics, enabling a Ras system to encode multiple unique temporal outputs in response to a single input. We also found that different Ras-to-GEF positive feedback mechanisms could reshape output dynamics in distinct ways, such as signal amplification or overshoot minimization. Mapping of the space of output behaviors accessible to Ras provides a design manual for programming Ras circuits, and reveals how these systems are readily adapted to produce an array of dynamic signaling behaviors. Nonetheless, this versatility comes with a trade-off of fragility, as there exist numerous paths to altered signaling behaviors that could cause disease.

Optical pulse synthesis using brillouin selective sideband amplification

NASA Technical Reports Server (NTRS)

Yao, X. Steve (Inventor)

2002-01-01

Techniques for producing optical pulses based on Brillouin selective sideband amplification by using a common modulation control signal to modulate both a signal beam to produce multiple sideband signals and a single pump beam to produce multiple pump beams.

Adaptation of the Electra Radio to Support Multiple Receive Channels

NASA Technical Reports Server (NTRS)

Satorius, Edgar H.; Shah, Biren N.; Bruvold, Kristoffer N.; Bell, David J.

2011-01-01

Proposed future Mars missions plan communication between multiple assets (rovers). This paper presents the results of a study carried out to assess the potential adaptation of the Electra radio to a multi-channel transceiver. The basic concept is a Frequency Division multiplexing (FDM) communications scheme wherein different receiver architectures are examined. Options considered include: (1) multiple IF slices, A/D and FPGAs each programmed with an Electra baseband modem; (2) common IF but multiple A/Ds and FPGAs and (3) common IF, single A/D and single or multiple FPGAs programmed to accommodate the FDM signals. These options represent the usual tradeoff between analog and digital complexity. Given the space application, a common IF is preferable; however, multiple users present dynamic range challenges (e.g., near-far constraints) that would favor multiple IF slices (Option 1). Vice versa, with a common IF and multiple A/Ds (Option 2), individual AGC control of the A/Ds would be an important consideration. Option 3 would require a common AGC control strategy and would entail multiple digital down conversion paths within the FPGA. In this paper, both FDM parameters as well as the different Electra design options will be examined. In particular, signal channel spacing as a function of user data rates and transmit powers will be evaluated. In addition, tradeoffs between the different Electra design options will be presented with the ultimate goal of defining an augmented Electra radio architecture for potential future missions.

Endocannabinoid system: potential novel targets for treatment of schizophrenia.

PubMed

Saito, Atsushi; Ballinger, Michael D L; Pletnikov, Mikhail V; Wong, Dean F; Kamiya, Atsushi

2013-05-01

Accumulating epidemiological evidences suggest that cannabis use during adolescence is a potential environmental risk for the development of psychosis, including schizophrenia. Consistently, clinical and preclinical studies, using pharmacological approaches and genetically engineered animals to target endocannabinoid signaling, reveal the multiple varieties of endocannabinoid system-mediated human and animal behaviors, including cognition and emotion. Recently, there has been substantial progress in understanding the molecular mechanisms of the endocannabinoid system for synaptic communications in the central nervous system. Furthermore, the impact of endocannabinoid signaling on diverse cellular processes during brain development has emerged. Thus, although schizophrenia has etiological complexities, including genetic heterogeneities and multiple environmental factors, it now becomes crucial to explore molecular pathways of convergence of genetic risk factors and endocannabinoid signaling, which may provide us with clues to find novel targets for therapeutic intervention. In this review, epidemiological, clinical, and pathological evidences on the role of the endocannabinoid system in the pathophysiologies of schizophrenia will be presented. We will also make a brief overview of the recent progress in understanding molecular mechanisms of the endocannabinoid system for brain development and function, with particular focus on cannabinoid receptor type 1 (CB1R)-mediated cascade, the most well-characterized cannabinoid receptor. Lastly, we will discuss the potential of the endocannabinoid system in finding novel therapeutic targets for prevention and treatment of schizophrenia. Copyright © 2012 Elsevier Inc. All rights reserved.

Multiple-access phased array antenna simulator for a digital beam-forming system investigation

NASA Technical Reports Server (NTRS)

Kerczewski, Robert J.; Yu, John; Walton, Joanne C.; Perl, Thomas D.; Andro, Monty; Alexovich, Robert E.

1992-01-01

Future versions of data relay satellite systems are currently being planned by NASA. Being given consideration for implementation are on-board digital beamforming techniques which will allow multiple users to simultaneously access a single S-band phased array antenna system. To investigate the potential performance of such a system, a laboratory simulator has been developed at NASA's Lewis Research Center. This paper describes the system simulator, and in particular, the requirements, design and performance of a key subsystem, the phased array antenna simulator, which provides realistic inputs to the digital processor including multiple signals, noise, and nonlinearities.

Multiple-access phased array antenna simulator for a digital beam forming system investigation

NASA Technical Reports Server (NTRS)

Kerczewski, Robert J.; Yu, John; Walton, Joanne C.; Perl, Thomas D.; Andro, Monty; Alexovich, Robert E.

1992-01-01

Future versions of data relay satellite systems are currently being planned by NASA. Being given consideration for implementation are on-board digital beamforming techniques which will allow multiple users to simultaneously access a single S-band phased array antenna system. To investigate the potential performance of such a system, a laboratory simulator has been developed at NASA's Lewis Research Center. This paper describes the system simulator, and in particular, the requirements, design, and performance of a key subsystem, the phased array antenna simulator, which provides realistic inputs to the digital processor including multiple signals, noise, and nonlinearities.

Screening the ToxCast Phase 1 chemical library for inhibition of deiodinase type 1 activity

EPA Science Inventory

Thyroid hormone (TH) homeostasis is dependent upon coordination of multiple key events including iodide uptake, hormone synthesis, metabolism and elimination, to maintain proper TH signaling. Deiodinase enzymes catalyze iodide release from THs to interconvert THs between active a...

Screening the ToxCast Phase I Chemical Library for inhibition of Deiodinase Type I enzyme activity

EPA Science Inventory

Thyroid hormone (TH) signaling in vertebrates is dependent upon coordination of multiple key events including iodide uptake, hormone synthesis, metabolism and elimination, to maintain proper homeostasis of the hormones. Deiodinase enzymes interconvert THs between less active and...

Development of automated high throughput single molecular microfluidic detection platform for signal transduction analysis

NASA Astrophysics Data System (ADS)

Huang, Po-Jung; Baghbani Kordmahale, Sina; Chou, Chao-Kai; Yamaguchi, Hirohito; Hung, Mien-Chie; Kameoka, Jun

2016-03-01

Signal transductions including multiple protein post-translational modifications (PTM), protein-protein interactions (PPI), and protein-nucleic acid interaction (PNI) play critical roles for cell proliferation and differentiation that are directly related to the cancer biology. Traditional methods, like mass spectrometry, immunoprecipitation, fluorescence resonance energy transfer, and fluorescence correlation spectroscopy require a large amount of sample and long processing time. "microchannel for multiple-parameter analysis of proteins in single-complex (mMAPS)"we proposed can reduce the process time and sample volume because this system is composed by microfluidic channels, fluorescence microscopy, and computerized data analysis. In this paper, we will present an automated mMAPS including integrated microfluidic device, automated stage and electrical relay for high-throughput clinical screening. Based on this result, we estimated that this automated detection system will be able to screen approximately 150 patient samples in a 24-hour period, providing a practical application to analyze tissue samples in a clinical setting.

ACIRF user's guide: Theory and examples

NASA Astrophysics Data System (ADS)

Dana, Roger A.

1989-12-01

Design and evaluation of radio frequency systems that must operate through ionospheric disturbances resulting from high altitude nuclear detonations requires an accurate channel model. This model must include the effects of high gain antennas that may be used to receive the signals. Such a model can then be used to construct realizations of the received signal for use in digital simulations of trans-ionospheric links or for use in hardware channel simulators. The FORTRAN channel model ACIRF (Antenna Channel Impulse Response Function) generates random realizations of the impulse response function at the outputs of multiple antennas. This user's guide describes the FORTRAN program ACIRF (version 2.0) that generates realizations of channel impulse response functions at the outputs of multiple antennas with arbitrary beamwidths, pointing angles, and relatives positions. This channel model is valid under strong scattering conditions when Rayleigh fading statistics apply. Both frozen-in and turbulent models for the temporal fluctuations are included in this version of ACIRF. The theory of the channel model is described and several examples are given.

Cellular computational platform and neurally inspired elements thereof

DOEpatents

Okandan, Murat

2016-11-22

A cellular computational platform is disclosed that includes a multiplicity of functionally identical, repeating computational hardware units that are interconnected electrically and optically. Each computational hardware unit includes a reprogrammable local memory and has interconnections to other such units that have reconfigurable weights. Each computational hardware unit is configured to transmit signals into the network for broadcast in a protocol-less manner to other such units in the network, and to respond to protocol-less broadcast messages that it receives from the network. Each computational hardware unit is further configured to reprogram the local memory in response to incoming electrical and/or optical signals.

Clicks, whistles and pulses: Passive and active signal use in dolphin communication

NASA Astrophysics Data System (ADS)

Herzing, Denise L.

2014-12-01

The search for signals out of noise is a problem not only with radio signals from the sky but in the study of animal communication. Dolphins use multiple modalities to communicate including body postures, touch, vision, and most elaborately sound. Like SETI radio signal searches, dolphin sound analysis includes the detection, recognition, analysis, and interpretation of signals. Dolphins use both passive listening and active production to communicate. Dolphins use three main types of acoustic signals: frequency modulated whistles (narrowband with harmonics), echolocation (broadband clicks) and burst pulsed sounds (packets of closely spaced broadband clicks). Dolphin sound analysis has focused on frequency-modulated whistles, yet the most commonly used signals are burst-pulsed sounds which, due to their graded and overlapping nature and bimodal inter-click interval (ICI) rates are hard to categorize. We will look at: 1) the mechanism of sound production and categories of sound types, 2) sound analysis techniques and information content, and 3) examples of lessons learned in the study of dolphin acoustics. The goal of this paper is to provide perspective on how animal communication studies might provide insight to both passive and active SETI in the larger context of searching for life signatures.

Bmp signaling mediates endoderm pouch morphogenesis by regulating Fgf signaling in zebrafish.

PubMed

Lovely, C Ben; Swartz, Mary E; McCarthy, Neil; Norrie, Jacqueline L; Eberhart, Johann K

2016-06-01

The endodermal pouches are a series of reiterated structures that segment the pharyngeal arches and help pattern the vertebrate face. Multiple pathways regulate the complex process of endodermal development, including the Bone morphogenetic protein (Bmp) pathway. However, the role of Bmp signaling in pouch morphogenesis is poorly understood. Using genetic and chemical inhibitor approaches, we show that pouch morphogenesis requires Bmp signaling from 10-18 h post-fertilization, immediately following gastrulation. Blocking Bmp signaling during this window results in morphological defects to the pouches and craniofacial skeleton. Using genetic chimeras we show that Bmp signals directly to the endoderm for proper morphogenesis. Time-lapse imaging and analysis of reporter transgenics show that Bmp signaling is necessary for pouch outpocketing via the Fibroblast growth factor (Fgf) pathway. Double loss-of-function analyses demonstrate that Bmp and Fgf signaling interact synergistically in craniofacial development. Collectively, our analyses shed light on the tissue and signaling interactions that regulate development of the vertebrate face. © 2016. Published by The Company of Biologists Ltd.

Separation of Intercepted Multi-Radar Signals Based on Parameterized Time-Frequency Analysis

NASA Astrophysics Data System (ADS)

Lu, W. L.; Xie, J. W.; Wang, H. M.; Sheng, C.

2016-09-01

Modern radars use complex waveforms to obtain high detection performance and low probabilities of interception and identification. Signals intercepted from multiple radars overlap considerably in both the time and frequency domains and are difficult to separate with primary time parameters. Time-frequency analysis (TFA), as a key signal-processing tool, can provide better insight into the signal than conventional methods. In particular, among the various types of TFA, parameterized time-frequency analysis (PTFA) has shown great potential to investigate the time-frequency features of such non-stationary signals. In this paper, we propose a procedure for PTFA to separate overlapped radar signals; it includes five steps: initiation, parameterized time-frequency analysis, demodulating the signal of interest, adaptive filtering and recovering the signal. The effectiveness of the method was verified with simulated data and an intercepted radar signal received in a microwave laboratory. The results show that the proposed method has good performance and has potential in electronic reconnaissance applications, such as electronic intelligence, electronic warfare support measures, and radar warning.

Bmp signaling mediates endoderm pouch morphogenesis by regulating Fgf signaling in zebrafish

PubMed Central

Swartz, Mary E.; McCarthy, Neil; Norrie, Jacqueline L.; Eberhart, Johann K.

2016-01-01

The endodermal pouches are a series of reiterated structures that segment the pharyngeal arches and help pattern the vertebrate face. Multiple pathways regulate the complex process of endodermal development, including the Bone morphogenetic protein (Bmp) pathway. However, the role of Bmp signaling in pouch morphogenesis is poorly understood. Using genetic and chemical inhibitor approaches, we show that pouch morphogenesis requires Bmp signaling from 10-18 h post-fertilization, immediately following gastrulation. Blocking Bmp signaling during this window results in morphological defects to the pouches and craniofacial skeleton. Using genetic chimeras we show that Bmp signals directly to the endoderm for proper morphogenesis. Time-lapse imaging and analysis of reporter transgenics show that Bmp signaling is necessary for pouch outpocketing via the Fibroblast growth factor (Fgf) pathway. Double loss-of-function analyses demonstrate that Bmp and Fgf signaling interact synergistically in craniofacial development. Collectively, our analyses shed light on the tissue and signaling interactions that regulate development of the vertebrate face. PMID:27122171

Ultrasensitive surveillance of sensors and processes

DOEpatents

Wegerich, Stephan W.; Jarman, Kristin K.; Gross, Kenneth C.

2001-01-01

A method and apparatus for monitoring a source of data for determining an operating state of a working system. The method includes determining a sensor (or source of data) arrangement associated with monitoring the source of data for a system, activating a method for performing a sequential probability ratio test if the data source includes a single data (sensor) source, activating a second method for performing a regression sequential possibility ratio testing procedure if the arrangement includes a pair of sensors (data sources) with signals which are linearly or non-linearly related; activating a third method for performing a bounded angle ratio test procedure if the sensor arrangement includes multiple sensors and utilizing at least one of the first, second and third methods to accumulate sensor signals and determining the operating state of the system.

Ultrasensitive surveillance of sensors and processes

DOEpatents

Wegerich, Stephan W.; Jarman, Kristin K.; Gross, Kenneth C.

1999-01-01

A method and apparatus for monitoring a source of data for determining an operating state of a working system. The method includes determining a sensor (or source of data) arrangement associated with monitoring the source of data for a system, activating a method for performing a sequential probability ratio test if the data source includes a single data (sensor) source, activating a second method for performing a regression sequential possibility ratio testing procedure if the arrangement includes a pair of sensors (data sources) with signals which are linearly or non-linearly related; activating a third method for performing a bounded angle ratio test procedure if the sensor arrangement includes multiple sensors and utilizing at least one of the first, second and third methods to accumulate sensor signals and determining the operating state of the system.

Cited1 Deficiency Suppresses Intestinal Tumorigenesis

PubMed Central

Young, Madeleine; Poetz, Oliver; Parry, Lee; Jenkins, John R.; Williams, Geraint T.; Dunwoodie, Sally L.; Watson, Alastair; Clarke, Alan R.

2013-01-01

Conditional deletion of Apc in the murine intestine alters crypt-villus architecture and function. This process is accompanied by multiple changes in gene expression, including upregulation of Cited1, whose role in colorectal carcinogenesis is unknown. Here we explore the relevance of Cited1 to intestinal tumorigenesis. We crossed Cited1 null mice with ApcMin/+ and AhCre+Apcfl/fl mice and determined the impact of Cited1 deficiency on tumour growth/initiation including tumour multiplicity, cell proliferation, apoptosis and the transcriptome. We show that Cited1 is up-regulated in both human and murine tumours, and that constitutive deficiency of Cited1 increases survival in ApcMin/+ mice from 230.5 to 515 days. However, paradoxically, Cited1 deficiency accentuated nearly all aspects of the immediate phenotype 4 days after conditional deletion of Apc, including an increase in cell death and enhanced perturbation of differentiation, including of the stem cell compartment. Transcriptome analysis revealed multiple pathway changes, including p53, PI3K and Wnt. The activation of Wnt through Cited1 deficiency correlated with increased transcription of β-catenin and increased levels of dephosphorylated β-catenin. Hence, immediately following deletion of Apc, Cited1 normally restrains the Wnt pathway at the level of β-catenin. Thus deficiency of Cited1 leads to hyper-activation of Wnt signaling and an exaggerated Wnt phenotype including elevated cell death. Cited1 deficiency decreases intestinal tumourigenesis in ApcMin/+ mice and impacts upon a number of oncogenic signaling pathways, including Wnt. This restraint imposed by Cited1 is consistent with a requirement for Cited1 to constrain Wnt activity to a level commensurate with optimal adenoma formation and maintenance, and provides one mechanism for tumour repression in the absence of Cited1. PMID:23935526

Multiple Cognitive Control Effects of Error Likelihood and Conflict

PubMed Central

Brown, Joshua W.

2010-01-01

Recent work on cognitive control has suggested a variety of performance monitoring functions of the anterior cingulate cortex, such as errors, conflict, error likelihood, and others. Given the variety of monitoring effects, a corresponding variety of control effects on behavior might be expected. This paper explores whether conflict and error likelihood produce distinct cognitive control effects on behavior, as measured by response time. A change signal task (Brown & Braver, 2005) was modified to include conditions of likely errors due to tardy as well as premature responses, in conditions with and without conflict. The results discriminate between competing hypotheses of independent vs. interacting conflict and error likelihood control effects. Specifically, the results suggest that the likelihood of premature vs. tardy response errors can lead to multiple distinct control effects, which are independent of cognitive control effects driven by response conflict. As a whole, the results point to the existence of multiple distinct cognitive control mechanisms and challenge existing models of cognitive control that incorporate only a single control signal. PMID:19030873

Chemokine receptor binding and signal transduction in native cells of the central nervous system.

PubMed

Davis, Christopher N; Chen, Shuzhen; Boehme, Stefen A; Bacon, Kevin B; Harrison, Jeffrey K

2003-04-01

Chemokine receptors belong to the superfamily of seven-transmembrane-spanning, G-protein-coupled receptors, and their expression by central nervous system cells is clearly documented. As this gene family has become the target of novel therapeutic development, the analysis of these receptors requires radioligand binding techniques as well as methods that entail assessing receptor stimulation of signal transduction pathways. Herein, we describe specific protocols for measuring radiolabeled chemokine binding to their cognate receptors on cultured glial cells as well as to receptors expressed in heterologous cell systems. Multiple downstream signaling pathways, including intracellular calcium influx and receptor-dependent kinase activation, are associated with chemokine receptor stimulation. Protocols for measuring these signaling events in chemokine-receptor-expressing cells are also presented.

Roles for Hedgehog signaling in adult organ homeostasis and repair

PubMed Central

Petrova, Ralitsa; Joyner, Alexandra L.

2014-01-01

The hedgehog (HH) pathway is well known for its mitogenic and morphogenic functions during development, and HH signaling continues in discrete populations of cells within many adult mammalian tissues. Growing evidence indicates that HH regulates diverse quiescent stem cell populations, but the exact roles that HH signaling plays in adult organ homeostasis and regeneration remain poorly understood. Here, we review recently identified functions of HH in modulating the behavior of tissue-specific adult stem and progenitor cells during homeostasis, regeneration and disease. We conclude that HH signaling is a key factor in the regulation of adult tissue homeostasis and repair, acting via multiple different routes to regulate distinct cellular outcomes, including maintenance of plasticity, in a context-dependent manner. PMID:25183867

Design of short-range terahertz wave passive detecting system

NASA Astrophysics Data System (ADS)

Zhang, Chao; Lou, Guowei; Zhu, Li; Qian, Songsong; Li, Ting

2016-09-01

Based on the study of radiation and transmission characteristics on THz waveband, a short-range passive detecting system is designed. The scheme originated from microwave passive detecting system. A prototype was developed following the design of key components including antennas and a harmonic mixer. The system operated at 0.36 THz. A dual-beam Cassegrain antenna was adopted for receiving signals which radiated by object and background. Local oscillator signal was generated by frequency multiplication. Harmonic mixing is adopted for reducing local oscillator signal frequency required by half. Superheterodyne technology is employed for signal acquisition. The system implemented easily. Tests and measurements were taken, which showed that the scheme was feasible and the performance of the prototype system met the design requirements.

An apodized Kepler periodogram for separating planetary and stellar activity signals

PubMed Central

Gregory, Philip C.

2016-01-01

A new apodized Keplerian (AK) model is proposed for the analysis of precision radial velocity (RV) data to model both planetary and stellar activity (SA) induced RV signals. A symmetrical Gaussian apodization function with unknown width and centre can distinguish planetary signals from SA signals on the basis of the span of the apodization window. The general model for m AK signals includes a linear regression term between RV and the SA diagnostic log (R′hk), as well as an extra Gaussian noise term with unknown standard deviation. The model parameters are explored using a Bayesian fusion Markov chain Monte Carlo code. A differential version of the generalized Lomb–Scargle periodogram that employs a control diagnostic provides an additional way of distinguishing SA signals and helps guide the choice of new periods. Results are reported for a recent international RV blind challenge which included multiple state-of-the-art simulated data sets supported by a variety of SA diagnostics. In the current implementation, the AK method achieved a reduction in SA noise by a factor of approximately 6. Final parameter estimates for the planetary candidates are derived from fits that include AK signals to model the SA components and simple Keplerians to model the planetary candidates. Preliminary results are also reported for AK models augmented by a moving average component that allows for correlations in the residuals. PMID:27346979

Purinergic signalling in bone

PubMed Central

Rumney, Robin M. H.; Wang, Ning; Agrawal, Ankita; Gartland, Alison

2012-01-01

Purinergic signaling in bone was first proposed in the early 1990s with the observation that extracellular ATP could modulate events crucial to the normal functioning of bone cells. Since then the expression of nearly all the P2Y and P2X receptors by osteoblasts and osteoclasts has been reported, mediating multiple processes including cell proliferation, differentiation, function, and death. This review will highlight the most recent developments in the field of purinergic signaling in bone, with a special emphasis on recent work resulting from the European Framework 7 funded collaboration ATPBone, as well as Arthritis Research UK and Bone Research Society supported projects. PMID:23049524

BMP signaling in the development of the mouse esophagus and forestomach

PubMed Central

Rodriguez, Pavel; Da Silva, Susana; Oxburgh, Leif; Wang, Fan; Hogan, Brigid L. M.; Que, Jianwen

2010-01-01

The stratification and differentiation of the epidermis are known to involve the precise control of multiple signaling pathways. By contrast, little is known about the development of the mouse esophagus and forestomach, which are composed of a stratified squamous epithelium. Based on prior work in the skin, we hypothesized that bone morphogenetic protein (BMP) signaling is a central player. To test this hypothesis, we first used a BMP reporter mouse line harboring a BRE-lacZ allele, along with in situ hybridization to localize transcripts for BMP signaling components, including various antagonists. We then exploited a Shh-Cre allele that drives recombination in the embryonic foregut epithelium to generate gain- or loss-of-function models for the Bmpr1a (Alk3) receptor. In gain-of-function (Shh-Cre;Rosa26CAG-loxpstoploxp-caBmprIa) embryos, high levels of ectopic BMP signaling stall the transition from simple columnar to multilayered undifferentiated epithelium in the esophagus and forestomach. In loss-of-function experiments, conditional deletion of the BMP receptor in Shh-Cre;Bmpr1aflox/flox embryos allows the formation of a multilayered squamous epithelium but this fails to differentiate, as shown by the absence of expression of the suprabasal markers loricrin and involucrin. Together, these findings suggest multiple roles for BMP signaling in the developing esophagus and forestomach. PMID:21068065

802.11ac WLAN MIMO radio-over-fiber distributed antenna system for in-building networks based on multicore fiber

NASA Astrophysics Data System (ADS)

Morant, Maria; Llorente, Roberto

2017-01-01

In this work we propose and evaluate experimentally the performance of IEEE 802.11ac WLAN standard signals in radio-over-fiber (RoF) distributed-antenna systems based on multicore fiber (MCF) for in-building WLAN connectivity. The RoF performance of WLAN signals with different bandwidth is investigated considering up to IEEE 802.11ac maximum of 160 MHz per user. We evaluate experimentally the performance of WLAN signals employing different modulation and coding schemes achieving bitrates from 78 Mbps to 1404 Mbps per user in distances up to 300 m in a 4-core MCF. The performance of the wireless standard multiple-input multiple-output (MIMO) processing algorithms included in WLAN signals applied to the RoF transmission in MCF optical systems is also evaluated. The impact on the quality of the signal from one of the cores in the MIMO processing is investigated and compared with the results achieved with single-input single-output (SISO) transmission in each core. We measured the error vector magnitude (EVM) and the OFDM data burst information of the received WLAN signals after RoF transmission for different distributed-antenna systems with uni- and bi-directional MCF communication. Finally, we compare the received EVM of a single-antenna system (SISO arrangement) with WLAN systems using two antennas (2×2 MIMO) and four antennas (4×4 MIMO).

Extracellular Calcium Has Multiple Targets to Control Cell Proliferation.

PubMed

Capiod, Thierry

2016-01-01

Calcium channels and the two G-protein coupled receptors sensing extracellular calcium, calcium-sensing receptor (CaSR) and GPRC6a, are the two main means by which extracellular calcium can signal to cells and regulate many cellular processes including cell proliferation, migration and invasion of tumoral cells. Many intracellular signaling pathways are sensitive to cytosolic calcium rises and conversely intracellular signaling pathways can modulate calcium channel expression and activity. Calcium channels are undoubtedly involved in the former while the CaSR and GPRC6a are most likely to interfere with the latter. As for neurotransmitters, calcium ions use plasma membrane channels and GPCR to trigger cytosolic free calcium concentration rises and intracellular signaling and regulatory pathways activation. Calcium sensing GPCR, CaSR and GPRC6a, allow a supplemental degree of control and as for metabotropic receptors, they not only modulate calcium channel expression but they may also control calcium-dependent K+ channels. The multiplicity of intracellular signaling pathways involved, their sensitivity to local and global intracellular calcium increase and to CaSR and GPRC6a stimulation, the presence of membrane signalplex, all this confers the cells the plasticity they need to convert the effects of extracellular calcium into complex physiological responses and therefore determine their fate.

Notch signaling drives multiple myeloma induced osteoclastogenesis

PubMed Central

Colombo, Michela; Thümmler, Katja; Mirandola, Leonardo; Garavelli, Silvia; Todoerti, Katia; Apicella, Luana; Lazzari, Elisa; Lancellotti, Marialuigia; Platonova, Natalia; Akbar, Moeed; Chiriva-Internati, Maurizio; Soutar, Richard; Neri, Antonino; Goodyear, Carl S.; Chiaramonte, Raffaella

2014-01-01

Multiple myeloma (MM) is closely associated with bone destruction. Once migrated to the bone marrow, MM cells unbalance bone formation and resorption via the recruitment and maturation of osteoclast precursors. The Notch pathway plays a key role in different types of cancer and drives several biological processes relevant in MM, including cell localization within the bone marrow, proliferation, survival and pharmacological resistance. Here we present evidences that MM can efficiently drive osteoclastogenesis by contemporaneously activating Notch signaling on tumor cells and osteoclasts through the aberrant expression of Notch ligands belonging to the Jagged family. Active Notch signaling in MM cells induces the secretion of the key osteoclastogenic factor, RANKL, which can be boosted in the presence of stromal cells. In turn, MM cells-derived RANKL causes the upregulation of its receptor, RANK, and Notch2 in pre-osteoclasts. Notch2 stimulates osteoclast differentiation by promoting autocrine RANKL signaling. Finally, MM cells through Jagged ligands expression can also activate Notch signaling in pre-osteoclast by direct contact. Such synergism between tumor cells and pre-osteoclasts in MM-induced osteoclastogenesis can be disrupted by silencing tumor-derived Jagged1 and 2. These results make the Jagged ligands new promising therapeutic targets in MM to contrast bone disease and the associated co-morbidities. PMID:25257302

Stress peptide PACAP engages multiple signaling pathways within the carotid body to initiate excitatory responses in respiratory and sympathetic chemosensory afferents.

PubMed

Roy, Arijit; Derakhshan, Fatemeh; Wilson, Richard J A

2013-06-15

Consistent with a critical role in respiratory and autonomic stress responses, the carotid bodies are strongly excited by pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide implicated in stress responses throughout the sympathetic nervous system. PACAP excites isolated carotid body glomus cells via activation of PAC1 receptors, with one study suggesting PAC1-induced excitation is due entirely to protein kinase A (PKA)-mediated inhibition of TASK channels. However, in other systems, PAC1 is known to be coupled to multiple intracellular signaling pathways, including PKA, phospholipase C (PLC), phospholipase D (PLD), and protein kinase C (PKC), that trigger multiple downstream effectors including increased Ca²⁺ mobilization, inhibition of various K⁺ channels, and activation of nonselective cation channels. This study tests if non-PKA/TASK channel signaling helps mediate the stimulatory effects of PACAP on the carotid body. Using an ex vivo arterially perfused rat carotid body preparation, we show that PACAP-38 stimulates carotid sinus nerve activity in a biphasic manner (peak response, falling to plateau). PKA blocker H-89 only reduced the plateau response (~41%), whereas the TASK-1-like K⁺ channel blocker/transient receptor potential vanilloid 1 channel agonist anandamide only inhibited the peak response (~48%), suggesting involvement of additional pathways. The PLD blocker CAY10594 significantly inhibited both peak and plateau responses. The PLC blocker U73122 decimated both peak and plateau responses. Brefeldin A, a blocker of Epac (cAMP-activated guanine exchange factor, reported to link Gs-coupled receptors with PLC/PLD), also reduced both phases of the response, as did blocking signaling downstream of PLC/PLD with the PKC inhibitors chelerythrine chloride and GF109203X. Suggesting the involvement of non-TASK ion channels in the effects of PACAP, the A-type K⁺ channel blocker 4-aminopyridine, and the putative transient receptor potential channel (TRPC)/T-type calcium channel blocker SKF96365 each significantly inhibited the peak and steady-state responses. These data suggest the stimulatory effect of PACAP-38 on carotid body sensory activity is mediated through multiple signaling pathways: the PLC-PKC pathways predominates, with TRPC and/or T-type channel activation and Kv channel inactivation; only partial involvement is attributable to PKA and PLD activation.

Large-Signal Code TESLA: Current Status and Recent Development

DTIC Science & Technology

2008-04-01

K.Eppley, J.J.Petillo, “ High - power four cavity S - band multiple- beam klystron design”, IEEE Trans. Plasma Sci. , vol. 32, pp. 1119-1135, June 2004. 4...advances in the development of the large-signal code TESLA, mainly used for the modeling of high - power single- beam and multiple-beam klystron ...amplifiers. Keywords: large-signal code; multiple-beam klystrons ; serial and parallel versions. Introduction The optimization and design of new high power

Extraction of global 21-cm signal from simulated data for the Dark Ages Radio Explorer (DARE) using an MCMC pipeline

NASA Astrophysics Data System (ADS)

Tauscher, Keith A.; Burns, Jack O.; Rapetti, David; Mirocha, Jordan; Monsalve, Raul A.

2017-01-01

The Dark Ages Radio Explorer (DARE) is a mission concept proposed to NASA in which a crossed dipole antenna collects low frequency (40-120 MHz) radio measurements above the farside of the Moon to detect and characterize the global 21-cm signal from the early (z~35-11) Universe's neutral hydrogen. Simulated data for DARE includes: 1) the global signal modeled using the ares code, 2) spectrally smooth Galactic foregrounds with spatial structure taken from multiple radio foreground maps averaged over a large, well characterized beam, 3) systematics introduced in the data by antenna/receiver reflections, and 4) the Moon. This simulated data is fed into a signal extraction pipeline. As the signal is 4-5 orders of magnitude below the Galactic synchrotron contribution, it is best extracted from the data using Bayesian techniques which take full advantage of prior knowledge of the instrument and foregrounds. For the DARE pipeline, we use the affine-invariant MCMC algorithm implemented in the Python package, emcee. The pipeline also employs singular value decomposition to use known spectral features of the antenna and receiver to form a natural basis with which to fit instrumental systematics. Taking advantage of high-fidelity measurements of the antenna beam (to ~20 ppm) and precise calibration of the instrument, the pipeline extracts the global 21-cm signal with an average RMS error of 10-15 mK for multiple signal models.

Patterns of Ancestry, Signatures of Natural Selection, and Genetic Association with Stature in Western African Pygmies

PubMed Central

Jarvis, Joseph P.; Ferwerda, Bart; Froment, Alain; Bodo, Jean-Marie; Beggs, William; Hoffman, Gabriel; Mezey, Jason; Tishkoff, Sarah A.

2012-01-01

African Pygmy groups show a distinctive pattern of phenotypic variation, including short stature, which is thought to reflect past adaptation to a tropical environment. Here, we analyze Illumina 1M SNP array data in three Western Pygmy populations from Cameroon and three neighboring Bantu-speaking agricultural populations with whom they have admixed. We infer genome-wide ancestry, scan for signals of positive selection, and perform targeted genetic association with measured height variation. We identify multiple regions throughout the genome that may have played a role in adaptive evolution, many of which contain loci with roles in growth hormone, insulin, and insulin-like growth factor signaling pathways, as well as immunity and neuroendocrine signaling involved in reproduction and metabolism. The most striking results are found on chromosome 3, which harbors a cluster of selection and association signals between approximately 45 and 60 Mb. This region also includes the positional candidate genes DOCK3, which is known to be associated with height variation in Europeans, and CISH, a negative regulator of cytokine signaling known to inhibit growth hormone-stimulated STAT5 signaling. Finally, pathway analysis for genes near the strongest signals of association with height indicates enrichment for loci involved in insulin and insulin-like growth factor signaling. PMID:22570615

Optical frequency upconversion technique for transmission of wireless MIMO-type signals over optical fiber.

PubMed

Shaddad, R Q; Mohammad, A B; Al-Gailani, S A; Al-Hetar, A M

2014-01-01

The optical fiber is well adapted to pass multiple wireless signals having different carrier frequencies by using radio-over-fiber (ROF) technique. However, multiple wireless signals which have the same carrier frequency cannot propagate over a single optical fiber, such as wireless multi-input multi-output (MIMO) signals feeding multiple antennas in the fiber wireless (FiWi) system. A novel optical frequency upconversion (OFU) technique is proposed to solve this problem. In this paper, the novel OFU approach is used to transmit three wireless MIMO signals over a 20 km standard single mode fiber (SMF). The OFU technique exploits one optical source to produce multiple wavelengths by delivering it to a LiNbO3 external optical modulator. The wireless MIMO signals are then modulated by LiNbO3 optical intensity modulators separately using the generated optical carriers from the OFU process. These modulators use the optical single-sideband with carrier (OSSB+C) modulation scheme to optimize the system performance against the fiber dispersion effect. Each wireless MIMO signal is with a 2.4 GHz or 5 GHz carrier frequency, 1 Gb/s data rate, and 16-quadrature amplitude modulation (QAM). The crosstalk between the wireless MIMO signals is highly suppressed, since each wireless MIMO signal is carried on a specific optical wavelength.

Association of oxytocin receptor (OXTR) gene variants with multiple phenotype domains of autism spectrum disorder.

PubMed

Campbell, Daniel B; Datta, Dibyadeep; Jones, Shaine T; Batey Lee, Evon; Sutcliffe, James S; Hammock, Elizabeth A D; Levitt, Pat

2011-06-01

Autism spectrum disorder (ASD) is characterized by core deficits in social behavior, communication, and behavioral flexibility. Several lines of evidence indicate that oxytocin, signaling through its receptor (OXTR), is important in a wide range of social behaviors. In attempts to determine whether genetic variations in the oxytocin signaling system contribute to ASD susceptibility, seven recent reports indicated association of common genetic polymorphisms in the OXTR gene with ASD. Each involved relatively small sample sizes (57 to 436 families) and, where it was examined, failed to identify association of OXTR polymorphisms with measures of social behavior in individuals with ASD. We report genetic association analysis of 25 markers spanning the OXTR locus in 1,238 pedigrees including 2,333 individuals with ASD. Association of three markers previously implicated in ASD susceptibility, rs2268493 (P = 0.043), rs1042778 (P = 0.037), and rs7632287 (P = 0.016), was observed. Further, these genetic markers were associated with multiple core ASD phenotypes, including social domain dysfunction, measured by standardized instruments used to diagnose and describe ASD. The data suggest association of OXTR genetic polymorphisms with ASD, although the results should be interpreted with caution because none of the significant associations would survive appropriate correction for multiple comparisons. However, the current findings of association in a large independent cohort are consistent with previous results, and the biological plausibility of participation of the oxytocin signaling system in modulating social disruptions characteristic of ASD, suggest that functional polymorphisms of OXTR may contribute to ASD risk in a subset of families.

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

Harp, G. R.; Richards, Jon; Tarter, Jill C.

We report radio SETI observations on a large number of known exoplanets and other nearby star systems using the Allen Telescope Array (ATA). Observations were made over about 19000 hr from 2009 May to 2015 December. This search focused on narrowband radio signals from a set totaling 9293 stars, including 2015 exoplanet stars and Kepler objects of interest and an additional 65 whose planets may be close to their habitable zones. The ATA observations were made using multiple synthesized beams and an anticoincidence filter to help identify terrestrial radio interference. Stars were observed over frequencies from 1 to 9 GHzmore » in multiple bands that avoid strong terrestrial communication frequencies. Data were processed in near-real time for narrowband (0.7–100 Hz) continuous and pulsed signals with transmitter/receiver relative accelerations from −0.3 to 0.3 m s{sup −2}. A total of 1.9 × 10{sup 8} unique signals requiring immediate follow-up were detected in observations covering more than 8 × 10{sup 6} star-MHz. We detected no persistent signals from extraterrestrial technology exceeding our frequency-dependent sensitivity threshold of 180–310 × 10{sup −26} W m{sup −2}.« less

LISA Framework for Enhancing Gravitational Wave Signal Extraction Techniques

NASA Technical Reports Server (NTRS)

Thompson, David E.; Thirumalainambi, Rajkumar

2006-01-01

This paper describes the development of a Framework for benchmarking and comparing signal-extraction and noise-interference-removal methods that are applicable to interferometric Gravitational Wave detector systems. The primary use is towards comparing signal and noise extraction techniques at LISA frequencies from multiple (possibly confused) ,gravitational wave sources. The Framework includes extensive hybrid learning/classification algorithms, as well as post-processing regularization methods, and is based on a unique plug-and-play (component) architecture. Published methods for signal extraction and interference removal at LISA Frequencies are being encoded, as well as multiple source noise models, so that the stiffness of GW Sensitivity Space can be explored under each combination of methods. Furthermore, synthetic datasets and source models can be created and imported into the Framework, and specific degraded numerical experiments can be run to test the flexibility of the analysis methods. The Framework also supports use of full current LISA Testbeds, Synthetic data systems, and Simulators already in existence through plug-ins and wrappers, thus preserving those legacy codes and systems in tact. Because of the component-based architecture, all selected procedures can be registered or de-registered at run-time, and are completely reusable, reconfigurable, and modular.

Two-photon excited autofluorescence imaging of freshly isolated frog retinas.

PubMed

Lu, Rong-Wen; Li, Yi-Chao; Ye, Tong; Strang, Christianne; Keyser, Kent; Curcio, Christine A; Yao, Xin-Cheng

2011-06-01

The purpose of this study was to investigate cellular sources of autofluorescence signals in freshly isolated frog (Rana pipiens) retinas. Equipped with an ultrafast laser, a laser scanning two-photon excitation fluorescence microscope was employed for sub-cellular resolution examination of both sliced and flat-mounted retinas. Two-photon imaging of retinal slices revealed autofluorescence signals over multiple functional layers, including the photoreceptor layer (PRL), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL), and ganglion cell layer (GCL). Using flat-mounted retinas, depth-resolved imaging of individual retinal layers further confirmed multiple sources of autofluorescence signals. Cellular structures were clearly observed at the PRL, ONL, INL, and GCL. At the PRL, the autofluorescence was dominantly recorded from the intracellular compartment of the photoreceptors; while mixed intracellular and extracellular autofluorescence signals were observed at the ONL, INL, and GCL. High resolution autofluorescence imaging clearly revealed mosaic organization of rod and cone photoreceptors; and sub-cellular bright autofluorescence spots, which might relate to connecting cilium, was observed in the cone photoreceptors only. Moreover, single-cone and double-cone outer segments could be directly differentiated.

Bessel Fourier orientation reconstruction: an analytical EAP reconstruction using multiple shell acquisitions in diffusion MRI.

PubMed

Hosseinbor, Ameer Pasha; Chung, Moo K; Wu, Yu-Chien; Alexander, Andrew L

2011-01-01

The estimation of the ensemble average propagator (EAP) directly from q-space DWI signals is an open problem in diffusion MRI. Diffusion spectrum imaging (DSI) is one common technique to compute the EAP directly from the diffusion signal, but it is burdened by the large sampling required. Recently, several analytical EAP reconstruction schemes for multiple q-shell acquisitions have been proposed. One, in particular, is Diffusion Propagator Imaging (DPI) which is based on the Laplace's equation estimation of diffusion signal for each shell acquisition. Viewed intuitively in terms of the heat equation, the DPI solution is obtained when the heat distribution between temperatuere measurements at each shell is at steady state. We propose a generalized extension of DPI, Bessel Fourier Orientation Reconstruction (BFOR), whose solution is based on heat equation estimation of the diffusion signal for each shell acquisition. That is, the heat distribution between shell measurements is no longer at steady state. In addition to being analytical, the BFOR solution also includes an intrinsic exponential smootheing term. We illustrate the effectiveness of the proposed method by showing results on both synthetic and real MR datasets.

A Software Platform for Post-Processing Waveform-Based NDE

NASA Technical Reports Server (NTRS)

Roth, Donald J.; Martin, Richard E.; Seebo, Jeff P.; Trinh, Long B.; Walker, James L.; Winfree, William P.

2007-01-01

Ultrasonic, microwave, and terahertz nondestructive evaluation imaging systems generally require the acquisition of waveforms at each scan point to form an image. For such systems, signal and image processing methods are commonly needed to extract information from the waves and improve resolution of, and highlight, defects in the image. Since some similarity exists for all waveform-based NDE methods, it would seem a common software platform containing multiple signal and image processing techniques to process the waveforms and images makes sense where multiple techniques, scientists, engineers, and organizations are involved. This presentation describes NASA Glenn Research Center's approach in developing a common software platform for processing waveform-based NDE signals and images. This platform is currently in use at NASA Glenn and at Lockheed Martin Michoud Assembly Facility for processing of pulsed terahertz and ultrasonic data. Highlights of the software operation will be given. A case study will be shown for use with terahertz data. The authors also request scientists and engineers who are interested in sharing customized signal and image processing algorithms to contribute to this effort by letting the authors code up and include these algorithms in future releases.

Redox signaling in the cardiomyocyte: From physiology to failure.

PubMed

Santos, Celio X C; Raza, Sadaf; Shah, Ajay M

2016-05-01

The specific effect of oxygen and reactive oxygen species (ROS) in mediating post-translational modification of protein targets has emerged as a key mechanism regulating signaling components, a process termed redox signaling. ROS act in the post-translational modification of multiple target proteins including receptors, kinases, phosphatases, ion channels and transcription factors. Both O2 and ROS are major source of electrons in redox reactions in aerobic organisms. Because the heart has the highest O2 consumption among body organs, it is not surprising that redox signaling is central to heart function and pathophysiology. In this article, we review some of the main cardiac redox signaling pathways and their roles in the cardiomyocyte and in heart failure, with particular focus on the specific molecular targets of ROS in the heart. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Effects of Market Structure on Television News Pricing.

ERIC Educational Resources Information Center

Wirth, Michael O.; Wollert, James A.

Multiple regression techniques were used to examine the business side of local television news operations for November 1978. Research questions examined the effect of several variables on local television news prices (advertising rates), including type of ownership, network affiliation/signal type, market size, cable network penetration, market…

Simulation-based decision-making tool for adaptive traffic signal control on Tarrytown Road in the City of White Plains.

DOT National Transportation Integrated Search

2013-01-01

Transportation corridors are vital for our region and even the nations economy and quality of life. A corridor is usually a complicated system that may span multi-jurisdictions, contains multiple modes, include both freeways and local arterials, a...

Multiple chemosensory targets for discovery of novel chemicals for disruption of mosquito behavior

USDA-ARS?s Scientific Manuscript database

The yellow-fever mosquito Aedes aegypti is an important vector of diseases including dengue fever, yellow fever, chikungunya and West Nile virus. Olfactory and gustatory signals play important roles in the orientation of female mosquitoes to vertebrate hosts and initiation of blood feeding. Using re...

Mapping the functional versatility and fragility of Ras GTPase signaling circuits through in vitro network reconstitution

PubMed Central

Coyle, Scott M; Lim, Wendell A

2016-01-01

The Ras-superfamily GTPases are central controllers of cell proliferation and morphology. Ras signaling is mediated by a system of interacting molecules: upstream enzymes (GEF/GAP) regulate Ras’s ability to recruit multiple competing downstream effectors. We developed a multiplexed, multi-turnover assay for measuring the dynamic signaling behavior of in vitro reconstituted H-Ras signaling systems. By including both upstream regulators and downstream effectors, we can systematically map how different network configurations shape the dynamic system response. The concentration and identity of both upstream and downstream signaling components strongly impacted the timing, duration, shape, and amplitude of effector outputs. The distorted output of oncogenic alleles of Ras was highly dependent on the balance of positive (GAP) and negative (GEF) regulators in the system. We found that different effectors interpreted the same inputs with distinct output dynamics, enabling a Ras system to encode multiple unique temporal outputs in response to a single input. We also found that different Ras-to-GEF positive feedback mechanisms could reshape output dynamics in distinct ways, such as signal amplification or overshoot minimization. Mapping of the space of output behaviors accessible to Ras provides a design manual for programming Ras circuits, and reveals how these systems are readily adapted to produce an array of dynamic signaling behaviors. Nonetheless, this versatility comes with a trade-off of fragility, as there exist numerous paths to altered signaling behaviors that could cause disease. DOI: http://dx.doi.org/10.7554/eLife.12435.001 PMID:26765565

Stacked Transformer for Driver Gain and Receive Signal Splitting

NASA Technical Reports Server (NTRS)

Driscoll, Kevin R.

2013-01-01

In a high-speed signal transmission system that uses transformer coupling, there is a need to provide increased transmitted signal strength without adding active components. This invention uses additional transformers to achieve the needed gain. The prior art uses stronger drivers (which require an IC redesign and a higher power supply voltage), or the addition of another active component (which can decrease reliability, increase power consumption, reduce the beneficial effect of serializer/deserializer preemphasis or deemphasis, and/or interfere with fault containment mechanisms), or uses a different transformer winding ratio (which requires redesign of the transformer and may not be feasible with high-speed signals that require a 1:1 winding ratio). This invention achieves the required gain by connecting the secondaries of multiple transformers in series. The primaries of these transformers are currently either connected in parallel or are connected to multiple drivers. There is also a need to split a receive signal to multiple destinations with minimal signal loss. Additional transformers can achieve the split. The prior art uses impedance-matching series resistors that cause a loss of signal. Instead of causing a loss, most instantiations of this invention would actually provide gain. Multiple transformers are used instead of multiple windings on a single transformer because multiple windings on the same transformer would require a redesign of the transformer, and may not be feasible with high-speed transformers that usually require a bifilar winding with a 1:1 ratio. This invention creates the split by connecting the primaries of multiple transformers in series. The secondary of each transformer is connected to one of the intended destinations without the use of impedance-matching series resistors.

Mutations in the TGF-β Repressor SKI Cause Shprintzen-Goldberg Syndrome with Aortic Aneurysm

PubMed Central

Doyle, Alexander J.; Doyle, Jefferson J.; Bessling, Seneca L.; Maragh, Samantha; Lindsay, Mark E.; Schepers, Dorien; Gillis, Elisabeth; Mortier, Geert; Homfray, Tessa; Sauls, Kimberly; Norris, Russell A.; Huso, Nicholas D.; Leahy, Dan; Mohr, David W.; Caulfield, Mark J.; Scott, Alan F.; Destrée, Anne; Hennekam, Raoul C.; Arn, Pamela H.; Curry, Cynthia J.; Van Laer, Lut; McCallion, Andrew S.; Loeys, Bart L.; Dietz, Harry C.

2012-01-01

Increased transforming growth factor beta (TGF-β) signaling has been implicated in the pathogenesis of syndromic presentations of aortic aneurysm, including Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS)1-4. However, the location and character of many of the causal mutations in LDS would intuitively infer diminished TGF-β signaling5. Taken together, these data have engendered controversy regarding the specific role of TGF-β in disease pathogenesis. Shprintzen-Goldberg syndrome (SGS) has considerable phenotypic overlap with MFS and LDS, including aortic aneurysm6-8. We identified causative variation in 10 patients with SGS in the proto-oncogene SKI, a known repressor of TGF-β activity9,10. Cultured patient dermal fibroblasts showed enhanced activation of TGF-β signaling cascades and increased expression of TGF-β responsive genes. Morpholino-induced silencing of SKI paralogs in zebrafish recapitulated abnormalities seen in SGS patients. These data support the conclusion that increased TGF-β signaling is the mechanism underlying SGS and contributes to multiple syndromic presentations of aortic aneurysm. PMID:23023332

A chloroplast retrograde signal, 3'-phosphoadenosine 5'-phosphate, acts as a secondary messenger in abscisic acid signaling in stomatal closure and germination.

PubMed

Pornsiriwong, Wannarat; Estavillo, Gonzalo M; Chan, Kai Xun; Tee, Estee E; Ganguly, Diep; Crisp, Peter A; Phua, Su Yin; Zhao, Chenchen; Qiu, Jiaen; Park, Jiyoung; Yong, Miing Tiem; Nisar, Nazia; Yadav, Arun Kumar; Schwessinger, Benjamin; Rathjen, John; Cazzonelli, Christopher I; Wilson, Philippa B; Gilliham, Matthew; Chen, Zhong-Hua; Pogson, Barry J

2017-03-21

Organelle-nuclear retrograde signaling regulates gene expression, but its roles in specialized cells and integration with hormonal signaling remain enigmatic. Here we show that the SAL1-PAP (3'-phosphoadenosine 5'- phosphate) retrograde pathway interacts with abscisic acid (ABA) signaling to regulate stomatal closure and seed germination in Arabidopsis . Genetically or exogenously manipulating PAP bypasses the canonical signaling components ABA Insensitive 1 (ABI1) and Open Stomata 1 (OST1); priming an alternative pathway that restores ABA-responsive gene expression, ROS bursts, ion channel function, stomatal closure and drought tolerance in ost1 -2. PAP also inhibits wild type and abi1 -1 seed germination by enhancing ABA sensitivity. PAP-XRN signaling interacts with ABA, ROS and Ca 2+ ; up-regulating multiple ABA signaling components, including lowly-expressed Calcium Dependent Protein Kinases (CDPKs) capable of activating the anion channel SLAC1. Thus, PAP exhibits many secondary messenger attributes and exemplifies how retrograde signals can have broader roles in hormone signaling, allowing chloroplasts to fine-tune physiological responses.

The STAT3-Ser/Hes3 signaling axis: an emerging regulator of endogenous regeneration and cancer growth

PubMed Central

Poser, Steven W.; Park, Deric M.; Androutsellis-Theotokis, Andreas

2013-01-01

Stem cells, by definition, are able to both self-renew (give rise to more cells of their own kind) and demonstrate multipotential (the ability to differentiate into multiple cell types). To accommodate this unique dual ability, stem cells interpret signal transduction pathways in specialized ways. Notable examples include canonical and non-canonical branches of the Notch signaling pathway, with each controlling different downstream targets (e.g., Hes1 vs. Hes3) and promoting either differentiation or self-renewal. Similarly, stem cells utilize STAT3 signaling uniquely. Most mature cells studied thus far rely on tyrosine phosphorylation (STAT3-Tyr) to promote survival and growth; in contrast, STAT3-Tyr induces the differentiation of neural stem cells (NSCs). NSCs use an alternative phosphorylation site, STAT3-Ser, to regulate survival and growth, a site that is largely redundant for this function in most other cell types. STAT3-Ser regulates Hes3, and together they form a convergence point for several signals, including Notch, Tie2, and insulin receptor activation. Disregulation and manipulation of the STAT3-Ser/Hes3 signaling pathway is important in both tumorigenesis and regenerative medicine, and worthy of extensive study. PMID:24101906

Power control apparatus and methods for electric vehicles

DOEpatents

Gadh, Rajit; Chung, Ching-Yen; Chu, Chi-Cheng; Qiu, Li

2016-03-22

Electric vehicle (EV) charging apparatus and methods are described which allow the sharing of charge current between multiple vehicles connected to a single source of charging energy. In addition, this charge sharing can be performed in a grid-friendly manner by lowering current supplied to EVs when necessary in order to satisfy the needs of the grid, or building operator. The apparatus and methods can be integrated into charging stations or can be implemented with a middle-man approach in which a multiple EV charging box, which includes an EV emulator and multiple pilot signal generation circuits, is coupled to a single EV charge station.

Multiple velocity encoding in the phase of an MRI signal

NASA Astrophysics Data System (ADS)

Benitez-Read, E. E.

2017-01-01

The measurement of fluid velocity by encoding it in the phase of a magnetic resonance imaging (MRI) signal could allow the discrimination of the stationary spins signals from those of moving spins. This results in a wide variety of applications i.e. in medicine, in order to obtain more than angiograms, blood velocity images of veins, arteries and other vessels without having static tissue perturbing the signal of fluid in motion. The work presented in this paper is a theoretical analysis of some novel methods for multiple fluid velocity encoding in the phase of an MRI signal. These methods are based on a tripolar gradient (TPG) and can be an alternative to the conventional methods based on a bipolar gradient (BPG) and could be more suitable for multiple velocity encoding in the phase of an MRI signal.

Multiple frequency optical mixer and demultiplexer and apparatus for remote sensing

NASA Technical Reports Server (NTRS)

Chen, Jeffrey R. (Inventor)

2010-01-01

A pulsed laser system includes a modulator module configured to provide pulsed electrical signals and a plurality of solid-state seed sources coupled to the modulator module and configured to operate, responsive to the pulsed electrical signals, in a pulse mode. Each of the plurality of solid-state seed sources is tuned to a different frequency channel separated from any adjacent frequency channel by a frequency offset. The pulsed laser system also includes a combiner that combines outputs from each of the solid state seed sources into a single optical path and an optical doubler and demultiplexer coupled to the single optical path and providing each doubled seed frequency on a separate output path.

Method and Apparatus for Measuring Fluid Flow

NASA Technical Reports Server (NTRS)

Arndt, G. Dickey (Inventor); Nguyen, Thanh X. (Inventor); Carl, James R. (Inventor)

1997-01-01

Method and apparatus for making measurements on fluids related to their complex permeability are disclosed. A microwave probe is provided for exposure to the fluids. The probe can be non-intrusive or can also be positioned at the location where measurements are to be made. The impedance of the probe is determined. in part. by the complex dielectric constant of the fluids at the probe. A radio frequency signal is transmitted to the probe and the reflected signal is phase and amplitude detected at a rapid rate for the purpose of identifying the fluids. Multiple probes may be selectively positioned to monitor the behavior of the fluids including their flow rate. Fluids may be identified as between two or more different fluids as well as multiple phases of the same fluid based on differences between their complex permittivities.

Widespread GLI expression but limited canonical hedgehog signaling restricted to the ductular reaction in human chronic liver disease

PubMed Central

Tirnitz-Parker, Janina Elke Eleonore; Hamson, Elizabeth Jane; Warren, Alessandra; Maneck, Bharvi; Chen, Jinbiao; Patkunanathan, Bramilla; Boland, Jade; Cheng, Robert; Shackel, Nicholas Adam; Seth, Devanshi; Bowen, David Geoffrey; Martelotto, Luciano Gastón; Watkins, D. Neil; McCaughan, Geoffrey William

2017-01-01

Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations. This study extends these observations to human liver tissue, and analyses the effect of GLI inhibition on LPC viability/gene expression. Human donor and cirrhotic liver tissue specimens were evaluated for SHH, GLI2 and Pc expression using immunofluorescence and qRT-PCR. Changes to viability and gene expression in LPCs in vitro were assessed following GLI inhibition. Identification of Pc (as a marker of canonical Hh signaling) in human cirrhosis was predominantly confined to the ductular reaction and LPCs. In contrast, GLI2 was expressed in multiple cell populations including Pc-ve endothelium, hepatocytes, and leukocytes. HSCs/myofibroblasts (>99%) expressed GLI2, with only 1.92% displaying Pc. In vitro GLI signals maintained proliferation/viability within LPCs and GLI inhibition affected the expression of genes related to stemness, hepatocyte/biliary differentiation and Hh/Wnt signaling. At least two mechanisms of GLI signaling (Pc/SMO-dependent and Pc/SMO-independent) mediate chronic liver disease pathogenesis. This may have significant ramifications for the choice of Hh inhibitor (anti-SMO or anti-GLI) suitable for clinical trials. We also postulate GLI delivers a pro-survival signal to LPCs whilst maintaining stemness. PMID:28187190

Widespread GLI expression but limited canonical hedgehog signaling restricted to the ductular reaction in human chronic liver disease.

PubMed

Grzelak, Candice Alexandra; Sigglekow, Nicholas David; Tirnitz-Parker, Janina Elke Eleonore; Hamson, Elizabeth Jane; Warren, Alessandra; Maneck, Bharvi; Chen, Jinbiao; Patkunanathan, Bramilla; Boland, Jade; Cheng, Robert; Shackel, Nicholas Adam; Seth, Devanshi; Bowen, David Geoffrey; Martelotto, Luciano Gastón; Watkins, D Neil; McCaughan, Geoffrey William

2017-01-01

Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations. This study extends these observations to human liver tissue, and analyses the effect of GLI inhibition on LPC viability/gene expression. Human donor and cirrhotic liver tissue specimens were evaluated for SHH, GLI2 and Pc expression using immunofluorescence and qRT-PCR. Changes to viability and gene expression in LPCs in vitro were assessed following GLI inhibition. Identification of Pc (as a marker of canonical Hh signaling) in human cirrhosis was predominantly confined to the ductular reaction and LPCs. In contrast, GLI2 was expressed in multiple cell populations including Pc-ve endothelium, hepatocytes, and leukocytes. HSCs/myofibroblasts (>99%) expressed GLI2, with only 1.92% displaying Pc. In vitro GLI signals maintained proliferation/viability within LPCs and GLI inhibition affected the expression of genes related to stemness, hepatocyte/biliary differentiation and Hh/Wnt signaling. At least two mechanisms of GLI signaling (Pc/SMO-dependent and Pc/SMO-independent) mediate chronic liver disease pathogenesis. This may have significant ramifications for the choice of Hh inhibitor (anti-SMO or anti-GLI) suitable for clinical trials. We also postulate GLI delivers a pro-survival signal to LPCs whilst maintaining stemness.

Relevancies of multiple-interaction events and signal-to-noise ratio for Anger-logic based PET detector designs

NASA Astrophysics Data System (ADS)

Peng, Hao

2015-10-01

A fundamental challenge for PET block detector designs is to deploy finer crystal elements while limiting the number of readout channels. The standard Anger-logic scheme including light sharing (an 8 by 8 crystal array coupled to a 2×2 photodetector array with an optical diffuser, multiplexing ratio: 16:1) has been widely used to address such a challenge. Our work proposes a generalized model to study the impacts of two critical parameters on spatial resolution performance of a PET block detector: multiple interaction events and signal-to-noise ratio (SNR). The study consists of the following three parts: (1) studying light output profile and multiple interactions of 511 keV photons within crystal arrays of different crystal widths (from 4 mm down to 1 mm, constant height: 20 mm); (2) applying the Anger-logic positioning algorithm to investigate positioning/decoding uncertainties (i.e., "block effect") in terms of peak-to-valley ratio (PVR), with light sharing, multiple interactions and photodetector SNR taken into account; and (3) studying the dependency of spatial resolution on SNR in the context of modulation transfer function (MTF). The proposed model can be used to guide the development and evaluation of a standard Anger-logic based PET block detector including: (1) selecting/optimizing the configuration of crystal elements for a given photodetector SNR; and (2) predicting to what extent additional electronic multiplexing may be implemented to further reduce the number of readout channels.

EGFR Ligands Drive Multipotential Stromal Cells to Produce Multiple Growth Factors and Cytokines via Early Growth Response-1

PubMed Central

Kerpedjieva, Svetoslava S.; Kim, Duk Soo; Barbeau, Dominique J.

2012-01-01

Cell therapy with adult bone marrow multipotential stromal cells/mesenchymal stem cells (MSCs) presents a promising approach to promote wound healing and tissue regeneration. The strong paracrine capability of various growth factors and cytokines is a key mechanism of MSC-mediated wound healing and tissue regeneration, and the goal of this study is to understand the underlying mechanism that supports the strong paracrine machineries in MSCs. Microarray database analyses revealed that early growth response-1 (EGR1) is highly expressed in MSCs. Our previous studies showed that epidermal growth factor (EGF) treatment induces growth factor production in MSCs in vitro. Since EGF strongly upregulates EGR1, we hypothesized that EGF receptor (EGFR)–EGR1 signaling plays a pivotal role in MSC paracrine activity. EGF treatment upregulated the gene expression of growth factors and cytokines, including EGFR ligands in a protein kinase C (PKC)- and/or mitogen-activated protein kinase–extracellular-signal-regulated kinase-dependent manner, and it was reversed by shRNA against EGR1. PKC activator phorbol 12-myristate 13-acetate enhanced EGFR tyrosyl phosphorylation and upregulated the gene expression of growth factors and cytokines in a heparin-binding EGF-like growth factor (HBEGF) inhibitor CRM197 sensitive manner, indicating an involvement of autocrined HBEGF in the downstream of PKC signaling. Moreover, stimulation with growth factors and cytokines induced the expression of EGFR ligands, presumably via EGR1 upregulation. These data indicate EGR1 as a convergence point of multiple signaling pathways, which in turn augments the production of multiple growth factors and cytokines by enhancing the autocrine signaling with EGFR ligands. PMID:22316125

EGFR ligands drive multipotential stromal cells to produce multiple growth factors and cytokines via early growth response-1.

PubMed

Kerpedjieva, Svetoslava S; Kim, Duk Soo; Barbeau, Dominique J; Tamama, Kenichi

2012-09-01

Cell therapy with adult bone marrow multipotential stromal cells/mesenchymal stem cells (MSCs) presents a promising approach to promote wound healing and tissue regeneration. The strong paracrine capability of various growth factors and cytokines is a key mechanism of MSC-mediated wound healing and tissue regeneration, and the goal of this study is to understand the underlying mechanism that supports the strong paracrine machineries in MSCs. Microarray database analyses revealed that early growth response-1 (EGR1) is highly expressed in MSCs. Our previous studies showed that epidermal growth factor (EGF) treatment induces growth factor production in MSCs in vitro. Since EGF strongly upregulates EGR1, we hypothesized that EGF receptor (EGFR)-EGR1 signaling plays a pivotal role in MSC paracrine activity. EGF treatment upregulated the gene expression of growth factors and cytokines, including EGFR ligands in a protein kinase C (PKC)- and/or mitogen-activated protein kinase-extracellular-signal-regulated kinase-dependent manner, and it was reversed by shRNA against EGR1. PKC activator phorbol 12-myristate 13-acetate enhanced EGFR tyrosyl phosphorylation and upregulated the gene expression of growth factors and cytokines in a heparin-binding EGF-like growth factor (HBEGF) inhibitor CRM197 sensitive manner, indicating an involvement of autocrined HBEGF in the downstream of PKC signaling. Moreover, stimulation with growth factors and cytokines induced the expression of EGFR ligands, presumably via EGR1 upregulation. These data indicate EGR1 as a convergence point of multiple signaling pathways, which in turn augments the production of multiple growth factors and cytokines by enhancing the autocrine signaling with EGFR ligands.

Effects of multiple enzyme-substrate interactions in basic units of cellular signal processing

NASA Astrophysics Data System (ADS)

Seaton, D. D.; Krishnan, J.

2012-08-01

Covalent modification cycles are a ubiquitous feature of cellular signalling networks. In these systems, the interaction of an active enzyme with the unmodified form of its substrate is essential for signalling to occur. However, this interaction is not necessarily the only enzyme-substrate interaction possible. In this paper, we analyse the behaviour of a basic model of signalling in which additional, non-essential enzyme-substrate interactions are possible. These interactions include those between the inactive form of an enzyme and its substrate, and between the active form of an enzyme and its product. We find that these additional interactions can result in increased sensitivity and biphasic responses, respectively. The dynamics of the responses are also significantly altered by the presence of additional interactions. Finally, we evaluate the consequences of these interactions in two variations of our basic model, involving double modification of substrate and scaffold-mediated signalling, respectively. We conclude that the molecular details of protein-protein interactions are important in determining the signalling properties of enzymatic signalling pathways.

Lysophosphatidic Acid (LPA) Signaling in Human and Ruminant Reproductive Tract

PubMed Central

Wocławek-Potocka, Izabela; Rawińska, Paulina; Kowalczyk-Zieba, Ilona; Boruszewska, Dorota; Sinderewicz, Emilia; Waśniewski, Tomasz; Skarzynski, Dariusz Jan

2014-01-01

Lysophosphatidic acid (LPA) through activating its G protein-coupled receptors (LPAR 1–6) exerts diverse cellular effects that in turn influence several physiological processes including reproductive function of the female. Studies in various species of animals and also in humans have identified important roles for the receptor-mediated LPA signaling in multiple aspects of human and animal reproductive tract function. These aspects range from ovarian and uterine function, estrous cycle regulation, early embryo development, embryo implantation, decidualization to pregnancy maintenance and parturition. LPA signaling can also have pathological consequences, influencing aspects of endometriosis and reproductive tissue associated tumors. The review describes recent progress in LPA signaling research relevant to human and ruminant reproduction, pointing at the cow as a relevant model to study LPA influence on the human reproductive performance. PMID:24744506

MIMO nonlinear ultrasonic tomography by propagation and backpropagation method.

PubMed

Dong, Chengdong; Jin, Yuanwei

2013-03-01

This paper develops a fast ultrasonic tomographic imaging method in a multiple-input multiple-output (MIMO) configuration using the propagation and backpropagation (PBP) method. By this method, ultrasonic excitation signals from multiple sources are transmitted simultaneously to probe the objects immersed in the medium. The scattering signals are recorded by multiple receivers. Utilizing the nonlinear ultrasonic wave propagation equation and the received time domain scattered signals, the objects are to be reconstructed iteratively in three steps. First, the propagation step calculates the predicted acoustic potential data at the receivers using an initial guess. Second, the difference signal between the predicted value and the measured data is calculated. Third, the backpropagation step computes updated acoustical potential data by backpropagating the difference signal to the same medium computationally. Unlike the conventional PBP method for tomographic imaging where each source takes turns to excite the acoustical field until all the sources are used, the developed MIMO-PBP method achieves faster image reconstruction by utilizing multiple source simultaneous excitation. Furthermore, we develop an orthogonal waveform signaling method using a waveform delay scheme to reduce the impact of speckle patterns in the reconstructed images. By numerical experiments we demonstrate that the proposed MIMO-PBP tomographic imaging method results in faster convergence and achieves superior imaging quality.

Combined Cycle Engine Large-Scale Inlet for Mode Transition Experiments: System Identification Rack Hardware Design

NASA Technical Reports Server (NTRS)

Thomas, Randy; Stueber, Thomas J.

2013-01-01

The System Identification (SysID) Rack is a real-time hardware-in-the-loop data acquisition (DAQ) and control instrument rack that was designed and built to support inlet testing in the NASA Glenn Research Center 10- by 10-Foot Supersonic Wind Tunnel. This instrument rack is used to support experiments on the Combined-Cycle Engine Large-Scale Inlet for Mode Transition Experiment (CCE? LIMX). The CCE?LIMX is a testbed for an integrated dual flow-path inlet configuration with the two flow paths in an over-and-under arrangement such that the high-speed flow path is located below the lowspeed flow path. The CCE?LIMX includes multiple actuators that are designed to redirect airflow from one flow path to the other; this action is referred to as "inlet mode transition." Multiple phases of experiments have been planned to support research that investigates inlet mode transition: inlet characterization (Phase-1) and system identification (Phase-2). The SysID Rack hardware design met the following requirements to support Phase-1 and Phase-2 experiments: safely and effectively move multiple actuators individually or synchronously; sample and save effector control and position sensor feedback signals; automate control of actuator positioning based on a mode transition schedule; sample and save pressure sensor signals; and perform DAQ and control processes operating at 2.5 KHz. This document describes the hardware components used to build the SysID Rack including their function, specifications, and system interface. Furthermore, provided in this document are a SysID Rack effectors signal list (signal flow); system identification experiment setup; illustrations indicating a typical SysID Rack experiment; and a SysID Rack performance overview for Phase-1 and Phase-2 experiments. The SysID Rack described in this document was a useful tool to meet the project objectives.

Event-Driven Random-Access-Windowing CCD Imaging System

NASA Technical Reports Server (NTRS)

Monacos, Steve; Portillo, Angel; Ortiz, Gerardo; Alexander, James; Lam, Raymond; Liu, William

2004-01-01

A charge-coupled-device (CCD) based high-speed imaging system, called a realtime, event-driven (RARE) camera, is undergoing development. This camera is capable of readout from multiple subwindows [also known as regions of interest (ROIs)] within the CCD field of view. Both the sizes and the locations of the ROIs can be controlled in real time and can be changed at the camera frame rate. The predecessor of this camera was described in High-Frame-Rate CCD Camera Having Subwindow Capability (NPO- 30564) NASA Tech Briefs, Vol. 26, No. 12 (December 2002), page 26. The architecture of the prior camera requires tight coupling between camera control logic and an external host computer that provides commands for camera operation and processes pixels from the camera. This tight coupling limits the attainable frame rate and functionality of the camera. The design of the present camera loosens this coupling to increase the achievable frame rate and functionality. From a host computer perspective, the readout operation in the prior camera was defined on a per-line basis; in this camera, it is defined on a per-ROI basis. In addition, the camera includes internal timing circuitry. This combination of features enables real-time, event-driven operation for adaptive control of the camera. Hence, this camera is well suited for applications requiring autonomous control of multiple ROIs to track multiple targets moving throughout the CCD field of view. Additionally, by eliminating the need for control intervention by the host computer during the pixel readout, the present design reduces ROI-readout times to attain higher frame rates. This camera (see figure) includes an imager card consisting of a commercial CCD imager and two signal-processor chips. The imager card converts transistor/ transistor-logic (TTL)-level signals from a field programmable gate array (FPGA) controller card. These signals are transmitted to the imager card via a low-voltage differential signaling (LVDS) cable assembly. The FPGA controller card is connected to the host computer via a standard peripheral component interface (PCI).

Optical Frequency Upconversion Technique for Transmission of Wireless MIMO-Type Signals over Optical Fiber

PubMed Central

Shaddad, R. Q.; Mohammad, A. B.; Al-Gailani, S. A.; Al-Hetar, A. M.

2014-01-01

The optical fiber is well adapted to pass multiple wireless signals having different carrier frequencies by using radio-over-fiber (ROF) technique. However, multiple wireless signals which have the same carrier frequency cannot propagate over a single optical fiber, such as wireless multi-input multi-output (MIMO) signals feeding multiple antennas in the fiber wireless (FiWi) system. A novel optical frequency upconversion (OFU) technique is proposed to solve this problem. In this paper, the novel OFU approach is used to transmit three wireless MIMO signals over a 20 km standard single mode fiber (SMF). The OFU technique exploits one optical source to produce multiple wavelengths by delivering it to a LiNbO3 external optical modulator. The wireless MIMO signals are then modulated by LiNbO3 optical intensity modulators separately using the generated optical carriers from the OFU process. These modulators use the optical single-sideband with carrier (OSSB+C) modulation scheme to optimize the system performance against the fiber dispersion effect. Each wireless MIMO signal is with a 2.4 GHz or 5 GHz carrier frequency, 1 Gb/s data rate, and 16-quadrature amplitude modulation (QAM). The crosstalk between the wireless MIMO signals is highly suppressed, since each wireless MIMO signal is carried on a specific optical wavelength. PMID:24772009

Pulse transmission transceiver architecture for low power communications

DOEpatents

Dress, Jr., William B.; Smith, Stephen F.

2003-08-05

Systems and methods for pulse-transmission low-power communication modes are disclosed. A method of pulse transmission communications includes: generating a modulated pulse signal waveform; transforming said modulated pulse signal waveform into at least one higher-order derivative waveform; and transmitting said at least one higher-order derivative waveform as an emitted pulse. The systems and methods significantly reduce lower-frequency emissions from pulse transmission spread-spectrum communication modes, which reduces potentially harmful interference to existing radio frequency services and users and also simultaneously permit transmission of multiple data bits by utilizing specific pulse shapes.

Use of Mueller and non-Mueller matrices to describe polarization properties of telescope-based polarimeters

NASA Astrophysics Data System (ADS)

Seagraves, P. H.; Elmore, David F.

1994-09-01

Systems using optical elements such as linear polarizers, retarders, and mirrors can be represented by Mueller matrices. Some polarimeters include elements with time-varying polarization properties, multiple light beams, light detectors, and signal processing equipment. Standard Mueller matrix forms describing time-varying retarders, and beam splitters are presented, as well as non-Mueller matrices which describe detection and signal processing. These matrices provide a compact and intuitive mathematical description of polarimeter response which can aid in the refining of instrument designs.

EG-1 interacts with c-Src and activates its signaling pathway.

PubMed

Lu, Ming; Zhang, Liping; Sartippour, Maryam R; Norris, Andrew J; Brooks, Mai N

2006-10-01

EG-1 is significantly elevated in breast, colorectal, and prostate cancers. Overexpression of EG-1 stimulates cellular proliferation, and targeted inhibition blocks mouse xenograft tumor growth. To further clarify the function of EG-1, we investigated its role in c-Src activation. We observed that EG-1 overexpression results in activation of c-Src, but found no evidence that EG-1 is a direct Src substrate. EG-1 also binds to other members of the Src family. Furthermore, EG-1 shows interaction with multiple other SH3- and WW-containing molecules involved in various signaling pathways. These observations suggest that EG-1 may be involved in signaling pathways including c-Src activation.

Amorphous silicon radiation detectors

DOEpatents

Street, Robert A.; Perez-Mendez, Victor; Kaplan, Selig N.

1992-01-01

Hydrogenated amorphous silicon radiation detector devices having enhanced signal are disclosed. Specifically provided are transversely oriented electrode layers and layered detector configurations of amorphous silicon, the structure of which allow high electric fields upon application of a bias thereby beneficially resulting in a reduction in noise from contact injection and an increase in signal including avalanche multiplication and gain of the signal produced by incoming high energy radiation. These enhanced radiation sensitive devices can be used as measuring and detection means for visible light, low energy photons and high energy ionizing particles such as electrons, x-rays, alpha particles, beta particles and gamma radiation. Particular utility of the device is disclosed for precision powder crystallography and biological identification.

Amorphous silicon radiation detectors

DOEpatents

Street, R.A.; Perez-Mendez, V.; Kaplan, S.N.

1992-11-17

Hydrogenated amorphous silicon radiation detector devices having enhanced signal are disclosed. Specifically provided are transversely oriented electrode layers and layered detector configurations of amorphous silicon, the structure of which allow high electric fields upon application of a bias thereby beneficially resulting in a reduction in noise from contact injection and an increase in signal including avalanche multiplication and gain of the signal produced by incoming high energy radiation. These enhanced radiation sensitive devices can be used as measuring and detection means for visible light, low energy photons and high energy ionizing particles such as electrons, x-rays, alpha particles, beta particles and gamma radiation. Particular utility of the device is disclosed for precision powder crystallography and biological identification. 13 figs.

Working With LGBT Baby Boomers and Older Adults: Factors That Signal a Welcoming Service Environment.

PubMed

Croghan, Catherine F; Moone, Rajean P; Olson, Andrea M

2015-01-01

Many providers recognize the importance of creating culturally competent services for lesbian, gay, bisexual, and transgender (LGBT) older adults. Although multiple resources list steps to make professional practices more LGBT-welcoming, these resources provide no empirical data to support their recommendations. LGBT older adults (N = 327) were asked to describe what signals that a provider is LGBT-welcoming. Six of the top 10 signals related to provider behavior and suggest the importance of staff training; the balance included display of signage and rainbow flags, use of inclusive language on forms and the presence of LGBT-identified staff. Results provide evidence-based recommendations for working with LGBT older adults.

Apparatus and Methods for Photoacoustic Measurement of Light Absorption of Particulate and Gaseous Species

NASA Technical Reports Server (NTRS)

Brown, William (Inventor); Yu, Zhenhong (Inventor); Kebabian, Paul L. (Inventor); Assif, James (Inventor)

2017-01-01

In one embodiment, a photoacoustic effect measurement instrument for measuring a species (e.g., a species of PM) in a gas employs a pair of differential acoustic cells including a sample cell that receives sample gas including the species, and a reference cell that receives a filtered version of the sample gas from which the species has been substantially removed. An excitation light source provides an amplitude modulated beam to each of the acoustic cells. An array of multiple microphones is mounted to each of the differential acoustic cells, and measures an acoustic wave generated in the respective acoustic cell by absorption of light by sample gas therein to produce a respective signal. The microphones are isolated from sample gas internal to the acoustic cell by a film. A preamplifier determines a differential signal and a controller calculates concentration of the species based on the differential signal.

Neuroendocrine regulation of somatic growth in fishes.

PubMed

Dai, XiangYan; Zhang, Wei; Zhuo, ZiJian; He, JiangYan; Yin, Zhan

2015-02-01

Growth is a polygenic trait that is under the influence of multiple physiological pathways regulating energy metabolism and muscle growth. Among the possible growth-regulating pathways in vertebrates, components of the somatotropic axis are thought to have the greatest influence. There is growing body of literature focusing on the somatotropic axis and its role regulating growth in fish. This includes research into growth hormone, upstream hypothalamic hormones, insulin-like growth factors, and downstream signaling molecules. Many of these signals have both somatic effects stimulating the growth of tissues and metabolic effects that play a role in nutrient metabolism. Signals of other endocrine axes exhibit profound effects on the function of the somatotropic axis in vivo. In this review we highlight recent advances in our understanding of the teleost fish endocrine somatotropic axis, including emerging research using genetic modified models. These studies have revealed new aspects and challenges associated with regulation of the important steps of somatic growth.

Minimal requirement for induction of natural cytotoxicity and intersection of activation signals by inhibitory receptors.

PubMed

Bryceson, Yenan T; Ljunggren, Hans-Gustaf; Long, Eric O

2009-09-24

Natural killer (NK) cells provide innate control of infected and neoplastic cells. Multiple receptors have been implicated in natural cytotoxicity, but their individual contribution remains unclear. Here, we studied the activation of primary, resting human NK cells by Drosophila cells expressing ligands for receptors NKG2D, DNAM-1, 2B4, CD2, and LFA-1. Each receptor was capable of inducing inside-out signals for LFA-1, promoting adhesion, but none induced degranulation. Rather, release of cytolytic granules required synergistic activation through coengagement of receptors, shown here for NKG2D and 2B4. Although engagement of NKG2D and 2B4 was not sufficient for strong target cell lysis, collective engagement of LFA-1, NKG2D, and 2B4 defined a minimal requirement for natural cytotoxicity. Remarkably, inside-out signaling induced by each one of these receptors, including LFA-1, was inhibited by receptor CD94/NKG2A binding to HLA-E. Strong inside-out signals induced by the combination of NKG2D and 2B4 or by CD16 could overcome CD94/NKG2A inhibition. In contrast, degranulation induced by these receptors was still subject to inhibition by CD94/NKG2A. These results reveal multiple layers in the activation pathway for natural cytotoxicity and that steps as distinct as inside-out signaling to LFA-1 and signals for granule release are sensitive to inhibition by CD94/NKG2A.

Novel applications of trophic factors, Wnt and WISP for neuronal repair and regeneration in metabolic disease

PubMed Central

Maiese, Kenneth

2015-01-01

Diabetes mellitus affects almost 350 million individuals throughout the globe resulting in significant morbidity and mortality. Of further concern is the growing population of individuals that remain undiagnosed but are susceptible to the detrimental outcomes of this disorder. Diabetes mellitus leads to multiple complications in the central and peripheral nervous systems that include cognitive impairment, retinal disease, neuropsychiatric disease, cerebral ischemia, and peripheral nerve degeneration. Although multiple strategies are being considered, novel targeting of trophic factors, Wnt signaling, Wnt1 inducible signaling pathway protein 1, and stem cell tissue regeneration are considered to be exciting prospects to overcome the cellular mechanisms that lead to neuronal injury in diabetes mellitus involving oxidative stress, apoptosis, and autophagy. Pathways that involve insulin-like growth factor-1, fibroblast growth factor, epidermal growth factor, and erythropoietin can govern glucose homeostasis and are intimately tied to Wnt signaling that involves Wnt1 and Wnt1 inducible signaling pathway protein 1 (CCN4) to foster control over stem cell proliferation, wound repair, cognitive decline, β-cell proliferation, vascular regeneration, and programmed cell death. Ultimately, cellular metabolism through Wnt signaling is driven by primary metabolic pathways of the mechanistic target of rapamycin and AMP activated protein kinase. These pathways offer precise biological control of cellular metabolism, but are exquisitely sensitive to the different components of Wnt signaling. As a result, unexpected clinical outcomes can ensue and therefore demand careful translation of the mechanisms that govern neural repair and regeneration in diabetes mellitus. PMID:26170801

Somatostatin signaling and the regulation of growth and metabolism in fish.

PubMed

Klein, Sarah E; Sheridan, Mark A

2008-05-14

The study of the somatostatins (SS) signaling system in fish has provided important information about the structure, function, and evolution of SSs and their receptors. The SS signaling system elicits widespread biological actions via multiple hormone variants, numerous receptor subtypes, and a variety of signal transduction pathways. SSs alter growth via both direct and indirect actions, including inhibiting growth hormone release at the pituitary, decreasing hepatic GH sensitivity, and lowering plasma IGF-I levels. Metabolism also is significantly influenced by SSs. SSs stimulate the breakdown of energy stores and influences digestion, food intake, nutrient absorption, and food conversion both directly and through the modulation of other hormonal systems. The study of fish, which display a diversity of habitat types and life history forms, reveals that the SS signaling system helps regulate energy partitioning and integrate metabolism with growth and other biological processes.

Molecular Signaling in Tumorigenesis of Gastric Cancer

PubMed

Molaei, Fatemeh; Forghanifard, Mohammad Mahdi; Fahim, Yasaman; Abbaszadegan, Mohammad Reza

2018-07-01

Gastric cancer (GC) is regarded as the fifth most common cancer and the third cause of cancer-related deaths worldwide. Mechanism of GC pathogenesis is still unclear and relies on multiple factors, including environmental and genetic characteristics. One of the most important environmental factors of GC occurrence is infection with Helicobacter pylori that is classified as class one carcinogens. Dysregulation of several genes and pathways play an essential role during gastric carcinogenesis. Dysregulation of developmental pathways such as Wnt/β-catenin signaling, Hedgehog signaling, Hippo pathway, Notch signaling, nuclear factor-kB, and epidermal growth factor receptor have been found in GC. Epithelial-mesenchymal transition, as an important process during embryogenesis and tumorigenesis, is supposed to play a role in initiation, invasion, metastasis, and progression of GC. Although surgery is the main therapeutic modality of the disease, the understanding of biological processes of cell signaling pathways may help to develop new therapeutic targets for GC.

Parallel Implementation of the Wideband DOA Algorithm on the IBM Cell BE Processor

DTIC Science & Technology

2010-05-01

Abstract—The Multiple Signal Classification ( MUSIC ) algorithm is a powerful technique for determining the Direction of Arrival (DOA) of signals...Broadband Engine Processor (Cell BE). The process of adapting the serial based MUSIC algorithm to the Cell BE will be analyzed in terms of parallelism and...using Multiple Signal Classification MUSIC algorithm [4] • Computation of Focus matrix • Computation of number of sources • Separation of Signal

Robust myoelectric signal detection based on stochastic resonance using multiple-surface-electrode array made of carbon nanotube composite paper

NASA Astrophysics Data System (ADS)

Shirata, Kento; Inden, Yuki; Kasai, Seiya; Oya, Takahide; Hagiwara, Yosuke; Kaeriyama, Shunichi; Nakamura, Hideyuki

2016-04-01

We investigated the robust detection of surface electromyogram (EMG) signals based on the stochastic resonance (SR) phenomenon, in which the response to weak signals is optimized by adding noise, combined with multiple surface electrodes. Flexible carbon nanotube composite paper (CNT-cp) was applied to the surface electrode, which showed good performance that is comparable to that of conventional Ag/AgCl electrodes. The SR-based EMG signal system integrating an 8-Schmitt-trigger network and the multiple-CNT-cp-electrode array successfully detected weak EMG signals even when the subject’s body is in the motion, which was difficult to achieve using the conventional technique. The feasibility of the SR-based EMG detection technique was confirmed by demonstrating its applicability to robot hand control.

Alleviating Autonomic Dysreflexia after Spinal Cord Injury

DTIC Science & Technology

2017-12-01

autonomic disorders greatly influence the functional, psychological , and socioeconomic aspects of patients’ lives. Compared to numer- ous...The disruption of descending autonomic pathways renders abnormalities in multiple organ systems including cardiovascular function, respiration...the rise in blood pressure, the integration center in the brainstem transmits signals to the heart via parasympathetic pathways to reduce the heart

Identification and Classification of Orthogonal Frequency Division Multiple Access (OFDMA) Signals Used in Next Generation Wireless Systems

DTIC Science & Technology

2012-03-01

advanced antenna systems AMC adaptive modulation and coding AWGN additive white Gaussian noise BPSK binary phase shift keying BS base station BTC ...QAM-16, and QAM-64, and coding types include convolutional coding (CC), convolutional turbo coding (CTC), block turbo coding ( BTC ), zero-terminating

Screening the ToxCast Phase I, II, and e1K Chemical Libraries for Inhibition of Deiodinase Type 1,2 and 3 Enzyme Activity

EPA Science Inventory

Thyroid hormone (TH) signaling and homeostasis is dependent upon coordination of multiple key events including thyroidal iodide uptake and hormone synthesis, and peripheral metabolism and elimination. Deiodinase enzymes play an essential role in converting the pro-hormone thyroxi...

Generating nonlinear FM chirp radar signals by multiple integrations

DOEpatents

Doerry, Armin W [Albuquerque, NM

2011-02-01

A phase component of a nonlinear frequency modulated (NLFM) chirp radar pulse can be produced by performing digital integration operations over a time interval defined by the pulse width. Each digital integration operation includes applying to a respectively corresponding input parameter value a respectively corresponding number of instances of digital integration.

Resolvin D1 Increases Mucin Secretion in Cultured Rat Conjunctival Goblet Cells via Multiple Signaling Pathways

PubMed Central

Lippestad, Marit; Hodges, Robin R.; Utheim, Tor P.; Serhan, Charles N.; Dartt, Darlene A.

2017-01-01

Purpose Goblet cells in the conjunctiva secrete mucin into the tear film protecting the ocular surface. The proresolution mediator resolvin D1 (RvD1) regulates mucin secretion to maintain homeostasis during physiological conditions and in addition, actively terminates inflammation. We determined the signaling mechanisms used by RvD1 in cultured rat conjunctival goblet cells to increase intracellular [Ca2+] ([Ca2+]i) and induce glycoconjugate secretion. Methods Increase in [Ca2+]i were measured using fura 2/AM and glycoconjugate secretion determined using an enzyme-linked lectin assay with the lectin Ulex Europaeus Agglutinin 1. Signaling pathways activated by RvD1 were studied after goblet cells were pretreated with signaling pathway inhibitors before stimulation with RvD1. The results were compared with results when goblet cells were stimulated with RvD1 alone and percent inhibition calculated. Results The increase in [Ca2+]i stimulated by RvD1 was blocked by inhibitors to phospholipases (PL-) -D, -C, -A2, protein kinase C (PKC), extracellular signal-regulated kinases (ERK)1/2 and Ca2+/calmodulin-dependent kinase (Ca2+/CamK). Glycoconjugate secretion was significantly inhibited by PLD, -C, -A2, ERK1/2 and Ca2+/CamK, but not PKC. Conclusions We conclude that RvD1 increases glycoconjugate secretion from goblet cells via multiple signaling pathways including PLC, PLD, and PLA2, as well as their signaling components ERK1/2 and Ca2+/CamK to preserve the mucous layer and maintain homeostasis by protecting the eye from desiccating stress, allergens, and pathogens. PMID:28892824

Signal Processing Methods for Liquid Rocket Engine Combustion Stability Assessments

NASA Technical Reports Server (NTRS)

Kenny, R. Jeremy; Lee, Erik; Hulka, James R.; Casiano, Matthew

2011-01-01

The J2X Gas Generator engine design specifications include dynamic, spontaneous, and broadband combustion stability requirements. These requirements are verified empirically based high frequency chamber pressure measurements and analyses. Dynamic stability is determined with the dynamic pressure response due to an artificial perturbation of the combustion chamber pressure (bomb testing), and spontaneous and broadband stability are determined from the dynamic pressure responses during steady operation starting at specified power levels. J2X Workhorse Gas Generator testing included bomb tests with multiple hardware configurations and operating conditions, including a configuration used explicitly for engine verification test series. This work covers signal processing techniques developed at Marshall Space Flight Center (MSFC) to help assess engine design stability requirements. Dynamic stability assessments were performed following both the CPIA 655 guidelines and a MSFC in-house developed statistical-based approach. The statistical approach was developed to better verify when the dynamic pressure amplitudes corresponding to a particular frequency returned back to pre-bomb characteristics. This was accomplished by first determining the statistical characteristics of the pre-bomb dynamic levels. The pre-bomb statistical characterization provided 95% coverage bounds; these bounds were used as a quantitative measure to determine when the post-bomb signal returned to pre-bomb conditions. The time for post-bomb levels to acceptably return to pre-bomb levels was compared to the dominant frequency-dependent time recommended by CPIA 655. Results for multiple test configurations, including stable and unstable configurations, were reviewed. Spontaneous stability was assessed using two processes: 1) characterization of the ratio of the peak response amplitudes to the excited chamber acoustic mode amplitudes and 2) characterization of the variability of the peak response's frequency over the test duration. This characterization process assists in evaluating the discreteness of a signal as well as the stability of the chamber response. Broadband stability was assessed using a running root-mean-square evaluation. These techniques were also employed, in a comparative analysis, on available Fastrac data, and these results are presented here.

Curcumin inhibits cancer progression through regulating expression of microRNAs.

PubMed

Zhou, Siying; Zhang, Sijie; Shen, Hongyu; Chen, Wei; Xu, Hanzi; Chen, Xiu; Sun, Dawei; Zhong, Shanliang; Zhao, Jianhua; Tang, Jinhai

2017-02-01

Curcumin, a major yellow pigment and spice in turmeric and curry, is a powerful anti-cancer agent. The anti-tumor activities of curcumin include inhibition of tumor proliferation, angiogenesis, invasion and metastasis, induction of tumor apoptosis, increase of chemotherapy sensitivity, and regulation of cell cycle and cancer stem cell, indicating that curcumin maybe a strong therapeutic potential through modulating various cancer progression. It has been reported that microRNAs as small noncoding RNA molecules are related to cancer progression, which can be regulated by curcumin. Dysregulated microRNAs play vital roles in tumor biology via regulating expressions of target genes and then influencing multiple cancer-related signaling pathways. In this review, we focused on the inhibition effect of curcumin on various cancer progression by regulating expression of multiple microRNAs. Curcumin-induced dysregulation of microRNAs may activate or inactivate a set of signaling pathways, such as Akt, Bcl-2, PTEN, p53, Notch, and Erbb signaling pathways. A better understanding of the relation between curcumin and microRNAs may provide a potential therapeutic target for various cancers.

Space-division-multiplexed transmission of 3x3 multiple-input multiple-output wireless signals over conventional graded-index multimode fiber.

PubMed

Lei, Yi; Li, Jianqiang; Fan, Yuting; Yu, Dawei; Fu, Songnian; Yin, Feifei; Dai, Yitang; Xu, Kun

2016-12-12

In this paper, we experimentally demonstrate space-division-multiplexed (SDM) transmission of IEEE 802.11ac-compliant 3-spatial-stream WLAN signals over 3 spatial modes of conventional 50um graded-index (GI) multimode fiber (MMF) employing non-mode-selective 3D-waveguide photonic lantern. Two kinds of scenarios, including fiber-only transmission and fiber-wireless hybrid transmission, were investigated by measuring error vector magnitude (EVM) performance for each stream and condition number (CN) of the channel matrix. The experimental results show that, SDM-based MMF link could offer a CN< 20dB well-conditioned MIMO channel over up to 1km fiber length within 0-6GHz, achieving as low as 2.38%, 2.97% and 2.11% EVM performance for 1km MMF link at 2.4GHz, 5.8GHz, and 200m MMF link followed by 1m air distance at 2.7GHz, respectively. These results indicate the possibility to distribute wireless MIMO signals over existing in-building commercially-available MMFs with enormous cost-saving.

Bench-to-bedside review: Angiopoietin signalling in critical illness – a future target?

PubMed Central

van Meurs, Matijs; Kümpers, Philipp; Ligtenberg, Jack JM; Meertens, John HJM; Molema, Grietje; Zijlstra, Jan G

2009-01-01

Multiple organ dysfunction syndrome (MODS) occurs in response to major insults such as sepsis, severe haemorrhage, trauma, major surgery and pancreatitis. The mortality rate is high despite intensive supportive care. The pathophysiological mechanism underlying MODS are not entirely clear, although several have been proposed. Overwhelming inflammation, immunoparesis, occult oxygen debt and other mechanisms have been investigated, and – despite many unanswered questions – therapies targeting these mechanisms have been developed. Unfortunately, only a few interventions, usually those targeting multiple mechanisms at the same time, have appeared to be beneficial. We clearly need to understand better the mechanisms that underlie MODS. The endothelium certainly plays an active role in MODS. It functions at the intersection of several systems, including inflammation, coagulation, haemodynamics, fluid and electrolyte balance, and cell migration. An important regulator of these systems is the angiopoietin/Tie2 signalling system. In this review we describe this signalling system, giving special attention to what is known about it in critically ill patients and its potential as a target for therapy. PMID:19435476

Strigolactone regulates shoot development through a core signalling pathway

PubMed Central

Müller, Dörte

2016-01-01

ABSTRACT Strigolactones are a recently identified class of hormone that regulate multiple aspects of plant development. The DWARF14 (D14) α/β fold protein has been identified as a strigolactone receptor, which can act through the SCFMAX2 ubiquitin ligase, but the universality of this mechanism is not clear. Multiple proteins have been suggested as targets for strigolactone signalling, including both direct proteolytic targets of SCFMAX2, and downstream targets. However, the relevance and importance of these proteins to strigolactone signalling in many cases has not been fully established. Here we assess the contribution of these targets to strigolactone signalling in adult shoot developmental responses. We find that all examined strigolactone responses are regulated by SCFMAX2 and D14, and not by other D14-like proteins. We further show that all examined strigolactone responses likely depend on degradation of SMXL proteins in the SMXL6 clade, and not on the other proposed proteolytic targets BES1 or DELLAs. Taken together, our results suggest that in the adult shoot, the dominant mode of strigolactone signalling is D14-initiated, MAX2-mediated degradation of SMXL6-related proteins. We confirm that the BRANCHED1 transcription factor and the PIN-FORMED1 auxin efflux carrier are plausible downstream targets of this pathway in the regulation of shoot branching, and show that BRC1 likely acts in parallel to PIN1. PMID:27793831

Demonstration of Space Optical Transmitter Development for Multiple High Frequency Bands

NASA Technical Reports Server (NTRS)

Nguyen, Hung; Simons, Rainee; Wintucky, Edwin; Freeman, Jon

2013-01-01

As the demand for multiple radio frequency carrier bands continues to grow in space communication systems, the design of a cost-effective compact optical transmitter that is capable of transmitting selective multiple RF bands is of great interest, particularly for NASA Space Communications Network Programs. This paper presents experimental results that demonstrate the feasibility of a concept based on an optical wavelength division multiplexing (WDM) technique that enables multiple microwave bands with different modulation formats and bandwidths to be combined and transmitted all in one unit, resulting in many benefits to space communication systems including reduced size, weight and complexity with corresponding savings in cost. Experimental results will be presented including the individual received RF signal power spectra for the L, C, X, Ku, Ka, and Q frequency bands, and measurements of the phase noise associated with each RF frequency. Also to be presented is a swept RF frequency power spectrum showing simultaneous multiple RF frequency bands transmission. The RF frequency bands in this experiment are among those most commonly used in NASA space environment communications.

Multiple cis-acting signals, some weak by necessity, collectively direct robust transport of oskar mRNA to the oocyte.

PubMed

Ryu, Young Hee; Kenny, Andrew; Gim, Youme; Snee, Mark; Macdonald, Paul M

2017-09-15

Localization of mRNAs can involve multiple steps, each with its own cis -acting localization signals and transport factors. How is the transition between different steps orchestrated? We show that the initial step in localization of Drosophila oskar mRNA - transport from nurse cells to the oocyte - relies on multiple cis -acting signals. Some of these are binding sites for the translational control factor Bruno, suggesting that Bruno plays an additional role in mRNA transport. Although transport of oskar mRNA is essential and robust, the localization activity of individual transport signals is weak. Notably, increasing the strength of individual transport signals, or adding a strong transport signal, disrupts the later stages of oskar mRNA localization. We propose that the oskar transport signals are weak by necessity; their weakness facilitates transfer of the oskar mRNA from the oocyte transport machinery to the machinery for posterior localization. © 2017. Published by The Company of Biologists Ltd.

Emodin inhibits coxsackievirus B3 replication via multiple signalling cascades leading to suppression of translation.

PubMed

Zhang, Huifang M; Wang, Fengping; Qiu, Ye; Ye, Xin; Hanson, Paul; Shen, Hongxing; Yang, Decheng

2016-02-15

CVB3 (coxsackievirus 3) is a primary causal agent of viral myocarditis. Emodin is a natural compound isolated from certain plant roots. In the present study, we found that emodin inhibited CVB3 replication in vitro and in mice, and now we report an unrecognized mechanism by which emodin inhibits CVB3 replication through suppression of viral protein translation via multiple pathways. On one hand, emodin treatment inhibited Akt/mTOR (mammalian target of rapamycin) signalling and activated 4EBP1 (eukaryotic initiation factor 4R-binding protein 1), leading to suppression of translation initiation of ribosomal protein L32 encoded by a 5'-TOP (terminal oligopyrimidine) mRNA. On the other hand, emodin treatment differentially regulated multiple signal cascades, including Akt/mTORC1/p70(S6K) (p70 S6 kinase), ERK1/2 (extracellular-signal-regulated kinase 1/2)/p90(RSK) (p90 ribosomal S6 kinase) and Ca(2+)/calmodulin, leading to activation of eEF2K (eukaryotic elongation factor 2 kinase) and subsequent inactivation of eEF2 (eukaryotic elongation factor 2), resulting in inhibition of CVB3 VP1 (viral protein 1) synthesis. These data imply that eEF2K is a major factor mediating cross-talk of different arms of signalling cascades in this signal network. This notion was verified by either overexpressing eEF2K or treating the cells with siRNAs or eEF2K inhibitor A484954. We showed further that the emodin-induced decrease in p70(S6K) phosphorylation plays a dominant positive role in activation of eEF2K and in turn in conferring the antiviral effect of emodin. This finding was further solidified by expressing constitutively active and dominant-negative Akt. Collectively, our data reveal that emodin inhibits viral replication through impairing translational machinery and suppression of viral translation elongation. © 2016 Authors; published by Portland Press Limited.

Extracting fingerprint of wireless devices based on phase noise and multiple level wavelet decomposition

NASA Astrophysics Data System (ADS)

Zhao, Weichen; Sun, Zhuo; Kong, Song

2016-10-01

Wireless devices can be identified by the fingerprint extracted from the signal transmitted, which is useful in wireless communication security and other fields. This paper presents a method that extracts fingerprint based on phase noise of signal and multiple level wavelet decomposition. The phase of signal will be extracted first and then decomposed by multiple level wavelet decomposition. The statistic value of each wavelet coefficient vector is utilized for constructing fingerprint. Besides, the relationship between wavelet decomposition level and recognition accuracy is simulated. And advertised decomposition level is revealed as well. Compared with previous methods, our method is simpler and the accuracy of recognition remains high when Signal Noise Ratio (SNR) is low.

Triple-Quantum Filtered NMR Imaging of Sodium -23 in the Human Brain

NASA Astrophysics Data System (ADS)

Keltner, John Robinson

In the past multiple-quantum filtered imaging of biexponential relaxation sodium-23 nuclei in the human brain has been limited by low signal to noise ratios; this thesis demonstrates that such imaging is feasible when using a modified gradient-selected triple-quantum filter at a repetition time which maximizes the signal to noise ratio. Nuclear magnetic resonance imaging of biexponential relaxation sodium-23 (^{23}Na) nuclei in the human brain may be useful for detecting ischemia, cancer, and pathophysiology related to manic-depression. Multiple -quantum filters may be used to selectively image biexponential relaxation ^{23}Na signals since these filters suppress single-exponential relaxation ^{23}Na signals. In this thesis, the typical repetition times (200 -300 ms) used for in vivo multiple-quantum filtered ^{23}Na experiments are shown to be approximately 5 times greater than the optimal repetition time which maximizes multiple-quantum filtered SNR. Calculations and experimental verification show that the gradient-selected triple-quantum (GS3Q) filtered SNR for ^ {23}Na in a 4% agarose gel increases by a factor of two as the repetition time decreases from 300 ms to 55 ms. It is observed that a simple reduction of repetition time also increases spurious single-quantum signals from GS3Q filtered experiments. Irreducible superoperator calculations have been used to design a modified GS3Q filter which more effectively suppresses the spurious single-quantum signals. The modified GS3Q filter includes a preparatory crusher gradient and two-step-phase cycling. Using the modified GS3Q filter and a repetition time of 70 ms, a three dimensional triple-quantum filtered image of a phantom modelling ^{23} Na in the brain was obtained. The phantom consisted of two 4 cm diameter spheres inside of a 8.5 cm x 7 cm ellipsoid. The two spheres contained 0.012 and 0.024 M ^{23}Na in 4% agarose gel. Surrounding the spheres and inside the ellipsoid was 0.03 M aqueous ^{23}Na. The image dimensions were 16 x 16 x 16 voxels with the dimension of a voxel being 1.5 x 1.5 x 1.5 cm^3. The signal to noise ratio for the GS3Q filtered ^ {23}Na signal from the 0.012 and 0.024 M ^{23}Na spheres was 17 and 30 for a 54 minute experiment at 2.35 T. (Abstract shortened by UMI.).

A new adaptive algorithm for automated feature extraction in exponentially damped signals for health monitoring of smart structures

NASA Astrophysics Data System (ADS)

Qarib, Hossein; Adeli, Hojjat

2015-12-01

In this paper authors introduce a new adaptive signal processing technique for feature extraction and parameter estimation in noisy exponentially damped signals. The iterative 3-stage method is based on the adroit integration of the strengths of parametric and nonparametric methods such as multiple signal categorization, matrix pencil, and empirical mode decomposition algorithms. The first stage is a new adaptive filtration or noise removal scheme. The second stage is a hybrid parametric-nonparametric signal parameter estimation technique based on an output-only system identification technique. The third stage is optimization of estimated parameters using a combination of the primal-dual path-following interior point algorithm and genetic algorithm. The methodology is evaluated using a synthetic signal and a signal obtained experimentally from transverse vibrations of a steel cantilever beam. The method is successful in estimating the frequencies accurately. Further, it estimates the damping exponents. The proposed adaptive filtration method does not include any frequency domain manipulation. Consequently, the time domain signal is not affected as a result of frequency domain and inverse transformations.

Methylation and microRNA-mediated epigenetic regulation of SOCS3

PubMed Central

Boosani, Chandra S.; Agrawal, Devendra K.

2017-01-01

Epigenetic gene silencing of several genes causes different pathological conditions in humans, and DNA methylation has been identified as one of the key mechanisms that underlie this evolutionarily conserved phenomenon associated with developmental and pathological gene regulation. Recent advances in the miRNA technology with high throughput analysis of gene regulation further increased our understanding on the role of miRNAs regulating multiple gene expression. There is increasing evidence supporting that the miRNAs not only regulate gene expression but they also are involved in the hypermethylation of promoter sequences, which cumulatively contributes to the epigenetic gene silencing. Here, we critically evaluated the recent progress on the transcriptional regulation of an important suppressor protein that inhibits cytokine-mediated signaling, SOCS3, whose expression is directly regulated both by promoter methylation and also by microRNAs, affecting its vital cell regulating functions. SOCS3 was identified as a potent inhibitor of Jak/STAT signaling pathway which is frequently upregulated in several pathologies, including cardiovascular disease, cancer, diabetes, viral infections, and the expression of SOCS3 was inhibited or greatly reduced due to hypermethylation of the CpG islands in its promoter region or suppression of its expression by different microRNAs. Additionally, we discuss key intracellular signaling pathways regulated by SOCS3 involving cellular events, including cell proliferation, cell growth, cell migration and apoptosis. Identification of the pathway intermediates as specific targets would not only aid in the development of novel therapeutic drugs, but, would also assist in developing new treatment strategies that could successfully be employed in combination therapy to target multiple signaling pathways. PMID:25682267

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

PubMed

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

2014-12-12

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

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

PubMed Central

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

2014-01-01

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

Selective tyrosine kinase inhibition by imatinib mesylate for the treatment of autoimmune arthritis

PubMed Central

Paniagua, Ricardo T.; Sharpe, Orr; Ho, Peggy P.; Chan, Steven M.; Chang, Anna; Higgins, John P.; Tomooka, Beren H.; Thomas, Fiona M.; Song, Jason J.; Goodman, Stuart B.; Lee, David M.; Genovese, Mark C.; Utz, Paul J.; Steinman, Lawrence; Robinson, William H.

2006-01-01

Tyrosine kinases play a central role in the activation of signal transduction pathways and cellular responses that mediate the pathogenesis of rheumatoid arthritis. Imatinib mesylate (imatinib) is a tyrosine kinase inhibitor developed to treat Bcr/Abl-expressing leukemias and subsequently found to treat c-Kit–expressing gastrointestinal stromal tumors. We demonstrate that imatinib potently prevents and treats murine collagen-induced arthritis (CIA). We further show that micromolar concentrations of imatinib abrogate multiple signal transduction pathways implicated in RA pathogenesis, including mast cell c-Kit signaling and TNF-α release, macrophage c-Fms activation and cytokine production, and fibroblast PDGFR signaling and proliferation. In our studies, imatinib attenuated PDGFR signaling in fibroblast-like synoviocytes (FLSs) and TNF-α production in synovial fluid mononuclear cells (SFMCs) derived from human RA patients. Imatinib-mediated inhibition of a spectrum of signal transduction pathways and the downstream pathogenic cellular responses may provide a powerful approach to treat RA and other inflammatory diseases. PMID:16981009

Role of FGF/FGFR signaling in skeletal development and homeostasis: learning from mouse models

PubMed Central

Su, Nan; Jin, Min; Chen, Lin

2014-01-01

Fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling plays essential roles in bone development and diseases. Missense mutations in FGFs and FGFRs in humans can cause various congenital bone diseases, including chondrodysplasia syndromes, craniosynostosis syndromes and syndromes with dysregulated phosphate metabolism. FGF/FGFR signaling is also an important pathway involved in the maintenance of adult bone homeostasis. Multiple kinds of mouse models, mimicking human skeleton diseases caused by missense mutations in FGFs and FGFRs, have been established by knock-in/out and transgenic technologies. These genetically modified mice provide good models for studying the role of FGF/FGFR signaling in skeleton development and homeostasis. In this review, we summarize the mouse models of FGF signaling-related skeleton diseases and recent progresses regarding the molecular mechanisms, underlying the role of FGFs/FGFRs in the regulation of bone development and homeostasis. This review also provides a perspective view on future works to explore the roles of FGF signaling in skeletal development and homeostasis. PMID:26273516

Cystic fibrosis transmembrane conductance regulator-emerging regulator of cancer.

PubMed

Zhang, Jieting; Wang, Yan; Jiang, Xiaohua; Chan, Hsiao Chang

2018-05-01

Mutations of cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis, the most common life-limiting recessive genetic disease among Caucasians. CFTR mutations have also been linked to increased risk of various cancers but remained controversial for a long time. Recent studies have begun to reveal that CFTR is not merely an ion channel but also an important regulator of cancer development and progression with multiple signaling pathways identified. In this review, we will first present clinical findings showing the correlation of genetic mutations or aberrant expression of CFTR with cancer incidence in multiple cancers. We will then focus on the roles of CFTR in fundamental cellular processes including transformation, survival, proliferation, migration, invasion and epithelial-mesenchymal transition in cancer cells, highlighting the signaling pathways involved. Finally, the association of CFTR expression levels with patient prognosis, and the potential of CFTR as a cancer prognosis indicator in human malignancies will be discussed.

Device design and signal processing for multiple-input multiple-output multimode fiber links

NASA Astrophysics Data System (ADS)

Appaiah, Kumar; Vishwanath, Sriram; Bank, Seth R.

2012-01-01

Multimode fibers (MMFs) are limited in data rate capabilities owing to modal dispersion. However, their large core diameter simplifies alignment and packaging, and makes them attractive for short and medium length links. Recent research has shown that the use of signal processing and techniques such as multiple-input multiple-output (MIMO) can greatly improve the data rate capabilities of multimode fibers. In this paper, we review recent experimental work using MIMO and signal processing for multimode fibers, and the improvements in data rates achievable with these techniques. We then present models to design as well as simulate the performance benefits obtainable with arrays of lasers and detectors in conjunction with MIMO, using channel capacity as the metric to optimize. We also discuss some aspects related to complexity of the algorithms needed for signal processing and discuss techniques for low complexity implementation.

Expression of multiple sexual signals by fathers and sons in the East-Mediterranean barn swallow: are advertising strategies heritable?

PubMed

Vortman, Yoni; Safran, Rebecca J; Reiner Brodetzki, Tali; Dor, Roi; Lotem, Arnon

2015-01-01

The level of expression of sexually selected traits is generally determined by genes, environment and their interaction. In species that use multiple sexual signals which may be costly to produce, investing in the expression of one sexual signal may limit the expression of the other, favoring the evolution of a strategy for resource allocation among signals. As a result, even when the expression of sexual signals is condition dependent, the relative level of expression of each signal may be heritable. We tested this hypothesis in the East-Mediterranean barn swallow (Hirundo rustica transitiva), in which males have been shown to express two uncorrelated sexual signals: red-brown ventral coloration, and long tail streamers. We show that variation in both signals may partially be explained by age, as well as by paternal origin (genetic father-son regressions), but that the strongest similarity between fathers and sons is the relative allocation towards one trait or the other (relative expression index), rather than the expression of the traits themselves. These results suggest that the expression of one signal is not independent of the other, and that genetic strategies for resource allocation among sexual signals may be selected for during the evolution of multiple sexual signals.

Expression of Multiple Sexual Signals by Fathers and Sons in the East-Mediterranean Barn Swallow: Are Advertising Strategies Heritable?

PubMed Central

Vortman, Yoni; Safran, Rebecca J.; Reiner Brodetzki, Tali; Dor, Roi; Lotem, Arnon

2015-01-01

The level of expression of sexually selected traits is generally determined by genes, environment and their interaction. In species that use multiple sexual signals which may be costly to produce, investing in the expression of one sexual signal may limit the expression of the other, favoring the evolution of a strategy for resource allocation among signals. As a result, even when the expression of sexual signals is condition dependent, the relative level of expression of each signal may be heritable. We tested this hypothesis in the East-Mediterranean barn swallow (Hirundo rustica transitiva), in which males have been shown to express two uncorrelated sexual signals: red-brown ventral coloration, and long tail streamers. We show that variation in both signals may partially be explained by age, as well as by paternal origin (genetic father-son regressions), but that the strongest similarity between fathers and sons is the relative allocation towards one trait or the other (relative expression index), rather than the expression of the traits themselves. These results suggest that the expression of one signal is not independent of the other, and that genetic strategies for resource allocation among sexual signals may be selected for during the evolution of multiple sexual signals. PMID:25679206

Genetic insights into the mechanisms of Fgf signaling

PubMed Central

Brewer, J. Richard; Mazot, Pierre; Soriano, Philippe

2016-01-01

The fibroblast growth factor (Fgf) family of ligands and receptor tyrosine kinases is required throughout embryonic and postnatal development and also regulates multiple homeostatic functions in the adult. Aberrant Fgf signaling causes many congenital disorders and underlies multiple forms of cancer. Understanding the mechanisms that govern Fgf signaling is therefore important to appreciate many aspects of Fgf biology and disease. Here we review the mechanisms of Fgf signaling by focusing on genetic strategies that enable in vivo analysis. These studies support an important role for Erk1/2 as a mediator of Fgf signaling in many biological processes but have also provided strong evidence for additional signaling pathways in transmitting Fgf signaling in vivo. PMID:27036966

Vismodegib hedgehog-signaling inhibition and treatment of basal cell carcinomas as well as keratocystic odontogenic tumors in Gorlin syndrome.

PubMed

Booms, Patrick; Harth, Marc; Sader, Robert; Ghanaati, Shahram

2015-01-01

Vismodegib hedgehog signaling inhibition treatment has potential for reducing the burden of multiple skin basal cell carcinomas and jaw keratocystic odontogenic tumors. They are major criteria for the diagnosis of Gorlin syndrome, also called nevoid basal cell carcinoma syndrome. Clinical features of Gorlin syndrome are reported, and the relevance of hedgehog signaling pathway inhibition by oral vismodegib for maxillofacial surgeons is highlighted. In summary, progressed basal cell carcinoma lesions are virtually inoperable. Keratocystic odontogenic tumors have an aggressive behavior including rapid growth and extension into adjacent tissues. Interestingly, nearly complete regression of multiple Gorlin syndrome-associated keratocystic odontogenic tumors following treatment with vismodegib. Due to radio-hypersensitivity in Gorlin syndrome, avoidance of treatment by radiotherapy is strongly recommended for all affected individuals. Vismodegib can help in those instances where radiation is contra-indicated, or the lesions are inoperable. The effect of vismodegib on basal cell carcinomas was associated with a significant decrease in hedgehog-signaling and tumor proliferation. Vismodegib, a new and approved drug for the treatment of advanced basal cell carcinoma, is a specific oncogene inhibitor. It also seems to be effective for treatment of keratocystic odontogenic tumors and basal cell carcinomas in Gorlin syndrome, rendering the surgical resections less challenging.

Estimation of the quantification uncertainty from flow injection and liquid chromatography transient signals in inductively coupled plasma mass spectrometry

NASA Astrophysics Data System (ADS)

Laborda, Francisco; Medrano, Jesús; Castillo, Juan R.

2004-06-01

The quality of the quantitative results obtained from transient signals in high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS) and flow injection-inductively coupled plasma mass spectrometry (FI-ICPMS) was investigated under multielement conditions. Quantification methods were based on multiple-point calibration by simple and weighted linear regression, and double-point calibration (measurement of the baseline and one standard). An uncertainty model, which includes the main sources of uncertainty from FI-ICPMS and HPLC-ICPMS (signal measurement, sample flow rate and injection volume), was developed to estimate peak area uncertainties and statistical weights used in weighted linear regression. The behaviour of the ICPMS instrument was characterized in order to be considered in the model, concluding that the instrument works as a concentration detector when it is used to monitorize transient signals from flow injection or chromatographic separations. Proper quantification by the three calibration methods was achieved when compared to reference materials, although the double-point calibration allowed to obtain results of the same quality as the multiple-point calibration, shortening the calibration time. Relative expanded uncertainties ranged from 10-20% for concentrations around the LOQ to 5% for concentrations higher than 100 times the LOQ.

Characterization of electrically-active defects in ultraviolet light-emitting diodes with laser-based failure analysis techniques

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

Miller, Mary A.; Tangyunyong, Paiboon; Cole, Edward I.

2016-01-14

Laser-based failure analysis techniques demonstrate the ability to quickly and non-intrusively screen deep ultraviolet light-emitting diodes (LEDs) for electrically-active defects. In particular, two laser-based techniques, light-induced voltage alteration and thermally-induced voltage alteration, generate applied voltage maps (AVMs) that provide information on electrically-active defect behavior including turn-on bias, density, and spatial location. Here, multiple commercial LEDs were examined and found to have dark defect signals in the AVM indicating a site of reduced resistance or leakage through the diode. The existence of the dark defect signals in the AVM correlates strongly with an increased forward-bias leakage current. This increased leakage ismore » not present in devices without AVM signals. Transmission electron microscopy analysis of a dark defect signal site revealed a dislocation cluster through the pn junction. The cluster included an open core dislocation. Even though LEDs with few dark AVM defect signals did not correlate strongly with power loss, direct association between increased open core dislocation densities and reduced LED device performance has been presented elsewhere [M. W. Moseley et al., J. Appl. Phys. 117, 095301 (2015)].« less

Characterization of electrically-active defects in ultraviolet light-emitting diodes with laser-based failure analysis techniques

DOE PAGES

Miller, Mary A.; Tangyunyong, Paiboon; Edward I. Cole, Jr.

2016-01-12

In this study, laser-based failure analysis techniques demonstrate the ability to quickly and non-intrusively screen deep ultraviolet light-emitting diodes(LEDs) for electrically-active defects. In particular, two laser-based techniques, light-induced voltage alteration and thermally-induced voltage alteration, generate applied voltage maps (AVMs) that provide information on electrically-active defect behavior including turn-on bias, density, and spatial location. Here, multiple commercial LEDs were examined and found to have dark defect signals in the AVM indicating a site of reduced resistance or leakage through the diode. The existence of the dark defect signals in the AVM correlates strongly with an increased forward-bias leakage current. This increasedmore » leakage is not present in devices without AVM signals. Transmission electron microscopyanalysis of a dark defect signal site revealed a dislocation cluster through the pn junction. The cluster included an open core dislocation. Even though LEDs with few dark AVM defect signals did not correlate strongly with power loss, direct association between increased open core dislocation densities and reduced LED device performance has been presented elsewhere [M. W. Moseley et al., J. Appl. Phys. 117, 095301 (2015)].« less

SUMOylation of ATRIP potentiates DNA damage signaling by boosting multiple protein interactions in the ATR pathway

PubMed Central

Wu, Ching-Shyi; Ouyang, Jian; Mori, Eiichiro; Nguyen, Hai Dang; Maréchal, Alexandre; Hallet, Alexander; Chen, David J.; Zou, Lee

2014-01-01

The ATR (ATM [ataxia telangiectasia-mutated]- and Rad3-related) checkpoint is a crucial DNA damage signaling pathway. While the ATR pathway is known to transmit DNA damage signals through the ATR–Chk1 kinase cascade, whether post-translational modifications other than phosphorylation are important for this pathway remains largely unknown. Here, we show that protein SUMOylation plays a key role in the ATR pathway. ATRIP, the regulatory partner of ATR, is modified by SUMO2/3 at K234 and K289. An ATRIP mutant lacking the SUMOylation sites fails to localize to DNA damage and support ATR activation efficiently. Surprisingly, the ATRIP SUMOylation mutant is compromised in the interaction with a protein group, rather than a single protein, in the ATR pathway. Multiple ATRIP-interacting proteins, including ATR, RPA70, TopBP1, and the MRE11–RAD50–NBS1 complex, exhibit reduced binding to the ATRIP SUMOylation mutant in cells and display affinity for SUMO2 chains in vitro, suggesting that they bind not only ATRIP but also SUMO. Fusion of a SUMO2 chain to the ATRIP SUMOylation mutant enhances its interaction with the protein group and partially suppresses its localization and functional defects, revealing that ATRIP SUMOylation promotes ATR activation by providing a unique type of protein glue that boosts multiple protein interactions along the ATR pathway. PMID:24990965

Target-responsive DNA hydrogel mediated "stop-flow" microfluidic paper-based analytic device for rapid, portable and visual detection of multiple targets.

PubMed

Wei, Xiaofeng; Tian, Tian; Jia, Shasha; Zhu, Zhi; Ma, Yanli; Sun, Jianjun; Lin, Zhenyu; Yang, Chaoyong James

2015-04-21

A versatile point-of-care assay platform was developed for simultaneous detection of multiple targets based on a microfluidic paper-based analytic device (μPAD) using a target-responsive hydrogel to mediate fluidic flow and signal readout. An aptamer-cross-linked hydrogel was used as a target-responsive flow regulator in the μPAD. In the absence of a target, the hydrogel is formed in the flow channel, stopping the flow in the μPAD and preventing the colored indicator from traveling to the final observation spot, thus yielding a "signal off" readout. In contrast, in the presence of a target, no hydrogel is formed because of the preferential interaction of target and aptamer. This allows free fluidic flow in the μPAD, carrying the indicator to the observation spot and producing a "signal on" readout. The device is inexpensive to fabricate, easy to use, and disposable after detection. Testing results can be obtained within 6 min by the naked eye via a simple loading operation without the need for any auxiliary equipment. Multiple targets, including cocaine, adenosine, and Pb(2+), can be detected simultaneously, even in complex biological matrices such as urine. The reported method offers simple, low cost, rapid, user-friendly, point-of-care testing, which will be useful in many applications.

Dynamic changes in global microRNAome and transcriptome reveal complex miRNA-mRNA regulated host response to Japanese Encephalitis Virus in microglial cells

PubMed Central

Kumari, Bharti; Jain, Pratistha; Das, Shaoli; Ghosal, Suman; Hazra, Bibhabasu; Trivedi, Ashish Chandra; Basu, Anirban; Chakrabarti, Jayprokas; Vrati, Sudhanshu; Banerjee, Arup

2016-01-01

Microglia cells in the brain play essential role during Japanese Encephalitis Virus (JEV) infection and may lead to change in microRNA (miRNA) and mRNA profile. These changes may together control disease outcome. Using Affymetrix microarray platform, we profiled cellular miRNA and mRNA expression at multiple time points during viral infection in human microglial (CHME3) cells. In silico analysis of microarray data revealed a phased pattern of miRNAs expression, associated with JEV replication and provided unique signatures of infection. Target prediction and pathway enrichment analysis identified anti correlation between differentially expressed miRNA and the gene expression at multiple time point which ultimately affected diverse signaling pathways including Notch signaling pathways in microglia. Activation of Notch pathway during JEV infection was demonstrated in vitro and in vivo. The expression of a subset of miRNAs that target multiple genes in Notch signaling pathways were suppressed and their overexpression could affect JEV induced immune response. Further analysis provided evidence for the possible presence of cellular competing endogenous RNA (ceRNA) associated with innate immune response. Collectively, our data provide a uniquely comprehensive view of the changes in the host miRNAs induced by JEV during cellular infection and identify Notch pathway in modulating microglia mediated inflammation. PMID:26838068

Dynamic changes in global microRNAome and transcriptome reveal complex miRNA-mRNA regulated host response to Japanese Encephalitis Virus in microglial cells.

PubMed

Kumari, Bharti; Jain, Pratistha; Das, Shaoli; Ghosal, Suman; Hazra, Bibhabasu; Trivedi, Ashish Chandra; Basu, Anirban; Chakrabarti, Jayprokas; Vrati, Sudhanshu; Banerjee, Arup

2016-02-03

Microglia cells in the brain play essential role during Japanese Encephalitis Virus (JEV) infection and may lead to change in microRNA (miRNA) and mRNA profile. These changes may together control disease outcome. Using Affymetrix microarray platform, we profiled cellular miRNA and mRNA expression at multiple time points during viral infection in human microglial (CHME3) cells. In silico analysis of microarray data revealed a phased pattern of miRNAs expression, associated with JEV replication and provided unique signatures of infection. Target prediction and pathway enrichment analysis identified anti correlation between differentially expressed miRNA and the gene expression at multiple time point which ultimately affected diverse signaling pathways including Notch signaling pathways in microglia. Activation of Notch pathway during JEV infection was demonstrated in vitro and in vivo. The expression of a subset of miRNAs that target multiple genes in Notch signaling pathways were suppressed and their overexpression could affect JEV induced immune response. Further analysis provided evidence for the possible presence of cellular competing endogenous RNA (ceRNA) associated with innate immune response. Collectively, our data provide a uniquely comprehensive view of the changes in the host miRNAs induced by JEV during cellular infection and identify Notch pathway in modulating microglia mediated inflammation.

Optimal sampling and quantization of synthetic aperture radar signals

NASA Technical Reports Server (NTRS)

Wu, C.

1978-01-01

Some theoretical and experimental results on optimal sampling and quantization of synthetic aperture radar (SAR) signals are presented. It includes a description of a derived theoretical relationship between the pixel signal to noise ratio of processed SAR images and the number of quantization bits per sampled signal, assuming homogeneous extended targets. With this relationship known, a solution may be realized for the problem of optimal allocation of a fixed data bit-volume (for specified surface area and resolution criterion) between the number of samples and the number of bits per sample. The results indicate that to achieve the best possible image quality for a fixed bit rate and a given resolution criterion, one should quantize individual samples coarsely and thereby maximize the number of multiple looks. The theoretical results are then compared with simulation results obtained by processing aircraft SAR data.

Calcium/calmodulin-mediated signal network in plants

NASA Technical Reports Server (NTRS)

Yang, Tianbao; Poovaiah, B. W.

2003-01-01

Various extracellular stimuli elicit specific calcium signatures that can be recognized by different calcium sensors. Calmodulin, the predominant calcium receptor, is one of the best-characterized calcium sensors in eukaryotes. In recent years, completion of the Arabidopsis genome project and advances in functional genomics have helped to identify and characterize numerous calmodulin-binding proteins in plants. There are some similarities in Ca(2+)/calmodulin-mediated signaling in plants and animals. However, plants possess multiple calmodulin genes and many calmodulin target proteins, including unique protein kinases and transcription factors. Some of these proteins are likely to act as "hubs" during calcium signal transduction. Hence, a better understanding of the function of these calmodulin target proteins should help in deciphering the Ca(2+)/calmodulin-mediated signal network and its role in plant growth, development and response to environmental stimuli.

Stress signaling pathways for the pathogenicity of Cryptococcus.

PubMed

Bahn, Yong-Sun; Jung, Kwang-Woo

2013-12-01

Sensing, responding, and adapting to the surrounding environment are crucial for all living organisms to survive, proliferate, and differentiate in their biological niches. This ability is also essential for Cryptococcus neoformans and its sibling species Cryptococcus gattii, as these pathogens have saprobic and parasitic life cycles in natural and animal host environments. The ability of Cryptococcus to cause fatal meningoencephalitis is highly related to its capability to remodel and optimize its metabolic and physiological status according to external cues. These cues act through multiple stress signaling pathways through a panoply of signaling components, including receptors/sensors, small GTPases, secondary messengers, kinases, transcription factors, and other miscellaneous adaptors or regulators. In this minireview, we summarize and highlight the importance of several stress signaling pathways that influence the pathogenicity of Cryptococcus and discuss future challenges in these areas.

Stress Signaling Pathways for the Pathogenicity of Cryptococcus

PubMed Central

Jung, Kwang-Woo

2013-01-01

Sensing, responding, and adapting to the surrounding environment are crucial for all living organisms to survive, proliferate, and differentiate in their biological niches. This ability is also essential for Cryptococcus neoformans and its sibling species Cryptococcus gattii, as these pathogens have saprobic and parasitic life cycles in natural and animal host environments. The ability of Cryptococcus to cause fatal meningoencephalitis is highly related to its capability to remodel and optimize its metabolic and physiological status according to external cues. These cues act through multiple stress signaling pathways through a panoply of signaling components, including receptors/sensors, small GTPases, secondary messengers, kinases, transcription factors, and other miscellaneous adaptors or regulators. In this minireview, we summarize and highlight the importance of several stress signaling pathways that influence the pathogenicity of Cryptococcus and discuss future challenges in these areas. PMID:24078305

Interplay between sugar and hormone signaling pathways modulate floral signal transduction

PubMed Central

Matsoukas, Ianis G.

2014-01-01

NOMENCLATURE The following nomenclature will be used in this article: Names of genes are written in italicized upper-case letters, e.g., ABI4.Names of proteins are written in non-italicized upper-case letters, e.g., ABI4.Names of mutants are written in italicized lower-case letters, e.g., abi4. The juvenile-to-adult and vegetative-to-reproductive phase transitions are major determinants of plant reproductive success and adaptation to the local environment. Understanding the intricate molecular genetic and physiological machinery by which environment regulates juvenility and floral signal transduction has significant scientific and economic implications. Sugars are recognized as important regulatory molecules that regulate cellular activity at multiple levels, from transcription and translation to protein stability and activity. Molecular genetic and physiological approaches have demonstrated different aspects of carbohydrate involvement and its interactions with other signal transduction pathways in regulation of the juvenile-to-adult and vegetative-to-reproductive phase transitions. Sugars regulate juvenility and floral signal transduction through their function as energy sources, osmotic regulators and signaling molecules. Interestingly, sugar signaling has been shown to involve extensive connections with phytohormone signaling. This includes interactions with phytohormones that are also important for the orchestration of developmental phase transitions, including gibberellins, abscisic acid, ethylene, and brassinosteroids. This article highlights the potential roles of sugar-hormone interactions in regulation of floral signal transduction, with particular emphasis on Arabidopsis thaliana mutant phenotypes, and suggests possible directions for future research. PMID:25165468

Interplay between sugar and hormone signaling pathways modulate floral signal transduction.

PubMed

Matsoukas, Ianis G

2014-01-01

NOMENCLATURE The following nomenclature will be used in this article: Names of genes are written in italicized upper-case letters, e.g., ABI4.Names of proteins are written in non-italicized upper-case letters, e.g., ABI4.Names of mutants are written in italicized lower-case letters, e.g., abi4. The juvenile-to-adult and vegetative-to-reproductive phase transitions are major determinants of plant reproductive success and adaptation to the local environment. Understanding the intricate molecular genetic and physiological machinery by which environment regulates juvenility and floral signal transduction has significant scientific and economic implications. Sugars are recognized as important regulatory molecules that regulate cellular activity at multiple levels, from transcription and translation to protein stability and activity. Molecular genetic and physiological approaches have demonstrated different aspects of carbohydrate involvement and its interactions with other signal transduction pathways in regulation of the juvenile-to-adult and vegetative-to-reproductive phase transitions. Sugars regulate juvenility and floral signal transduction through their function as energy sources, osmotic regulators and signaling molecules. Interestingly, sugar signaling has been shown to involve extensive connections with phytohormone signaling. This includes interactions with phytohormones that are also important for the orchestration of developmental phase transitions, including gibberellins, abscisic acid, ethylene, and brassinosteroids. This article highlights the potential roles of sugar-hormone interactions in regulation of floral signal transduction, with particular emphasis on Arabidopsis thaliana mutant phenotypes, and suggests possible directions for future research.

A chloroplast retrograde signal, 3’-phosphoadenosine 5’-phosphate, acts as a secondary messenger in abscisic acid signaling in stomatal closure and germination

PubMed Central

Pornsiriwong, Wannarat; Estavillo, Gonzalo M; Chan, Kai Xun; Tee, Estee E; Ganguly, Diep; Crisp, Peter A; Phua, Su Yin; Zhao, Chenchen; Qiu, Jiaen; Park, Jiyoung; Yong, Miing Tiem; Nisar, Nazia; Yadav, Arun Kumar; Schwessinger, Benjamin; Rathjen, John; Cazzonelli, Christopher I; Wilson, Philippa B; Gilliham, Matthew; Chen, Zhong-Hua; Pogson, Barry J

2017-01-01

Organelle-nuclear retrograde signaling regulates gene expression, but its roles in specialized cells and integration with hormonal signaling remain enigmatic. Here we show that the SAL1-PAP (3′-phosphoadenosine 5′- phosphate) retrograde pathway interacts with abscisic acid (ABA) signaling to regulate stomatal closure and seed germination in Arabidopsis. Genetically or exogenously manipulating PAP bypasses the canonical signaling components ABA Insensitive 1 (ABI1) and Open Stomata 1 (OST1); priming an alternative pathway that restores ABA-responsive gene expression, ROS bursts, ion channel function, stomatal closure and drought tolerance in ost1-2. PAP also inhibits wild type and abi1-1 seed germination by enhancing ABA sensitivity. PAP-XRN signaling interacts with ABA, ROS and Ca2+; up-regulating multiple ABA signaling components, including lowly-expressed Calcium Dependent Protein Kinases (CDPKs) capable of activating the anion channel SLAC1. Thus, PAP exhibits many secondary messenger attributes and exemplifies how retrograde signals can have broader roles in hormone signaling, allowing chloroplasts to fine-tune physiological responses. DOI: http://dx.doi.org/10.7554/eLife.23361.001 PMID:28323614

Differential Cellular Responses to Hedgehog Signalling in Vertebrates—What is the Role of Competence?

PubMed Central

Kiecker, Clemens; Graham, Anthony; Logan, Malcolm

2016-01-01

A surprisingly small number of signalling pathways generate a plethora of cellular responses ranging from the acquisition of multiple cell fates to proliferation, differentiation, morphogenesis and cell death. These diverse responses may be due to the dose-dependent activities of signalling factors, or to intrinsic differences in the response of cells to a given signal—a phenomenon called differential cellular competence. In this review, we focus on temporal and spatial differences in competence for Hedgehog (HH) signalling, a signalling pathway that is reiteratively employed in embryos and adult organisms. We discuss the upstream signals and mechanisms that may establish differential competence for HHs in a range of different tissues. We argue that the changing competence for HH signalling provides a four-dimensional framework for the interpretation of the signal that is essential for the emergence of functional anatomy. A number of diseases—including several types of cancer—are caused by malfunctions of the HH pathway. A better understanding of what provides differential competence for this signal may reveal HH-related disease mechanisms and equip us with more specific tools to manipulate HH signalling in the clinic. PMID:29615599

Recruitment-dance signals draw larger audiences when honey bee colonies have multiple patrilines

PubMed Central

Mattila, H. R.; Seeley, T. D.

2010-01-01

Honey bee queens (Apis mellifera) who mate with multiple males produce colonies that are filled with numerous genetically distinct patrilines of workers. A genetically diverse colony benefits from an enhanced foraging effort, fuelled in part by an increase in the number of recruitment signals that are produced by foragers. However, the influence of patriline diversity on the attention paid to these signals by audiences of potentially receptive workers remains unexplored. To determine whether recruitment dances performed by foragers in multiple-patriline colonies attract a greater number of dance followers than dances in colonies that lack patriline diversity, we trained workers from multiple- and single-patriline colonies to forage in a greenhouse and monitored their dance-following activity back in the hives. On average, more workers followed a dance if it was performed in a multiple-patriline colony rather than a single-patriline colony (33% increase), and for a greater number of dance circuits per follower. Furthermore, dance-following workers in multiple-patriline colonies were more likely to exit their hive after following a dance, although this did not translate to a difference in colony-level exit rates between treatment types. Recruiting nest mates to profitable food sources through dance communication is critical to a colony’s foraging success and long-term fitness; polyandrous queens produce colonies that benefit not only from increased recruitment signalling, but also from the generation of larger and more attentive audiences of signal receivers. This study highlights the importance of integrating responses of both signal senders and receivers to understand more fully the success of animal-communication systems. PMID:21350596

Recruitment-dance signals draw larger audiences when honey bee colonies have multiple patrilines.

PubMed

Girard, M B; Mattila, H R; Seeley, T D

2011-02-01

Honey bee queens (Apis mellifera) who mate with multiple males produce colonies that are filled with numerous genetically distinct patrilines of workers. A genetically diverse colony benefits from an enhanced foraging effort, fuelled in part by an increase in the number of recruitment signals that are produced by foragers. However, the influence of patriline diversity on the attention paid to these signals by audiences of potentially receptive workers remains unexplored. To determine whether recruitment dances performed by foragers in multiple-patriline colonies attract a greater number of dance followers than dances in colonies that lack patriline diversity, we trained workers from multiple- and single-patriline colonies to forage in a greenhouse and monitored their dance-following activity back in the hives. On average, more workers followed a dance if it was performed in a multiple-patriline colony rather than a single-patriline colony (33% increase), and for a greater number of dance circuits per follower. Furthermore, dance-following workers in multiple-patriline colonies were more likely to exit their hive after following a dance, although this did not translate to a difference in colony-level exit rates between treatment types. Recruiting nest mates to profitable food sources through dance communication is critical to a colony's foraging success and long-term fitness; polyandrous queens produce colonies that benefit not only from increased recruitment signalling, but also from the generation of larger and more attentive audiences of signal receivers. This study highlights the importance of integrating responses of both signal senders and receivers to understand more fully the success of animal-communication systems.

SPROC: A multiple-processor DSP IC

NASA Technical Reports Server (NTRS)

Davis, R.

1991-01-01

A large, single-chip, multiple-processor, digital signal processing (DSP) integrated circuit (IC) fabricated in HP-Cmos34 is presented. The innovative architecture is best suited for analog and real-time systems characterized by both parallel signal data flows and concurrent logic processing. The IC is supported by a powerful development system that transforms graphical signal flow graphs into production-ready systems in minutes. Automatic compiler partitioning of tasks among four on-chip processors gives the IC the signal processing power of several conventional DSP chips.

The life cycle of chondrocytes in the developing skeleton

PubMed Central

Shum, Lillian; Nuckolls, Glen

2002-01-01

Cartilage serves multiple functions in the developing embryo and in postnatal life. Genetic mutations affecting cartilage development are relatively common and lead to skeletal malformations, dysfunction or increased susceptibility to disease or injury. Characterization of these mutations and investigation of the molecular pathways in which these genes function have contributed to an understanding of the mechanisms regulating skeletal patterning, chondrogenesis, endochondral ossification and joint formation. Extracellular growth and differentiation factors including bone morphogenetic proteins, fibroblast growth factors, parathyroid hormone-related peptide, extracellular matrix components, and members of the hedgehog and Wnt families provide important signals for the regulation of cell proliferation, differentiation and apoptosis. Transduction of these signals within the developing mesenchymal cells and chondrocytes results in changes in gene expression mediated by transcription factors including Smads, Msx2, Sox9, signal transducer and activator of transcription (STAT), and core-binding factor alpha 1. Further investigation of the interactions of these signaling pathways will contribute to an understanding of cartilage growth and development, and will allow for the development of strategies for the early detection, prevention and treatment of diseases and disorders affecting the skeleton. PMID:11879545

An Adaptable Multiple Power Source for Mass Spectrometry and other Scientific Instruments

DOE PAGES

Lin, Tzu-Yung; Anderson, Gordon A.; Norheim, Randolph V.; ...

2015-09-18

Power supplies are commonly used in the operation of many types of scientific equipment, including mass spectrometers and ancillary instrumentation. A generic modern mass spectrometer comprises an ionization source, such as electrospray ionization (ESI), ion transfer devices such as ion funnels and multipole ion guides, and ion signal detection apparatus. Very often such platforms include, or are interfaced with ancillary elements in order to manipulate samples before or after ionization. In order to operate such scientific instruments, numerous direct current (DC) channels and radio frequency (RF) signals are required, along with other controls such as temperature regulation. In particular, DCmore » voltages in the range of ±400 V, along with MHz range RF signals with peak-to-peak amplitudes in the hundreds of volts range are commonly used to transfer ionized samples under vacuum. Additionally, an ESI source requires a high voltage (HV) DC source capable of producing several thousand volts and heaters capable of generating temperatures up to 300°C. All of these signals must be properly synchronized and managed in order to carry out ion trapping, accumulation and detection.« less

Measuring Ocean Surface Waves using Signal Reflections from Geostationary Satellites

NASA Astrophysics Data System (ADS)

Ouellette, J. D.; Dowgiallo, D. J.; Hwang, P. A.; Toporkov, J. V.

2017-12-01

The delay-Doppler response of communications signals (such as GNSS) reflected off the ocean surface is well-known to have properties which strongly correlate with surface wind conditions and ocean surface roughness. This study extends reflectometry techniques currently applied to the GNSS constellation to include geostationary communications satellites such as XM Radio. In this study, ocean wind conditions and significant wave height will be characterized using the delay-Doppler response of XM Radio signals reflected off of ocean surface waves. Using geostationary satellites for reflectometry-based remote sensing of oceans presents two primary advantages. First, longer coherent integration times can be achieved, which boosts signal processing gain and allows for finer Doppler resolution. Second, being designed for wide-area broadcast communications, the ground-received power of these geostationary satellite signals tends to be many orders of magnitude stronger than e.g. GNSS signals. Reflections of such signals from the ocean are strong enough to be received well outside of the specular region. This flexibility of viewing geometry allows signal processing to be performed on data received from multiple incidence/reception angles, which can provide a more complete characterization of ocean surface roughness and surface wind vectors. This work will include studies of simulated and measured delay-Doppler behavior of XM Radio signals reflected from dynamic ocean surfaces. Simulation studies will include inter-comparison between a number of hydrodynamic and electromagnetic models. Results from simulations will be presented as delay-Doppler plots and will be compared with delay-Doppler behavior observed in measured data. Measured data will include field campaign results from early- to mid-2017 in which the US Naval Research Laboratory's in-house XM reflectometer-receiver was deployed near the coasts of Virginia and North Carolina to observe reflections from wind-driven ocean waves. Preliminary results from a significant wave height retrieval algorithm will also be presented.

Multiple-output support vector machine regression with feature selection for arousal/valence space emotion assessment.

PubMed

Torres-Valencia, Cristian A; Álvarez, Mauricio A; Orozco-Gutiérrez, Alvaro A

2014-01-01

Human emotion recognition (HER) allows the assessment of an affective state of a subject. Until recently, such emotional states were described in terms of discrete emotions, like happiness or contempt. In order to cover a high range of emotions, researchers in the field have introduced different dimensional spaces for emotion description that allow the characterization of affective states in terms of several variables or dimensions that measure distinct aspects of the emotion. One of the most common of such dimensional spaces is the bidimensional Arousal/Valence space. To the best of our knowledge, all HER systems so far have modelled independently, the dimensions in these dimensional spaces. In this paper, we study the effect of modelling the output dimensions simultaneously and show experimentally the advantages in modeling them in this way. We consider a multimodal approach by including features from the Electroencephalogram and a few physiological signals. For modelling the multiple outputs, we employ a multiple output regressor based on support vector machines. We also include an stage of feature selection that is developed within an embedded approach known as Recursive Feature Elimination (RFE), proposed initially for SVM. The results show that several features can be eliminated using the multiple output support vector regressor with RFE without affecting the performance of the regressor. From the analysis of the features selected in smaller subsets via RFE, it can be observed that the signals that are more informative into the arousal and valence space discrimination are the EEG, Electrooculogram/Electromiogram (EOG/EMG) and the Galvanic Skin Response (GSR).

Central insulin action in energy and glucose homeostasis.

PubMed

Plum, Leona; Belgardt, Bengt F; Brüning, Jens C

2006-07-01

Insulin has pleiotropic biological effects in virtually all tissues. However, the relevance of insulin signaling in peripheral tissues has been studied far more extensively than its role in the brain. An evolving body of evidence indicates that in the brain, insulin is involved in multiple regulatory mechanisms including neuronal survival, learning, and memory, as well as in regulation of energy homeostasis and reproductive endocrinology. Here we review insulin's role as a central homeostatic signal with regard to energy and glucose homeostasis and discuss the mechanisms by which insulin communicates information about the body's energy status to the brain. Particular emphasis is placed on the controversial current debate about the similarities and differences between hypothalamic insulin and leptin signaling at the molecular level.

Leptin signaling and leptin resistance

PubMed Central

Zhou, Yingjiang; Rui, Liangyou

2014-01-01

Leptin is secreted into the bloodstream by adipocytes and is required for the maintenance of energy homeostasis and body weight. Leptin deficiency or genetic defects in the components of the leptin signaling pathways causes obesity. Leptin controls energy balance and body weight primarily by targeting LEPRb-expressing neurons in the brain, particularly in the hypothalamus. These LEPRb-expressing neurons function as the first-order neurons that project to the second-order neurons located within and outside the hypothalamus, forming a neural network that controls the energy homeostasis and body weight. Multiple factors, including inflammation and ER stress, contribute to leptin resistance, and leptin resistance is the key risk factor for obesity. This review is focused on recent advance about leptin action, leptin signaling, and leptin resistance. PMID:23580174

Linear and nonlinear transparencies in binocular vision.

PubMed Central

Langley, K; Fleet, D J; Hibbard, P B

1998-01-01

When the product of a vertical square-wave grating (contrast envelope) and a horizontal sinusoidal grating (carrier) are viewed binocularly with different disparity cues they can be perceived transparently at different depths. We found, however, that the transparency was asymmetric; it only occurred when the envelope was perceived to be the overlaying surface. When the same two signals were added, the percept of transparency was symmetrical; either signal could be seen in front of or behind the other at different depths. Differences between these multiplicative and additive signal combinations were examined in two experiments. In one, we measured disparity thresholds for transparency as a function of the spatial frequency of the envelope. In the other, we measured disparity discrimination thresholds. In both experiments the thresholds for the multiplicative condition, unlike the additive condition, showed distinct minima at low envelope frequencies. The different sensitivity curves found for multiplicative and additive signal combinations suggest that different processes mediated the disparity signal. The data are consistent with a two-channel model of binocular matching, with multiple depth cues represented at single retinal locations. PMID:9802240

A speed guidance strategy for multiple signalized intersections based on car-following model

NASA Astrophysics Data System (ADS)

Tang, Tie-Qiao; Yi, Zhi-Yan; Zhang, Jian; Wang, Tao; Leng, Jun-Qiang

2018-04-01

Signalized intersection has great roles in urban traffic system. The signal infrastructure and the driving behavior near the intersection are paramount factors that have significant impacts on traffic flow and energy consumption. In this paper, a speed guidance strategy is introduced into a car-following model to study the driving behavior and the fuel consumption in a single-lane road with multiple signalized intersections. The numerical results indicate that the proposed model can reduce the fuel consumption and the average stop times. The findings provide insightful guidance for the eco-driving strategies near the signalized intersections.

Multiple bio-monitoring system using visible light for electromagnetic-wave free indoor healthcare

NASA Astrophysics Data System (ADS)

An, Jinyoung; Pham, Ngoc Quan; Chung, Wan-Young

2017-12-01

In this paper, a multiple biomedical data transmission system with visible light communication (VLC) is proposed for an electromagnetic-wave-free indoor healthcare. VLC technology has emerged as an alternative solution to radio-frequency (RF) wireless systems, due to its various merits, e.g., ubiquity, power efficiency, no RF radiation, and security. With VLC, critical bio-medical signals, including electrocardiography (ECG), can be transmitted in places where RF radiation is restricted. This potential advantage of VLC could save more lives in emergency situations. A time hopping (TH) scheme is employed to transfer multiple medical-data streams in real time with a simple system design. Multiple data streams are transmitted using identical color LEDs and go into an optical detector. The received multiple data streams are demodulated and rearranged using a TH-based demodulator. The medical data is then monitored and managed to provide the necessary medical care for each patient.

Analysis of corkscrew signaling in the Drosophila epidermal growth factor receptor pathway during myogenesis.

PubMed

Johnson Hamlet, M R; Perkins, L A

2001-11-01

The Drosophila nonreceptor protein tyrosine phosphatase, Corkscrew (Csw), functions positively in multiple receptor tyrosine kinase (RTK) pathways, including signaling by the epidermal growth factor receptor (EGFR). Detailed phenotypic analyses of csw mutations have revealed that Csw activity is required in many of the same developmental processes that require EGFR function. However, it is still unclear where in the signaling hierarchy Csw functions relative to other proteins whose activities are also required downstream of the receptor. To address this issue, genetic interaction experiments were performed to place csw gene activity relative to the EGFR, spitz (spi), rhomboid (rho), daughter of sevenless (DOS), kinase-suppressor of ras (ksr), ras1, D-raf, pointed (pnt), and moleskin. We followed the EGFR-dependent formation of VA2 muscle precursor cells as a sensitive assay for these genetic interaction studies. First, we established that Csw has a positive function during mesoderm development. Second, we found that tissue-specific expression of a gain-of-function csw construct rescues loss-of-function mutations in other positive signaling genes upstream of rolled (rl)/MAPK in the EGFR pathway. Third, we were able to infer levels of EGFR signaling in various mutant backgrounds during myogenesis. This work extends previous studies of Csw during Torso and Sevenless RTK signaling to include an in-depth analysis of the role of Csw in the EGFR signaling pathway.

Analysis of corkscrew signaling in the Drosophila epidermal growth factor receptor pathway during myogenesis.

PubMed Central

Johnson Hamlet, M R; Perkins, L A

2001-01-01

The Drosophila nonreceptor protein tyrosine phosphatase, Corkscrew (Csw), functions positively in multiple receptor tyrosine kinase (RTK) pathways, including signaling by the epidermal growth factor receptor (EGFR). Detailed phenotypic analyses of csw mutations have revealed that Csw activity is required in many of the same developmental processes that require EGFR function. However, it is still unclear where in the signaling hierarchy Csw functions relative to other proteins whose activities are also required downstream of the receptor. To address this issue, genetic interaction experiments were performed to place csw gene activity relative to the EGFR, spitz (spi), rhomboid (rho), daughter of sevenless (DOS), kinase-suppressor of ras (ksr), ras1, D-raf, pointed (pnt), and moleskin. We followed the EGFR-dependent formation of VA2 muscle precursor cells as a sensitive assay for these genetic interaction studies. First, we established that Csw has a positive function during mesoderm development. Second, we found that tissue-specific expression of a gain-of-function csw construct rescues loss-of-function mutations in other positive signaling genes upstream of rolled (rl)/MAPK in the EGFR pathway. Third, we were able to infer levels of EGFR signaling in various mutant backgrounds during myogenesis. This work extends previous studies of Csw during Torso and Sevenless RTK signaling to include an in-depth analysis of the role of Csw in the EGFR signaling pathway. PMID:11729154

Detection of Multiple Innervation Zones from Multi-Channel Surface EMG Recordings with Low Signal-to-Noise Ratio Using Graph-Cut Segmentation.

PubMed

Marateb, Hamid Reza; Farahi, Morteza; Rojas, Monica; Mañanas, Miguel Angel; Farina, Dario

2016-01-01

Knowledge of the location of muscle Innervation Zones (IZs) is important in many applications, e.g. for minimizing the quantity of injected botulinum toxin for the treatment of spasticity or for deciding on the type of episiotomy during child delivery. Surface EMG (sEMG) can be noninvasively recorded to assess physiological and morphological characteristics of contracting muscles. However, it is not often possible to record signals of high quality. Moreover, muscles could have multiple IZs, which should all be identified. We designed a fully-automatic algorithm based on the enhanced image Graph-Cut segmentation and morphological image processing methods to identify up to five IZs in 60-ms intervals of very-low to moderate quality sEMG signal detected with multi-channel electrodes (20 bipolar channels with Inter Electrode Distance (IED) of 5 mm). An anisotropic multilayered cylinder model was used to simulate 750 sEMG signals with signal-to-noise ratio ranging from -5 to 15 dB (using Gaussian noise) and in each 60-ms signal frame, 1 to 5 IZs were included. The micro- and macro- averaged performance indices were then reported for the proposed IZ detection algorithm. In the micro-averaging procedure, the number of True Positives, False Positives and False Negatives in each frame were summed up to generate cumulative measures. In the macro-averaging, on the other hand, precision and recall were calculated for each frame and their averages are used to determine F1-score. Overall, the micro (macro)-averaged sensitivity, precision and F1-score of the algorithm for IZ channel identification were 82.7% (87.5%), 92.9% (94.0%) and 87.5% (90.6%), respectively. For the correctly identified IZ locations, the average bias error was of 0.02±0.10 IED ratio. Also, the average absolute conduction velocity estimation error was 0.41±0.40 m/s for such frames. The sensitivity analysis including increasing IED and reducing interpolation coefficient for time samples was performed. Meanwhile, the effect of adding power-line interference and using other image interpolation methods on the deterioration of the performance of the proposed algorithm was investigated. The average running time of the proposed algorithm on each 60-ms sEMG frame was 25.5±8.9 (s) on an Intel dual-core 1.83 GHz CPU with 2 GB of RAM. The proposed algorithm correctly and precisely identified multiple IZs in each signal epoch in a wide range of signal quality and is thus a promising new offline tool for electrophysiological studies.

Detection of Multiple Innervation Zones from Multi-Channel Surface EMG Recordings with Low Signal-to-Noise Ratio Using Graph-Cut Segmentation

PubMed Central

Farahi, Morteza; Rojas, Monica; Mañanas, Miguel Angel; Farina, Dario

2016-01-01

Knowledge of the location of muscle Innervation Zones (IZs) is important in many applications, e.g. for minimizing the quantity of injected botulinum toxin for the treatment of spasticity or for deciding on the type of episiotomy during child delivery. Surface EMG (sEMG) can be noninvasively recorded to assess physiological and morphological characteristics of contracting muscles. However, it is not often possible to record signals of high quality. Moreover, muscles could have multiple IZs, which should all be identified. We designed a fully-automatic algorithm based on the enhanced image Graph-Cut segmentation and morphological image processing methods to identify up to five IZs in 60-ms intervals of very-low to moderate quality sEMG signal detected with multi-channel electrodes (20 bipolar channels with Inter Electrode Distance (IED) of 5 mm). An anisotropic multilayered cylinder model was used to simulate 750 sEMG signals with signal-to-noise ratio ranging from -5 to 15 dB (using Gaussian noise) and in each 60-ms signal frame, 1 to 5 IZs were included. The micro- and macro- averaged performance indices were then reported for the proposed IZ detection algorithm. In the micro-averaging procedure, the number of True Positives, False Positives and False Negatives in each frame were summed up to generate cumulative measures. In the macro-averaging, on the other hand, precision and recall were calculated for each frame and their averages are used to determine F1-score. Overall, the micro (macro)-averaged sensitivity, precision and F1-score of the algorithm for IZ channel identification were 82.7% (87.5%), 92.9% (94.0%) and 87.5% (90.6%), respectively. For the correctly identified IZ locations, the average bias error was of 0.02±0.10 IED ratio. Also, the average absolute conduction velocity estimation error was 0.41±0.40 m/s for such frames. The sensitivity analysis including increasing IED and reducing interpolation coefficient for time samples was performed. Meanwhile, the effect of adding power-line interference and using other image interpolation methods on the deterioration of the performance of the proposed algorithm was investigated. The average running time of the proposed algorithm on each 60-ms sEMG frame was 25.5±8.9 (s) on an Intel dual-core 1.83 GHz CPU with 2 GB of RAM. The proposed algorithm correctly and precisely identified multiple IZs in each signal epoch in a wide range of signal quality and is thus a promising new offline tool for electrophysiological studies. PMID:27978535

Blind Equalization and Fading Channel Signal Recovery of OFDM Modulation

DTIC Science & Technology

2011-03-01

Square LTI Linear Time Invariant MIMO Multiple-Input Multiple-Output OFDM Orthogonal Frequency-Division Multiplexing QPSK Quadrature Phase-Shift...AND FADING CHANNEL SIGNAL RECOVERY OF OFDM MODULATION by Anthony G. Stranges March 2011 Thesis Co-Advisors: Roberto Cristi Frank Kragh...Master’s Thesis 4. TITLE AND SUBTITLE Blind Equalization and Fading Channel Signal Recovery of OFDM Modulation 6. AUTHOR(S) Anthony G. Stranges

SENP1 inhibition induces apoptosis and growth arrest of multiple myeloma cells through modulation of NF-κB signaling

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

Xu, Jun; Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850; Sun, Hui-Yan

2015-05-01

SUMO/sentrin specific protease 1 (Senp1) is an important regulation protease in the protein sumoylation, which affects the cell cycle, proliferation and differentiation. The role of Senp1 mediated protein desumoylation in pathophysiological progression of multiple myeloma is unknown. In this study, we demonstrated that Senp1 is overexpressed and induced by IL-6 in multiple myeloma cells. Lentivirus-mediated Senp1 knockdown triggers apoptosis and reduces viability, proliferation and colony forming ability of MM cells. The NF-κB family members including P65 and inhibitor protein IkBα play important roles in regulation of MM cell survival and proliferation. We further demonstrated that Senp1 inhibition decreased IL-6-induced P65more » and IkBα phosphorylation, leading to inactivation of NF-kB signaling in MM cells. These results delineate a key role for Senp1in IL-6 induced proliferation and survival of MM cells, suggesting it may be a potential new therapeutic target in MM. - Highlights: • Senp1 is overexpressed and induced by IL-6 in multiple myeloma cells. • Senp1 knockdown triggers apoptosis and reduces proliferation of MM cells. • Senp1 inhibition decreased IL-6-induced P65 and IkBα phosphorylation.« less

Demonstration of an SOA-assisted open metro-access infrastructure for heterogeneous services.

PubMed

Schmuck, H; Bonk, R; Poehlmann, W; Haslach, C; Kuebart, W; Karnick, D; Meyer, J; Fritzsche, D; Weis, E; Becker, J; Freude, W; Pfeiffer, T

2014-01-13

An open converged metro-access network approach allows for sharing optical layer resources like fibers and optical spectrum among different services and operators. We demonstrated experimentally the feasibility of such a concept by the simultaneous operation of multiple services showing different modulation formats and multiplexing techniques. Flexible access nodes are implemented including semiconductor optical amplifiers to create a transparent and reconfigurable optical ring network. The impact of cascaded optical amplifiers on the signal quality is studied along the ring. In addition, the influence of high power rival signals in the same waveband and in the same fiber is analyzed.

Bacterial Serine/Threonine Protein Kinases in Host-Pathogen Interactions*

PubMed Central

Canova, Marc J.; Molle, Virginie

2014-01-01

In bacterial pathogenesis, monitoring and adapting to the dynamically changing environment in the host and an ability to disrupt host immune responses are critical. The virulence determinants of pathogenic bacteria include the sensor/signaling proteins of the serine/threonine protein kinase (STPK) family that have a dual role of sensing the environment and subverting specific host defense processes. STPKs can sense a wide range of signals and coordinate multiple cellular processes to mount an appropriate response. Here, we review some of the well studied bacterial STPKs that are essential virulence factors and that modify global host responses during infection. PMID:24554701

Bacterial serine/threonine protein kinases in host-pathogen interactions.

PubMed

Canova, Marc J; Molle, Virginie

2014-04-04

In bacterial pathogenesis, monitoring and adapting to the dynamically changing environment in the host and an ability to disrupt host immune responses are critical. The virulence determinants of pathogenic bacteria include the sensor/signaling proteins of the serine/threonine protein kinase (STPK) family that have a dual role of sensing the environment and subverting specific host defense processes. STPKs can sense a wide range of signals and coordinate multiple cellular processes to mount an appropriate response. Here, we review some of the well studied bacterial STPKs that are essential virulence factors and that modify global host responses during infection.

The extraction of simple relationships in growth factor-specific multiple-input and multiple-output systems in cell-fate decisions by backward elimination PLS regression.

PubMed

Akimoto, Yuki; Yugi, Katsuyuki; Uda, Shinsuke; Kudo, Takamasa; Komori, Yasunori; Kubota, Hiroyuki; Kuroda, Shinya

2013-01-01

Cells use common signaling molecules for the selective control of downstream gene expression and cell-fate decisions. The relationship between signaling molecules and downstream gene expression and cellular phenotypes is a multiple-input and multiple-output (MIMO) system and is difficult to understand due to its complexity. For example, it has been reported that, in PC12 cells, different types of growth factors activate MAP kinases (MAPKs) including ERK, JNK, and p38, and CREB, for selective protein expression of immediate early genes (IEGs) such as c-FOS, c-JUN, EGR1, JUNB, and FOSB, leading to cell differentiation, proliferation and cell death; however, how multiple-inputs such as MAPKs and CREB regulate multiple-outputs such as expression of the IEGs and cellular phenotypes remains unclear. To address this issue, we employed a statistical method called partial least squares (PLS) regression, which involves a reduction of the dimensionality of the inputs and outputs into latent variables and a linear regression between these latent variables. We measured 1,200 data points for MAPKs and CREB as the inputs and 1,900 data points for IEGs and cellular phenotypes as the outputs, and we constructed the PLS model from these data. The PLS model highlighted the complexity of the MIMO system and growth factor-specific input-output relationships of cell-fate decisions in PC12 cells. Furthermore, to reduce the complexity, we applied a backward elimination method to the PLS regression, in which 60 input variables were reduced to 5 variables, including the phosphorylation of ERK at 10 min, CREB at 5 min and 60 min, AKT at 5 min and JNK at 30 min. The simple PLS model with only 5 input variables demonstrated a predictive ability comparable to that of the full PLS model. The 5 input variables effectively extracted the growth factor-specific simple relationships within the MIMO system in cell-fate decisions in PC12 cells.

Towards Efficient Decoding of Multiple Classes of Motor Imagery Limb Movements Based on EEG Spectral and Time Domain Descriptors.

PubMed

Samuel, Oluwarotimi Williams; Geng, Yanjuan; Li, Xiangxin; Li, Guanglin

2017-10-28

To control multiple degrees of freedom (MDoF) upper limb prostheses, pattern recognition (PR) of electromyogram (EMG) signals has been successfully applied. This technique requires amputees to provide sufficient EMG signals to decode their limb movement intentions (LMIs). However, amputees with neuromuscular disorder/high level amputation often cannot provide sufficient EMG control signals, and thus the applicability of the EMG-PR technique is limited especially to this category of amputees. As an alternative approach, electroencephalograph (EEG) signals recorded non-invasively from the brain have been utilized to decode the LMIs of humans. However, most of the existing EEG based limb movement decoding methods primarily focus on identifying limited classes of upper limb movements. In addition, investigation on EEG feature extraction methods for the decoding of multiple classes of LMIs has rarely been considered. Therefore, 32 EEG feature extraction methods (including 12 spectral domain descriptors (SDDs) and 20 time domain descriptors (TDDs)) were used to decode multiple classes of motor imagery patterns associated with different upper limb movements based on 64-channel EEG recordings. From the obtained experimental results, the best individual TDD achieved an accuracy of 67.05 ± 3.12% as against 87.03 ± 2.26% for the best SDD. By applying a linear feature combination technique, an optimal set of combined TDDs recorded an average accuracy of 90.68% while that of the SDDs achieved an accuracy of 99.55% which were significantly higher than those of the individual TDD and SDD at p < 0.05. Our findings suggest that optimal feature set combination would yield a relatively high decoding accuracy that may improve the clinical robustness of MDoF neuroprosthesis. The study was approved by the ethics committee of Institutional Review Board of Shenzhen Institutes of Advanced Technology, and the reference number is SIAT-IRB-150515-H0077.

Photonic-assisted microwave signal multiplication and modulation using a silicon Mach–Zehnder modulator

PubMed Central

Long, Yun; Zhou, Linjie; Wang, Jian

2016-01-01

Photonic generation of microwave signal is obviously attractive for many prominent advantages, such as large bandwidth, low loss, and immunity to electromagnetic interference. Based on a single integrated silicon Mach–Zehnder modulator (MZM), we propose and experimentally demonstrate a simple and compact photonic scheme to enable frequency-multiplicated microwave signal. Using the fabricated integrated MZM, we also demonstrate the feasibility of microwave amplitude-shift keying (ASK) modulation based on integrated photonic approach. In proof-of-concept experiments, 2-GHz frequency-doubled microwave signal is generated using a 1-GHz driving signal. 750-MHz/1-GHz frequency-tripled/quadrupled microwave signals are obtained with a driving signal of 250 MHz. In addition, a 50-Mb/s binary amplitude coded 1-GHz microwave signal is also successfully generated. PMID:26832305

Incorporating reversible and irreversible transverse relaxation effects into Steady State Free Precession (SSFP) signal intensity expressions for fMRI considerations.

PubMed

Mulkern, Robert V; Balasubramanian, Mukund; Orbach, Darren B; Mitsouras, Dimitrios; Haker, Steven J

2013-04-01

Among the multiple sequences available for functional magnetic resonance imaging (fMRI), the Steady State Free Precession (SSFP) sequence offers the highest signal-to-noise ratio (SNR) per unit time as well as distortion free images not feasible with the more commonly employed single-shot echo planar imaging (EPI) approaches. Signal changes occurring with activation in SSFP sequences reflect underlying changes in both irreversible and reversible transverse relaxation processes. The latter are characterized by changes in the central frequencies and widths of the inherent frequency distribution present within a voxel. In this work, the well-known frequency response of the SSFP signal intensity is generalized to include the widths and central frequencies of some common frequency distributions on SSFP signal intensities. The approach, using a previously unnoted series expansion, allows for a separation of reversible from irreversible transverse relaxation effects on SSFP signal intensity changes. The formalism described here should prove useful for identifying and modeling mechanisms associated with SSFP signal changes accompanying neural activation. Copyright © 2013 Elsevier Inc. All rights reserved.

Ultrasensitive response motifs: basic amplifiers in molecular signalling networks

PubMed Central

Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E.

2013-01-01

Multi-component signal transduction pathways and gene regulatory circuits underpin integrated cellular responses to perturbations. A recurring set of network motifs serve as the basic building blocks of these molecular signalling networks. This review focuses on ultrasensitive response motifs (URMs) that amplify small percentage changes in the input signal into larger percentage changes in the output response. URMs generally possess a sigmoid input–output relationship that is steeper than the Michaelis–Menten type of response and is often approximated by the Hill function. Six types of URMs can be commonly found in intracellular molecular networks and each has a distinct kinetic mechanism for signal amplification. These URMs are: (i) positive cooperative binding, (ii) homo-multimerization, (iii) multistep signalling, (iv) molecular titration, (v) zero-order covalent modification cycle and (vi) positive feedback. Multiple URMs can be combined to generate highly switch-like responses. Serving as basic signal amplifiers, these URMs are essential for molecular circuits to produce complex nonlinear dynamics, including multistability, robust adaptation and oscillation. These dynamic properties are in turn responsible for higher-level cellular behaviours, such as cell fate determination, homeostasis and biological rhythm. PMID:23615029

Coordinated photomorphogenic UV-B signaling network captured by mathematical modeling.

PubMed

Ouyang, Xinhao; Huang, Xi; Jin, Xiao; Chen, Zheng; Yang, Panyu; Ge, Hao; Li, Shigui; Deng, Xing Wang

2014-08-05

Long-wavelength and low-fluence UV-B light is an informational signal known to induce photomorphogenic development in plants. Using the model plant Arabidopsis thaliana, a variety of factors involved in UV-B-specific signaling have been experimentally characterized over the past decade, including the UV-B light receptor UV resistance locus 8; the positive regulators constitutive photomorphogenesis 1 and elongated hypocotyl 5; and the negative regulators cullin4, repressor of UV-B photomorphogenesis 1 (RUP1), and RUP2. Individual genetic and molecular studies have revealed that these proteins function in either positive or negative regulatory capacities for the sufficient and balanced transduction of photomorphogenic UV-B signal. Less is known, however, regarding how these signaling events are systematically linked. In our study, we use a systems biology approach to investigate the dynamic behaviors and correlations of multiple signaling components involved in Arabidopsis UV-B-induced photomorphogenesis. We define a mathematical representation of photomorphogenic UV-B signaling at a temporal scale. Supplemented with experimental validation, our computational modeling demonstrates the functional interaction that occurs among different protein complexes in early and prolonged response to photomorphogenic UV-B.

Neurotrophin receptor structure and interactions.

PubMed

Yano, H; Chao, M V

2000-03-01

Although ligand-induced dimerization or oligomerization of receptors is a well established mechanism of growth factor signaling, increasing evidence indicates that biological responses are often mediated by receptor trans-signaling mechanisms involving two or more receptor systems. These include G protein-coupled receptors, cytokine, growth factor and trophic factor receptors. Greater flexibility is provided when different signaling pathways are merged through multiple receptor signaling systems. Trophic factors exemplified by NGF and its family members, ciliary neurotrophic factor (CNTF) and glial derived neurotrophic factor (GDNF) all utilize increased tyrosine phosphorylation of cellular substrates to mediate neuronal cell survival. Actions of the NGF family of neurotrophins are not only dictated by ras activation through the Trk family of receptor tyrosine kinases, but also a survival pathway defined by phosphatidylinositol-3-kinase activity (Yao and Cooper, 1995), which gives rise to phosphoinositide intermediates that activate the serine/threonine kinase Akt/PKB (Dudek et al., 1997). Induction of the serine-threonine kinase activity is critical for cell survival, as well as cell proliferation. Hence, for many trophic factors, multiple proteins constitute a functional multisubunit receptor complex that activates ras-dependent and ras-independent intracellular signaling. The NGF receptors provide an example of bidirectional crosstalk. In the presence of TrkA receptors, p75 can participate in the formation of high affinity binding sites and enhanced neurotrophin responsiveness leading to a survival or differentiation signal. In the absence of TrkA receptors, p75 can generate, in only specific cell populations, a death signal. These activities include the induction of NF kappa B (Carter et al., 1996); the hydrolysis of sphingomyelin to ceramide (Dobrowsky et al., 1995); and the pro-apoptotic functions attributed to p75. Receptors are generally drawn and viewed as isolated integral membrane proteins which span the lipid bilayer, with signal transduction proceeding in a linear step-wise fashion. There are now numerous examples which indicate that each receptor acts not only in a linear, independent manner, but can also influence the activity of other cell surface receptors, either directly or through signaling intermediates. Which step and which intermediates are utilized for crosstalk between the receptors is a critical question. For neurotrophins, their primary function in sustaining the viability of neurons is counterbalanced by a receptor mechanism to eliminate cells by an apoptotic mechanism. It is conceivable that this bidirectional system may be utilized selectively during development and in neurodegenerative diseases.

Small Arrays for Seismic Intruder Detections: A Simulation Based Experiment

NASA Astrophysics Data System (ADS)

Pitarka, A.

2014-12-01

Seismic sensors such as geophones and fiber optic have been increasingly recognized as promising technologies for intelligence surveillance, including intruder detection and perimeter defense systems. Geophone arrays have the capability to provide cost effective intruder detection in protecting assets with large perimeters. A seismic intruder detection system uses one or multiple arrays of geophones design to record seismic signals from footsteps and ground vehicles. Using a series of real-time signal processing algorithms the system detects, classify and monitors the intruder's movement. We have carried out numerical experiments to demonstrate the capability of a seismic array to detect moving targets that generate seismic signals. The seismic source is modeled as a vertical force acting on the ground that generates continuous impulsive seismic signals with different predominant frequencies. Frequency-wave number analysis of the synthetic array data was used to demonstrate the array's capability at accurately determining intruder's movement direction. The performance of the array was also analyzed in detecting two or more objects moving at the same time. One of the drawbacks of using a single array system is its inefficiency at detecting seismic signals deflected by large underground objects. We will show simulation results of the effect of an underground concrete block at shielding the seismic signal coming from an intruder. Based on simulations we found that multiple small arrays can greatly improve the system's detection capability in the presence of underground structures. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344

Comparative genetic screens in human cells reveal new regulatory mechanisms in WNT signaling

PubMed Central

Lebensohn, Andres M; Dubey, Ramin; Neitzel, Leif R; Tacchelly-Benites, Ofelia; Yang, Eungi; Marceau, Caleb D; Davis, Eric M; Patel, Bhaven B; Bahrami-Nejad, Zahra; Travaglini, Kyle J; Ahmed, Yashi; Lee, Ethan; Carette, Jan E; Rohatgi, Rajat

2016-01-01

The comprehensive understanding of cellular signaling pathways remains a challenge due to multiple layers of regulation that may become evident only when the pathway is probed at different levels or critical nodes are eliminated. To discover regulatory mechanisms in canonical WNT signaling, we conducted a systematic forward genetic analysis through reporter-based screens in haploid human cells. Comparison of screens for negative, attenuating and positive regulators of WNT signaling, mediators of R-spondin-dependent signaling and suppressors of constitutive signaling induced by loss of the tumor suppressor adenomatous polyposis coli or casein kinase 1α uncovered new regulatory features at most levels of the pathway. These include a requirement for the transcription factor AP-4, a role for the DAX domain of AXIN2 in controlling β-catenin transcriptional activity, a contribution of glycophosphatidylinositol anchor biosynthesis and glypicans to R-spondin-potentiated WNT signaling, and two different mechanisms that regulate signaling when distinct components of the β-catenin destruction complex are lost. The conceptual and methodological framework we describe should enable the comprehensive understanding of other signaling systems. DOI: http://dx.doi.org/10.7554/eLife.21459.001 PMID:27996937

Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells.

PubMed

Ali, Dalia; Abuelreich, Sarah; Alkeraishan, Nora; Shwish, Najla Bin; Hamam, Rimi; Kassem, Moustapha; Alfayez, Musaad; Aldahmash, Abdullah; Alajez, Nehad M

2018-02-28

Bone marrow adipocyte formation plays a role in bone homeostasis and whole body energy metabolism. However, the transcriptional landscape and signaling pathways associated with adipocyte lineage commitment and maturation are not fully delineated. Thus, we performed global gene expression profiling during adipocyte differentiation of human bone marrow stromal (mesenchymal) stem cells (hMSCs) and identified 2,589 up-regulated and 2,583 down-regulated mRNA transcripts. Pathway analysis on the up-regulated gene list untraveled enrichment in multiple signaling pathways including insulin receptor signaling, focal Adhesion, metapathway biotransformation, a number of metabolic pathways e.g. selenium metabolism, Benzo(a)pyrene metabolism, fatty acid, triacylglycerol, ketone body metabolism, tryptophan metabolism, and catalytic cycle of mammalian flavin-containing monooxygenase (FMOs). On the other hand, pathway analysis on the down-regulated genes revealed significant enrichment in pathways related to cell cycle regulation. Based on these data, we assessed the effect of pharmacological inhibition of FAK signaling using PF-573228, PF-562271, and InsR/IGF-1R using NVP-AEW541 and GSK-1904529A on adipocyte differentiation. hMSCs exposed to FAK or IGF-1R/InsR inhibitors exhibited fewer adipocyte formation (27-58% inhibition, P <0005). Concordantly, the expression of adipocyte-specific genes AP2, AdipoQ, and CEBPα was significantly reduced. On the other hand, we did not detect significant effects on cell viability as a result of FAK or IGF-1R/InsR inhibition. Our data identified FAK and insulin signaling as important intracellular signaling pathways relevant to bone marrow adipogenesis. © 2018 The Author(s).

Method for siting detectors within a facility

DOEpatents

Gleason, Nathaniel Jeremy Meyer

2007-12-11

A method, system and article of manufacture of siting one or more detectors in a facility represented with zones are provided. Signals S.sub.i,j representing an effect in zone j in response to a release of contaminant in zone i for one or more flow conditions are provided. A candidate architecture has one or more candidate zones. A limiting case signal is determined for each flow condition for multiple candidate architectures. The limiting case signal is a smallest system signal of multiple system signals associated with a release in a zone. Each system signal is a maximum one of the signals representing the effect in the candidate zones from the release in one zone for the flow condition. For each candidate architecture, a robust limiting case signal is determined based on a minimum of the limiting case signals. One candidate architecture is selected based on the robust limiting case signals.

Phosphoproteomics analyses show subnetwork systems in T-cell receptor signaling.

PubMed

Hatano, Atsushi; Matsumoto, Masaki; Nakayama, Keiichi I

2016-10-01

A key issue in the study of signal transduction is how multiple signaling pathways are systematically integrated into the cell. We have now performed multiple phosphoproteomics analyses focused on the dynamics of the T-cell receptor (TCR) signaling network and its subsystem mediated by the Ca 2+ signaling pathway. Integration of these phosphoproteomics data sets and extraction of components of the TCR signaling network dependent on Ca 2+ signaling showed unexpected phosphorylation kinetics for candidate substrates of the Ca 2+ -dependent phosphatase calcineurin (CN) during TCR stimulation. Detailed characterization of the TCR-induced phosphorylation of a novel CN substrate, Itpkb, showed that phosphorylation of this protein is regulated by both CN and the mitogen-activated protein kinase Erk in a competitive manner. Phosphorylation of additional CN substrates was also found to be regulated by Erk and CN in a similar manner. The combination of multiple phosphoproteomics approaches thus showed two major subsystems mediated by Erk and CN in the TCR signaling network, with these subsystems regulating the phosphorylation of a group of proteins in a competitive manner. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

A Novel DFT-Based DOA Estimation by a Virtual Array Extension Using Simple Multiplications for FMCW Radar

PubMed Central

Kim, Bongseok; Kim, Sangdong; Lee, Jonghun

2018-01-01

We propose a novel discrete Fourier transform (DFT)-based direction of arrival (DOA) estimation by a virtual array extension using simple multiplications for frequency modulated continuous wave (FMCW) radar. DFT-based DOA estimation is usually employed in radar systems because it provides the advantage of low complexity for real-time signal processing. In order to enhance the resolution of DOA estimation or to decrease the missing detection probability, it is essential to have a considerable number of channel signals. However, due to constraints of space and cost, it is not easy to increase the number of channel signals. In order to address this issue, we increase the number of effective channel signals by generating virtual channel signals using simple multiplications of the given channel signals. The increase in channel signals allows the proposed scheme to detect DOA more accurately than the conventional scheme while using the same number of channel signals. Simulation results show that the proposed scheme achieves improved DOA estimation compared to the conventional DFT-based method. Furthermore, the effectiveness of the proposed scheme in a practical environment is verified through the experiment. PMID:29758016

A Novel Multiple-Access Correlation-Delay-Shift-Keying

NASA Astrophysics Data System (ADS)

Duan, J. Y.; Jiang, G. P.; Yang, H.

In Correlation-Delay-Shift-Keying (CDSK), the reference signal and the information-bearing signal are added together during a certain time delay. Because the reference signal is not strictly orthogonal to the information-bearing signal, the cross-correlation between the adjacent chaotic signal (Intra-signal Interference, ISI) will be introduced into the demodulation at the receiver. Therefore, the Bit-Error Ratio (BER) of CDSK is higher than that of Differential-Chaos-Shift-Keying (DCSK). To avoid the ISI component and enhance the BER performance of CDSK in multiuser scenario, Multiple-Access CDSK with No Intra-signal Interference (MA-CDSK-NII) is proposed. By constructing the repeated chaotic generator and applying the Walsh code sequence to modulate the reference signal, in MA-CDSK-NII, the ISI component will be eliminated during the demodulation. Gaussian approximation method is adopted here to obtain the exact performance analysis of MA-CDSK-NII over additive white Gaussian noise (AWGN) channel and Rayleigh multipath fading channels. Results show that, due to no ISI component and lower transmitting power, the BER performance of MA-CDSK-NII can be better than that of multiple-access CDSK and Code-Shifted Differential-Chaos-Shift-Keying (CS-DCSK).

Field Crickets Compensate for Unattractive Static Long-Distance Call Components by Increasing Dynamic Signalling Effort.

PubMed

McAuley, Emily M; Bertram, Susan M

2016-01-01

The evolution of multiple sexual signals presents a dilemma since individuals selecting a mate should pay attention to the most honest signal and ignore the rest; however, multiple signals may evolve if, together, they provide more information to the receiver than either one would alone. Static and dynamic signals, for instance, can act as multiple messages, providing information on different aspects of signaller quality that reflect condition at different time scales. While the nature of static signals makes them difficult or impossible for individuals to augment, dynamic signals are much more susceptible to temporary fluctuations in effort. We investigated whether male Texas field crickets, Gryllus texensis, that produce unattractive static signals compensate by dynamically increasing their calling effort. Our findings lend partial support to the compensation hypothesis, as males that called at unattractive carrier frequencies (a static trait) spent more time calling each night (a dynamic trait). Interestingly, this finding was most pronounced in males that called with attractive pulse characteristics (static traits) but did not occur in males that called with unattractive pulse characteristics. Males that signalled with unattractive pulse characteristics (duration and pause) spent less time calling through the night. Our correlative findings on wild caught males suggest that only males that signal with attractive pulse characteristics may be able to afford to pay the costs of both trait exaggeration and increased calling effort to compensate for poor carrier frequencies.

A modular cell-based biosensor using engineered genetic logic circuits to detect and integrate multiple environmental signals

PubMed Central

Wang, Baojun; Barahona, Mauricio; Buck, Martin

2013-01-01

Cells perceive a wide variety of cellular and environmental signals, which are often processed combinatorially to generate particular phenotypic responses. Here, we employ both single and mixed cell type populations, pre-programmed with engineered modular cell signalling and sensing circuits, as processing units to detect and integrate multiple environmental signals. Based on an engineered modular genetic AND logic gate, we report the construction of a set of scalable synthetic microbe-based biosensors comprising exchangeable sensory, signal processing and actuation modules. These cellular biosensors were engineered using distinct signalling sensory modules to precisely identify various chemical signals, and combinations thereof, with a quantitative fluorescent output. The genetic logic gate used can function as a biological filter and an amplifier to enhance the sensing selectivity and sensitivity of cell-based biosensors. In particular, an Escherichia coli consortium-based biosensor has been constructed that can detect and integrate three environmental signals (arsenic, mercury and copper ion levels) via either its native two-component signal transduction pathways or synthetic signalling sensors derived from other bacteria in combination with a cell-cell communication module. We demonstrate how a modular cell-based biosensor can be engineered predictably using exchangeable synthetic gene circuit modules to sense and integrate multiple-input signals. This study illustrates some of the key practical design principles required for the future application of these biosensors in broad environmental and healthcare areas. PMID:22981411

Digital processing of array seismic recordings

USGS Publications Warehouse

Ryall, Alan; Birtill, John

1962-01-01

This technical letter contains a brief review of the operations which are involved in digital processing of array seismic recordings by the methods of velocity filtering, summation, cross-multiplication and integration, and by combinations of these operations (the "UK Method" and multiple correlation). Examples are presented of analyses by the several techniques on array recordings which were obtained by the U.S. Geological Survey during chemical and nuclear explosions in the western United States. Seismograms are synthesized using actual noise and Pn-signal recordings, such that the signal-to-noise ratio, onset time and velocity of the signal are predetermined for the synthetic record. These records are then analyzed by summation, cross-multiplication, multiple correlation and the UK technique, and the results are compared. For all of the examples presented, analysis by the non-linear techniques of multiple correlation and cross-multiplication of the traces on an array recording are preferred to analyses by the linear operations involved in summation and the UK Method.

Optimal space communications techniques. [using digital and phase locked systems for signal processing

NASA Technical Reports Server (NTRS)

Schilling, D. L.

1974-01-01

Digital multiplication of two waveforms using delta modulation (DM) is discussed. It is shown that while conventional multiplication of two N bit words requires N2 complexity, multiplication using DM requires complexity which increases linearly with N. Bounds on the signal-to-quantization noise ratio (SNR) resulting from this multiplication are determined and compared with the SNR obtained using standard multiplication techniques. The phase locked loop (PLL) system, consisting of a phase detector, voltage controlled oscillator, and a linear loop filter, is discussed in terms of its design and system advantages. Areas requiring further research are identified.

Combined TRAF6 Targeting and Proteasome Blockade Has Anti-myeloma and Anti-Bone Resorptive Effects.

PubMed

Chen, Haiming; Li, Mingjie; Sanchez, Eric; Wang, Cathy S; Lee, Tiffany; Soof, Camilia M; Casas, Christian E; Cao, Jasmin; Xie, Colin; Udd, Kyle A; DeCorso, Kevin; Tang, George Y; Spektor, Tanya M; Berenson, James R

2017-05-01

TNF receptor-associated factor 6 (TRAF6) has been implicated in polyubiquitin-mediated IL1R/TLR signaling through activation of IκB kinase (IKK) to regulate the NF-κB and JNK signaling pathways. Here, TRAF6 protein was determined to be overexpressed in bone marrow mononuclear cells (BMMC) from patients with multiple myeloma. TRAF6 expression in BMMCs from patients with progressive disease is significantly elevated as compared with individuals in complete remission, with monoclonal gammopathy of undetermined significance, or healthy subjects. Furthermore, TRAF6 dominant-negative (TRAF6dn) peptides were constructed which specifically reduced TRAF6 signaling and activation of IKK. TRAF6 not only reduced cellular growth but also increased the apoptosis of multiple myeloma tumor cells in a concentration-dependent fashion. Because TRAF6 activates IKK through polyubiquitination, independent of its proteasome activity, a TRAF6dn peptide was combined with the proteasome inhibitors bortezomib or carfilzomib to treat multiple myeloma. Importantly, targeting of TRAF6 in the presence of proteasome inhibition enhanced anti-multiple myeloma effects and also decreased TLR/TRAF6/NF-κB-related signaling. Finally, TRAF6dn dose dependently inhibited osteoclast cell formation from CD14 + monocytes, induced with RANKL and mCSF , and markedly reduced bone resorption in dentin pits. In all, these data demonstrate that blocking TRAF6 signaling has anti-multiple myeloma effects and reduces bone loss. Implications: The ability to target TRAF6 signaling and associated pathways in multiple myeloma suggests a promising new therapeutic approach. Mol Cancer Res; 15(5); 598-609. ©2017 AACR . ©2017 American Association for Cancer Research.

Characterization of Harmonic Signal Acquisition with Parallel Dipole and Multipole Detectors

NASA Astrophysics Data System (ADS)

Park, Sung-Gun; Anderson, Gordon A.; Bruce, James E.

2018-04-01

Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) is a powerful instrument for the study of complex biological samples due to its high resolution and mass measurement accuracy. However, the relatively long signal acquisition periods needed to achieve high resolution can serve to limit applications of FTICR-MS. The use of multiple pairs of detector electrodes enables detection of harmonic frequencies present at integer multiples of the fundamental cyclotron frequency, and the obtained resolving power for a given acquisition period increases linearly with the order of harmonic signal. However, harmonic signal detection also increases spectral complexity and presents challenges for interpretation. In the present work, ICR cells with independent dipole and harmonic detection electrodes and preamplifiers are demonstrated. A benefit of this approach is the ability to independently acquire fundamental and multiple harmonic signals in parallel using the same ions under identical conditions, enabling direct comparison of achieved performance as parameters are varied. Spectra from harmonic signals showed generally higher resolving power than spectra acquired with fundamental signals and equal signal duration. In addition, the maximum observed signal to noise (S/N) ratio from harmonic signals exceeded that of fundamental signals by 50 to 100%. Finally, parallel detection of fundamental and harmonic signals enables deconvolution of overlapping harmonic signals since observed fundamental frequencies can be used to unambiguously calculate all possible harmonic frequencies. Thus, the present application of parallel fundamental and harmonic signal acquisition offers a general approach to improve utilization of harmonic signals to yield high-resolution spectra with decreased acquisition time. [Figure not available: see fulltext.

Multiple-Array Detection, Association and Location of Infrasound and Seismo-Acoustic Events - Utilization of Ground-Truth Information

DTIC Science & Technology

2009-09-30

signals detected by infrasound arrays were discriminated as surface explosions, not earthquakes , and are marked by yellow...velocity, and amplitude of detected signals at each array . Horizontal propagation velocity of infrasound signals , also called celerity, is used not only...REPRINT 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE MULTIPLE- ARRAY DETECTION , ASSOCIATION AND LOCATION OF INFRASOUND AND SEISMO-ACOUSTIC

Impact: a low cost, reconfigurable, digital beamforming common module building block for next generation phased arrays

NASA Astrophysics Data System (ADS)

Paulsen, Lee; Hoffmann, Ted; Fulton, Caleb; Yeary, Mark; Saunders, Austin; Thompson, Dan; Chen, Bill; Guo, Alex; Murmann, Boris

2015-05-01

Phased array systems offer numerous advantages to the modern warfighter in multiple application spaces, including Radar, Electronic Warfare, Signals Intelligence, and Communications. However, a lack of commonality in the underlying technology base for DoD Phased Arrays has led to static systems with long development cycles, slow technology refreshes in response to emerging threats, and expensive, application-specific sub-components. The IMPACT module (Integrated Multi-use Phased Array Common Tile) is a multi-channel, reconfigurable, cost-effective beamformer that provides a common building block for multiple, disparate array applications.

Coding and decoding for code division multiple user communication systems

NASA Technical Reports Server (NTRS)

Healy, T. J.

1985-01-01

A new algorithm is introduced which decodes code division multiple user communication signals. The algorithm makes use of the distinctive form or pattern of each signal to separate it from the composite signal created by the multiple users. Although the algorithm is presented in terms of frequency-hopped signals, the actual transmitter modulator can use any of the existing digital modulation techniques. The algorithm is applicable to error-free codes or to codes where controlled interference is permitted. It can be used when block synchronization is assumed, and in some cases when it is not. The paper also discusses briefly some of the codes which can be used in connection with the algorithm, and relates the algorithm to past studies which use other approaches to the same problem.

Tie2 and Eph Receptor Tyrosine Kinase Activation and Signaling

PubMed Central

Barton, William A.; Dalton, Annamarie C.; Seegar, Tom C.M.; Himanen, Juha P.

2014-01-01

The Eph and Tie cell surface receptors mediate a variety of signaling events during development and in the adult organism. As other receptor tyrosine kinases, they are activated on binding of extracellular ligands and their catalytic activity is tightly regulated on multiple levels. The Eph and Tie receptors display some unique characteristics, including the requirement of ligand-induced receptor clustering for efficient signaling. Interestingly, both Ephs and Ties can mediate different, even opposite, biological effects depending on the specific ligand eliciting the response and on the cellular context. Here we discuss the structural features of these receptors, their interactions with various ligands, as well as functional implications for downstream signaling initiation. The Eph/ephrin structures are already well reviewed and we only provide a brief overview on the initial binding events. We go into more detail discussing the Tie-angiopoietin structures and recognition. PMID:24478383

Modeling of Receptor Tyrosine Kinase Signaling: Computational and Experimental Protocols.

PubMed

Fey, Dirk; Aksamitiene, Edita; Kiyatkin, Anatoly; Kholodenko, Boris N

2017-01-01

The advent of systems biology has convincingly demonstrated that the integration of experiments and dynamic modelling is a powerful approach to understand the cellular network biology. Here we present experimental and computational protocols that are necessary for applying this integrative approach to the quantitative studies of receptor tyrosine kinase (RTK) signaling networks. Signaling by RTKs controls multiple cellular processes, including the regulation of cell survival, motility, proliferation, differentiation, glucose metabolism, and apoptosis. We describe methods of model building and training on experimentally obtained quantitative datasets, as well as experimental methods of obtaining quantitative dose-response and temporal dependencies of protein phosphorylation and activities. The presented methods make possible (1) both the fine-grained modeling of complex signaling dynamics and identification of salient, course-grained network structures (such as feedback loops) that bring about intricate dynamics, and (2) experimental validation of dynamic models.

[Plant signaling peptides. Cysteine-rich peptides].

PubMed

Ostrowski, Maciej; Kowalczyk, Stanisław

2015-01-01

Recent bioinformatic and genetic analyses of several model plant genomes have revealed the existence of a highly abundant group of signaling peptides that are defined as cysteine-rich peptides (CRPs). CRPs are usually in size between 50 and 90 amino acid residues, they are positively charged, and they contain 4-16 cysteine residues that are important for the correct conformational folding. Despite the structural differences among CRP classes, members from each class have striking similarities in their molecular properties and function. The present review presents the recent progress in research on signaling peptides from several families including: EPF/EPFL, SP11/SCR, PrsS, RALF, LURE, and some other peptides belonging to CRP group. There is convincing evidence indicating multiple roles for these CRPs as signaling molecules during the plant life cycle, ranging from stomata development and patterning, self-incompatibility, pollen tube growth and guidance, reproductive processes, and nodule formation.

A fully reconfigurable waveguide Bragg grating for programmable photonic signal processing.

PubMed

Zhang, Weifeng; Yao, Jianping

2018-04-11

Since the discovery of the Bragg's law in 1913, Bragg gratings have become important optical devices and have been extensively used in various systems. In particular, the successful inscription of a Bragg grating in a fiber core has significantly boosted its engineering applications. However, a conventional grating device is usually designed for a particular use, which limits general-purpose applications since its index modulation profile is fixed after fabrication. In this article, we propose to implement a fully reconfigurable grating, which is fast and electrically reconfigurable by field programming. The concept is verified by fabricating an integrated grating on a silicon-on-insulator platform, which is employed as a programmable signal processor to perform multiple signal processing functions including temporal differentiation, microwave time delay, and frequency identification. The availability of ultrafast and reconfigurable gratings opens new avenues for programmable optical signal processing at the speed of light.

Electromyogram whitening for improved classification accuracy in upper limb prosthesis control.

PubMed

Liu, Lukai; Liu, Pu; Clancy, Edward A; Scheme, Erik; Englehart

2013-09-01

Time and frequency domain features of the surface electromyogram (EMG) signal acquired from multiple channels have frequently been investigated for use in controlling upper-limb prostheses. A common control method is EMG-based motion classification. We propose the use of EMG signal whitening as a preprocessing step in EMG-based motion classification. Whitening decorrelates the EMG signal and has been shown to be advantageous in other EMG applications including EMG amplitude estimation and EMG-force processing. In a study of ten intact subjects and five amputees with up to 11 motion classes and ten electrode channels, we found that the coefficient of variation of time domain features (mean absolute value, average signal length and normalized zero crossing rate) was significantly reduced due to whitening. When using these features along with autoregressive power spectrum coefficients, whitening added approximately five percentage points to classification accuracy when small window lengths were considered.

Additive Classical Capacity of Quantum Channels Assisted by Noisy Entanglement.

PubMed

Zhuang, Quntao; Zhu, Elton Yechao; Shor, Peter W

2017-05-19

We give a capacity formula for the classical information transmission over a noisy quantum channel, with separable encoding by the sender and limited resources provided by the receiver's preshared ancilla. Instead of a pure state, we consider the signal-ancilla pair in a mixed state, purified by a "witness." Thus, the signal-witness correlation limits the resource available from the signal-ancilla correlation. Our formula characterizes the utility of different forms of resources, including noisy or limited entanglement assistance, for classical communication. With separable encoding, the sender's signals across multiple channel uses are still allowed to be entangled, yet our capacity formula is additive. In particular, for generalized covariant channels, our capacity formula has a simple closed form. Moreover, our additive capacity formula upper bounds the general coherent attack's information gain in various two-way quantum key distribution protocols. For Gaussian protocols, the additivity of the formula indicates that the collective Gaussian attack is the most powerful.

Early Life Stress Effects on Glucocorticoid—BDNF Interplay in the Hippocampus

PubMed Central

Daskalakis, Nikolaos P.; De Kloet, Edo Ronald; Yehuda, Rachel; Malaspina, Dolores; Kranz, Thorsten M.

2015-01-01

Early life stress (ELS) is implicated in the etiology of multiple psychiatric disorders. Important biological effects of ELS are manifested in stress-susceptible regions of the hippocampus and are partially mediated by long-term effects on glucocorticoid (GC) and/or neurotrophin signaling pathways. GC-signaling mediates the regulation of stress response to maintain homeostasis, while neurotrophin signaling plays a key role in neuronal outgrowth and is crucial for axonal guidance and synaptic integrity. The neurotrophin and GC-signaling pathways co-exist throughout the central nervous system (CNS), particularly in the hippocampus, which has high expression levels of glucocorticoid-receptors (GR) and mineralocorticoid-receptors (MR) as well as brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB). This review addresses the effects of ELS paradigms on GC- and BDNF-dependent mechanisms and their crosstalk in the hippocampus, including potential implications for the pathogenesis of common stress-related disorders. PMID:26635521

Sensitive SERS detection of DNA methyltransferase by target triggering primer generation-based multiple signal amplification strategy.

PubMed

Li, Ying; Yu, Chuanfeng; Han, Huixia; Zhao, Caisheng; Zhang, Xiaoru

2016-07-15

A novel and sensitive surface-enhanced Raman scattering (SERS) method is proposed for the assay of DNA methyltransferase (MTase) activity and evaluation of inhibitors by developing a target triggering primer generation-based multiple signal amplification strategy. By using of a duplex substrate for Dam MTase, two hairpin templates and a Raman probe, multiple signal amplification mode is achieved. Once recognized by Dam MTase, the duplex substrate can be cleaved by Dpn I endonuclease and two primers are released for triggering the multiple signal amplification reaction. Consequently, a wide dynamic range and remarkably high sensitivity are obtained under isothermal conditions. The detection limit is 2.57×10(-4)UmL(-1). This assay exhibits an excellent selectivity and is successfully applied in the screening of inhibitors for Dam MTase. In addition, this novel sensing system is potentially universal as the recognition element can be conveniently designed for other target analytes by changing the substrate of DNA MTase. Copyright © 2016 Elsevier B.V. All rights reserved.

Signal processing and neural network toolbox and its application to failure diagnosis and prognosis

NASA Astrophysics Data System (ADS)

Tu, Fang; Wen, Fang; Willett, Peter K.; Pattipati, Krishna R.; Jordan, Eric H.

2001-07-01

Many systems are comprised of components equipped with self-testing capability; however, if the system is complex involving feedback and the self-testing itself may occasionally be faulty, tracing faults to a single or multiple causes is difficult. Moreover, many sensors are incapable of reliable decision-making on their own. In such cases, a signal processing front-end that can match inference needs will be very helpful. The work is concerned with providing an object-oriented simulation environment for signal processing and neural network-based fault diagnosis and prognosis. In the toolbox, we implemented a wide range of spectral and statistical manipulation methods such as filters, harmonic analyzers, transient detectors, and multi-resolution decomposition to extract features for failure events from data collected by data sensors. Then we evaluated multiple learning paradigms for general classification, diagnosis and prognosis. The network models evaluated include Restricted Coulomb Energy (RCE) Neural Network, Learning Vector Quantization (LVQ), Decision Trees (C4.5), Fuzzy Adaptive Resonance Theory (FuzzyArtmap), Linear Discriminant Rule (LDR), Quadratic Discriminant Rule (QDR), Radial Basis Functions (RBF), Multiple Layer Perceptrons (MLP) and Single Layer Perceptrons (SLP). Validation techniques, such as N-fold cross-validation and bootstrap techniques, are employed for evaluating the robustness of network models. The trained networks are evaluated for their performance using test data on the basis of percent error rates obtained via cross-validation, time efficiency, generalization ability to unseen faults. Finally, the usage of neural networks for the prediction of residual life of turbine blades with thermal barrier coatings is described and the results are shown. The neural network toolbox has also been applied to fault diagnosis in mixed-signal circuits.

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

A novel stilbene-like compound that inhibits melanoma growth by regulating melanocyte differentiation and proliferation.

PubMed

Stueven, Noah A; Schlaeger, Nicholas M; Monte, Aaron P; Hwang, Sheng-Ping L; Huang, Cheng-Chen

2017-12-15

Melanoma is the most aggressive form of skin cancer. Current challenges to melanoma therapy include the adverse effects from immunobiologics, resistance to drugs targeting the MAPK pathway, intricate interaction of many signal pathways, and cancer heterogeneity. Thus combinational therapy with drugs targeting multiple signaling pathways becomes a new promising therapy. Here, we report a family of stilbene-like compounds called A11 that can inhibit melanoma growth in both melanoma-forming zebrafish embryos and mouse melanoma cells. The growth inhibition by A11 is a result of mitosis reduction but not apoptosis enhancement. Meanwhile, A11 activates both MAPK and Akt signaling pathways. Many A11-treated mouse melanoma cells exhibit morphological changes and resemble normal melanocytes. Furthermore, we found that A11 causes down-regulation of melanocyte differentiation genes, including Pax3 and MITF. Together, our results suggest that A11 could be a new melanoma therapeutic agent by inhibiting melanocyte differentiation and proliferation. Copyright © 2017 Elsevier Inc. All rights reserved.

Is the canonical RAF-MEK-ERK signaling pathway a therapeutic target in SCLC?

PubMed Central

Cristea, Sandra; Sage, Julien

2017-01-01

The activity of the RAF-MEK-ERK signaling pathway is critical for the proliferation of normal and cancerous cells. Oncogenic mutations driving the development of lung adenocarcinoma often activate this signaling pathway. In contrast, pathway activity levels and their biological roles are not well established in small cell lung cancer (SCLC), a fast-growing neuroendocrine lung cancer subtype. Here we discuss the function of the RAF-MEK-ERK kinase pathway and the mechanisms leading to its activation in SCLC cells. In particular, we argue that activation of this pathway may be beneficial to the survival, proliferation and spread of SCLC cells in response to multiple stimuli. We also consider evidence that high levels of RAF-MEK-ERK pathway activity may be detrimental to SCLC tumors, including in part by interfering with their neuroendocrine fate. Based on these observations, we examine when small molecules targeting kinases in the RAF-MEK-ERK pathway may be useful therapeutically in SCLC patients, including in combination with other therapeutic agents. PMID:27133774

Ubiquitination of the Dishevelled DIX domain blocks its head-to-tail polymerization

PubMed Central

Madrzak, Julia; Fiedler, Marc; Johnson, Christopher M.; Ewan, Richard; Knebel, Axel; Bienz, Mariann; Chin, Jason W.

2015-01-01

Dishevelled relays Wnt signals from the plasma membrane to different cytoplasmic effectors. Its signalling activity depends on its DIX domain, which undergoes head-to-tail polymerization to assemble signalosomes. The DIX domain is ubiquitinated in vivo at multiple lysines, which can be antagonized by various deubiquitinases (DUBs) including the CYLD tumour suppressor that attenuates Wnt signalling. Here, we generate milligram quantities of pure human Dvl2 DIX domain mono-ubiquitinated at two lysines (K54 and K58) by genetically encoded orthogonal protection with activated ligation (GOPAL), to investigate their effect on DIX polymerization. We show that the ubiquitination of DIX at K54 blocks its polymerization in solution, whereas DIX58-Ub remains oligomerization-competent. DUB profiling identified 28 DUBs that cleave DIX-ubiquitin conjugates, half of which prefer, or are specific for, DIX54-Ub, including Cezanne and CYLD. These DUBs thus have the potential to promote Dvl polymerization and signalosome formation, rather than antagonize it as previously thought for CYLD. PMID:25907794

Signal Diversity of Receptor for Advanced Glycation End Products.

PubMed

Sakaguchi, Masakiyo; Kinoshita, Rie; Putranto, Endy Widya; Ruma, I Made Winarsa; Sumardika, I Wayan; Youyi, Chen; Tomonobu, Naoko; Yamamoto, Ken-Ichi; Murata, Hitoshi

2017-12-01

The receptor for advanced glycation end products (RAGE) is involved in inflammatory pathogenesis. It functions as a receptor to multiple ligands such as AGEs, HMGB1 and S100 proteins, activating multiple intracellular signaling pathways with each ligand binding. The molecular events by which ligand-activated RAGE controls diverse signaling are not well understood, but some progress was made recently. Accumulating evidence revealed that RAGE has multiple binding partners within the cytoplasm and on the plasma membrane. It was first pointed out in 2008 that RAGE's cytoplasmic tail is able to recruit Diaphanous-1 (Dia-1), resulting in the acquisition of increased cellular motility through Rac1/Cdc42 activation. We also observed that within the cytosol, RAGE's cytoplasmic tail behaves similarly to a Toll-like receptor (TLR4)-TIR domain, interacting with TIRAP and MyD88 adaptor molecules that in turn activate multiple downstream signals. Subsequent studies demonstrated the presence of an alternative adaptor molecule, DAP10, on the plasma membrane. The coupling of RAGE with DAP10 is critical for enhancing the RAGE-mediated survival signal. Interestingly, RAGE interaction on the membrane was not restricted to DAP10 alone. The chemotactic G-protein-coupled receptors (GPCRs) formyl peptide receptors1 and 2 (FPR1 and FPR2) also interacted with RAGE on the plasma membrane. Binding interaction between leukotriene B4 receptor 1 (BLT1) and RAGE was also demonstrated. All of the interactions affected the RAGE signal polarity. These findings indicate that functional interactions between RAGE and various molecules within the cytoplasmic area or on the membrane area coordinately regulate multiple ligand-mediated RAGE responses, leading to typical cellular phenotypes in several pathological settings. Here we review RAGE's signaling diversity, to contribute to the understanding of the elaborate functions of RAGE in physiological and pathological contexts.

TEAD1 mediates the oncogenic activities of Hippo-YAP1 signaling in osteosarcoma.

PubMed

Chai, Jiwei; Xu, Shijie; Guo, Fengbo

2017-06-24

Hippo signaling pathway is an evolutionarily conserved developmental network that governs the downstream transcriptional co-activators, YAP and TAZ, which bind to and activate the output of TEADs that responsible for cell proliferation, apoptosis, and stem cell self renewal. Emerging evidence has shown the tumor suppressor properties of Hippo signaling. However, limited knowledge is available concerning the downstream transcription factors of Hippo pathway in osteosarcoma (OS). In this study, we demonstrated that TEAD1 was the major transcription factor of Hippo signaling pathway in OS. Genetic silencing of TEAD1 suppressed multiple malignant phenotypes of OS cells including cell proliferation, apoptosis resistance, and invasive potential. Mechanistically, we showed that TEAD1 largely exerted its transcriptional control of its functional targets, PTGS2 and CYR61. Collectively, this work identifies the YAP1/TEAD1 complex as the representative dysregulated profile of Hippo signaling in OS and provides proof-of-principle that targeting TEAD1 may be a therapeutic strategy of osteosarcoma. Copyright © 2017. Published by Elsevier Inc.

A MUSIC-based method for SSVEP signal processing.

PubMed

Chen, Kun; Liu, Quan; Ai, Qingsong; Zhou, Zude; Xie, Sheng Quan; Meng, Wei

2016-03-01

The research on brain computer interfaces (BCIs) has become a hotspot in recent years because it offers benefit to disabled people to communicate with the outside world. Steady state visual evoked potential (SSVEP)-based BCIs are more widely used because of higher signal to noise ratio and greater information transfer rate compared with other BCI techniques. In this paper, a multiple signal classification based method was proposed for multi-dimensional SSVEP feature extraction. 2-second data epochs from four electrodes achieved excellent accuracy rates including idle state detection. In some asynchronous mode experiments, the recognition accuracy reached up to 100%. The experimental results showed that the proposed method attained good frequency resolution. In most situations, the recognition accuracy was higher than canonical correlation analysis, which is a typical method for multi-channel SSVEP signal processing. Also, a virtual keyboard was successfully controlled by different subjects in an unshielded environment, which proved the feasibility of the proposed method for multi-dimensional SSVEP signal processing in practical applications.

Sonic Hedgehog promotes proliferation of Notch-dependent monociliated choroid plexus tumour cells

PubMed Central

Li, Li; Grausam, Katie B.; Wang, Jun; Lun, Melody P.; Ohli, Jasmin; Lidov, Hart G. W.; Calicchio, Monica L.; Zeng, Erliang; Salisbury, Jeffrey L.; Wechsler-Reya, Robert J.; Lehtinen, Maria K.; Schüller, Ulrich; Zhao, Haotian

2016-01-01

Aberrant Notch signaling has been linked to many cancers including choroid plexus (CP) tumours, a group of rare and predominantly pediatric brain neoplasms. We developed animal models of CP tumours by inducing sustained expression of Notch1 that recapitulate properties of human CP tumours with aberrant NOTCH signaling. Whole transcriptome and functional analyses showed that tumour cell proliferation is associated with Sonic Hedgehog (Shh) in the tumour microenvironment. Unlike CP epithelial cells, which have multiple primary cilia, tumour cells possess a solitary primary cilium as a result of Notch-mediated suppression of multiciliate diffferentiation. A Shh-driven signaling cascade in the primary cilium occurs in tumour cells but not in epithelial cells. Lineage studies show that CP tumours arise from mono-ciliated progenitors in the roof plate characterized by elevated Notch signaling. Abnormal SHH signaling and distinct ciliogenesis are detected in human CP tumours, suggesting SHH pathway and cilia differentiation as potential therapeutic avenues. PMID:26999738

Specification of Drosophila Corpora Cardiaca Neuroendocrine Cells from Mesoderm Is Regulated by Notch Signaling

PubMed Central

Park, Sangbin; Bustamante, Erika L.; Antonova, Julie; McLean, Graeme W.; Kim, Seung K.

2011-01-01

Drosophila neuroendocrine cells comprising the corpora cardiaca (CC) are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells. Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland, the genetic regulation of CC development is poorly understood. From a genetic screen, we identified multiple novel regulators of CC development, including Notch signaling factors. Our studies demonstrate that the disruption of Notch signaling can lead to the expansion of CC cells. Live imaging demonstrates localized emergence of extra precursor cells as the basis of CC expansion in Notch mutants. Contrary to a recent report, we unexpectedly found that CC cells originate from head mesoderm. We show that Tinman expression in head mesoderm is regulated by Notch signaling and that the combination of Daughterless and Tinman is sufficient for ectopic CC specification in mesoderm. Understanding the cellular, genetic, signaling, and transcriptional basis of CC cell specification and expansion should accelerate discovery of molecular mechanisms regulating ontogeny of organs that control metabolism. PMID:21901108

Non-destructive testing of full-length bonded rock bolts based on HHT signal analysis

NASA Astrophysics Data System (ADS)

Shi, Z. M.; Liu, L.; Peng, M.; Liu, C. C.; Tao, F. J.; Liu, C. S.

2018-04-01

Full-length bonded rock bolts are commonly used in mining, tunneling and slope engineering because of their simple design and resistance to corrosion. However, the length of a rock bolt and grouting quality do not often meet the required design standards in practice because of the concealment and complexity of bolt construction. Non-destructive testing is preferred when testing a rock bolt's quality because of the convenience, low cost and wide detection range. In this paper, a signal analysis method for the non-destructive sound wave testing of full-length bonded rock bolts is presented, which is based on the Hilbert-Huang transform (HHT). First, we introduce the HHT analysis method to calculate the bolt length and identify defect locations based on sound wave reflection test signals, which includes decomposing the test signal via empirical mode decomposition (EMD), selecting the intrinsic mode functions (IMF) using the Pearson Correlation Index (PCI) and calculating the instantaneous phase and frequency via the Hilbert transform (HT). Second, six model tests are conducted using different grouting defects and bolt protruding lengths to verify the effectiveness of the HHT analysis method. Lastly, the influence of the bolt protruding length on the test signal, identification of multiple reflections from defects, bolt end and protruding end, and mode mixing from EMD are discussed. The HHT analysis method can identify the bolt length and grouting defect locations from signals that contain noise at multiple reflected interfaces. The reflection from the long protruding end creates an irregular test signal with many frequency peaks on the spectrum. The reflections from defects barely change the original signal because they are low energy, which cannot be adequately resolved using existing methods. The HHT analysis method can identify reflections from the long protruding end of the bolt and multiple reflections from grouting defects based on mutations in the instantaneous frequency, which makes weak reflections more noticeable. The mode mixing phenomenon is observed in several tests, but this does not markedly affect the identification results due to the simple medium in bolt tests. The mode mixing can be reduced by ensemble EMD (EEMD) or complete ensemble EMD with adaptive noise (CEEMDAN), which are powerful tools to used analyze the test signal in a complex medium and may play an important role in future studies. The HHT bolt signal analysis method is a self-adaptive and automatic process, which can be programed as analysis software and will make bolt tests more convenient in practice.

NASA's next generation all-digital deep space network breadboard receiver

NASA Technical Reports Server (NTRS)

Hinedi, Sami

1993-01-01

This paper describes the breadboard advanced receiver (ARX) that is currently being built for future use in NASA's deep space network (DSN). This receiver has unique requirements in having to operate with very weak signals from deep space probes and provide high quality telemetry and tracking data. The hybrid analog/digital receiver performs multiple functions including carrier, subcarrier and symbol synchronization. Tracking can be achieved for either residual, suppressed or hybrid carriers and for both sinusoidal and square wave subcarriers. System requirements are specified and a functional description of the ARX is presented. The various digital signal processing algorithms used are also discussed and illustrated with block diagrams. Other functions such as time tagged Doppler extraction and monitor/control are also discussed including acquisition algorithms and lock detection schemes.

Discrete Notch signaling requirements in the specification of hematopoietic stem cells

PubMed Central

Kim, Albert D; Melick, Chase H; Clements, Wilson K; Stachura, David L; Distel, Martin; Panáková, Daniela; MacRae, Calum; Mork, Lindsey A; Crump, J Gage; Traver, David

2014-01-01

Hematopoietic stem cells (HSCs) require multiple molecular inputs for proper specification, including activity of the Notch signaling pathway. A requirement for the Notch1 and dispensability of the Notch2 receptor has been demonstrated in mice, but the role of the remaining Notch receptors has not been investigated. Here, we demonstrate that three of the four Notch receptors are independently required for the specification of HSCs in the zebrafish. The orthologues of the murine Notch1 receptor, Notch1a and Notch1b, are each required intrinsically to fate HSCs, just prior to their emergence from aortic hemogenic endothelium. By contrast, the Notch3 receptor is required earlier within the developing somite to regulate HSC emergence in a non-cell-autonomous manner. Epistatic analyses demonstrate that Notch3 function lies downstream of Wnt16, which is required for HSC specification through its regulation of two Notch ligands, dlc and dld. Collectively, these findings demonstrate for the first time that multiple Notch signaling inputs are required to specify HSCs and that Notch3 performs a novel role within the somite to regulate the neighboring precursors of hemogenic endothelium. PMID:25230933

Cinnamon extract regulates plasma levels of adipose-derived factors and expression of multiple genes related to carbohydrate metabolism and lipogenesis in adipose tissue of fructose-fed rats

USDA-ARS?s Scientific Manuscript database

We reported previously that a dietary cinnamon extract (CE) improves systemic insulin sensitivity and dyslipidemia by enhancing insulin signaling. In the present study, we examined the effects of CE on several biomarkers including plasma levels of adipose-derived adipokines, and the potential molec...

Reversible metronidazole-induced cerebellar toxicity in a multiple transplant recipient.

PubMed

Graves, Tracey D; Condon, Marie; Loucaidou, Marina; Perry, Richard J

2009-10-15

Metronidazole-induced central nervous system (CNS) toxicity causes a spectrum of neurological symptoms including ataxia, encephalopathy and peripheral neuropathy. It is associated with characteristic MRI changes of high signal intensity in the dentate nuclei. Given the increasing use of metronidazole, it is import to recognise this drug as a cause of ataxia, as it is entirely reversible on drug withdrawal.

Ibrutinib targets microRNA-21 in multiple myeloma cells by inhibiting NF-κB and STAT3.

PubMed

Ma, Jing; Gong, Wei; Liu, Su; Li, Qian; Guo, Mengzheng; Wang, Jinhan; Wang, Suying; Chen, Naiyao; Wang, Yafei; Liu, Qiang; Zhao, Hui

2018-01-01

The oncogenic microRNA-21 contributes to the pathogenesis of multiple myeloma. Ibrutinib (also referred to as PCI-32765), an inhibitor of Bruton's tyrosine kinase, while its effects on multiple myeloma have not been well described. Here, we show that microRNA-21 is an oncogenic marker closely linked with progression of multiple myeloma. Moreover, ibrutinib attenuates microRNA-21 expression in multiple myeloma cells by inhibiting nuclear factor-κB and signal transducer and activator of transcription 3 signaling pathways. Taken together, our results suggest that ibrutinib is a promising potential treatment for multiple myeloma. Further investigation of mechanisms of ibrutinib function in multiple myeloma will be necessary to evaluate its use as a novel multiple myeloma treatment.

The osteoblastic niche in the context of multiple myeloma.

PubMed

Toscani, Denise; Bolzoni, Marina; Accardi, Fabrizio; Aversa, Franco; Giuliani, Nicola

2015-01-01

The osteoblastic niche has a critical role in the regulation of hemopoietic stem cell (HSC) quiescence and self-renewal and in the support of hematopoiesis. Several mechanisms are involved in the crosstalk between stem cells and osteoblasts, including soluble cytokines, adhesion molecules, and signal pathways such as the wingless-Int (Wnt), Notch, and parathyroid hormone pathways. According to the most recent evidence, there is an overlap between osteoblastic and perivascular niches that affects HSC function involving mesenchymal stromal and endothelial cells and a gradient of oxygen regulated by hypoxia inducible factor (HIF)-1α. Derived from plasma cells, multiple myeloma (MM) is a hematopoietic malignancy characterized by a peculiar dependency on the bone microenvironment. Quiescent MM cells may reside in the osteoblastic niche for protection from apoptotic stimuli; in turn, MM cells suppress osteoblast formation and function, leading to impairment of bone formation and the development of osteolytic lesions. Several recent studies have investigated the mechanisms involved in the relationship between osteoblasts and MM cells and identified potential therapeutic targets in the osteoblastic niche, including the HIF-1α, Runx2, and Wnt (both canonical and noncanonical) signaling pathways. © 2014 New York Academy of Sciences.

Sex and hedgehog: roles of genes in the hedgehog signaling pathway in mammalian sexual differentiation.

PubMed

Franco, Heather L; Yao, Humphrey H-C

2012-01-01

The chromosome status of the mammalian embryo initiates a multistage process of sexual development in which the bipotential reproductive system establishes itself as either male or female. These events are governed by intricate cell-cell and interorgan communication that is regulated by multiple signaling pathways. The hedgehog signaling pathway was originally identified for its key role in the development of Drosophila, but is now recognized as a critical developmental regulator in many species, including humans. In addition to its developmental roles, the hedgehog signaling pathway also modulates adult organ function, and misregulation of this pathway often leads to diseases, such as cancer. The hedgehog signaling pathway acts through its morphogenetic ligands that signal from ligand-producing cells to target cells over a specified distance. The target cells then respond in a graded manner based on the concentration of the ligands that they are exposed to. Through this unique mechanism of action, the hedgehog signaling pathway elicits cell fate determination, epithelial-mesenchymal interactions, and cellular homeostasis. Here, we review current findings on the roles of hedgehog signaling in the sexually dimorphic development of the reproductive organs with an emphasis on mammals and comparative evidence in other species.

High channel count microphone array accurately and precisely localizes ultrasonic signals from freely-moving mice.

PubMed

Warren, Megan R; Sangiamo, Daniel T; Neunuebel, Joshua P

2018-03-01

An integral component in the assessment of vocal behavior in groups of freely interacting animals is the ability to determine which animal is producing each vocal signal. This process is facilitated by using microphone arrays with multiple channels. Here, we made important refinements to a state-of-the-art microphone array based system used to localize vocal signals produced by freely interacting laboratory mice. Key changes to the system included increasing the number of microphones as well as refining the methodology for localizing and assigning vocal signals to individual mice. We systematically demonstrate that the improvements in the methodology for localizing mouse vocal signals led to an increase in the number of signals detected as well as the number of signals accurately assigned to an animal. These changes facilitated the acquisition of larger and more comprehensive data sets that better represent the vocal activity within an experiment. Furthermore, this system will allow more thorough analyses of the role that vocal signals play in social communication. We expect that such advances will broaden our understanding of social communication deficits in mouse models of neurological disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

On-Line Multi-Damage Scanning Spatial-Wavenumber Filter Based Imaging Method for Aircraft Composite Structure.

PubMed

Ren, Yuanqiang; Qiu, Lei; Yuan, Shenfang; Bao, Qiao

2017-05-11

Structural health monitoring (SHM) of aircraft composite structure is helpful to increase reliability and reduce maintenance costs. Due to the great effectiveness in distinguishing particular guided wave modes and identifying the propagation direction, the spatial-wavenumber filter technique has emerged as an interesting SHM topic. In this paper, a new scanning spatial-wavenumber filter (SSWF) based imaging method for multiple damages is proposed to conduct on-line monitoring of aircraft composite structures. Firstly, an on-line multi-damage SSWF is established, including the fundamental principle of SSWF for multiple damages based on a linear piezoelectric (PZT) sensor array, and a corresponding wavenumber-time imaging mechanism by using the multi-damage scattering signal. Secondly, through combining the on-line multi-damage SSWF and a PZT 2D cross-shaped array, an image-mapping method is proposed to conduct wavenumber synthesis and convert the two wavenumber-time images obtained by the PZT 2D cross-shaped array to an angle-distance image, from which the multiple damages can be directly recognized and located. In the experimental validation, both simulated multi-damage and real multi-damage introduced by repeated impacts are performed on a composite plate structure. The maximum localization error is less than 2 cm, which shows good performance of the multi-damage imaging method. Compared with the existing spatial-wavenumber filter based damage evaluation methods, the proposed method requires no more than the multi-damage scattering signal and can be performed without depending on any wavenumber modeling or measuring. Besides, this method locates multiple damages by imaging instead of the geometric method, which helps to improve the signal-to-noise ratio. Thus, it can be easily applied to on-line multi-damage monitoring of aircraft composite structures.

Super-resolution photoacoustic microscopy using joint sparsity

NASA Astrophysics Data System (ADS)

Burgholzer, P.; Haltmeier, M.; Berer, T.; Leiss-Holzinger, E.; Murray, T. W.

2017-07-01

We present an imaging method that uses the random optical speckle patterns that naturally emerge as light propagates through strongly scattering media as a structured illumination source for photoacoustic imaging. Our approach, termed blind structured illumination photoacoustic microscopy (BSIPAM), was inspired by recent work in fluorescence microscopy where super-resolution imaging was demonstrated using multiple unknown speckle illumination patterns. We extend this concept to the multiple scattering domain using photoacoustics (PA), with the speckle pattern serving to generate ultrasound. The optical speckle pattern that emerges as light propagates through diffuse media provides structured illumination to an object placed behind a scattering wall. The photoacoustic signal produced by such illumination is detected using a focused ultrasound transducer. We demonstrate through both simulation and experiment, that by acquiring multiple photoacoustic images, each produced by a different random and unknown speckle pattern, an image of an absorbing object can be reconstructed with a spatial resolution far exceeding that of the ultrasound transducer. We experimentally and numerically demonstrate a gain in resolution of more than a factor of two by using multiple speckle illuminations. The variations in the photoacoustic signals generated with random speckle patterns are utilized in BSIPAM using a novel reconstruction algorithm. Exploiting joint sparsity, this algorithm is capable of reconstructing the absorbing structure from measured PA signals with a resolution close to the speckle size. Another way to excite random excitation for photoacoustic imaging are small absorbing particles, including contrast agents, which flow through small vessels. For such a set-up, the joint-sparsity is generated by the fact that all the particles move in the same vessels. Structured illumination in that case is not necessary.

On-Line Multi-Damage Scanning Spatial-Wavenumber Filter Based Imaging Method for Aircraft Composite Structure

PubMed Central

Ren, Yuanqiang; Qiu, Lei; Yuan, Shenfang; Bao, Qiao

2017-01-01

Structural health monitoring (SHM) of aircraft composite structure is helpful to increase reliability and reduce maintenance costs. Due to the great effectiveness in distinguishing particular guided wave modes and identifying the propagation direction, the spatial-wavenumber filter technique has emerged as an interesting SHM topic. In this paper, a new scanning spatial-wavenumber filter (SSWF) based imaging method for multiple damages is proposed to conduct on-line monitoring of aircraft composite structures. Firstly, an on-line multi-damage SSWF is established, including the fundamental principle of SSWF for multiple damages based on a linear piezoelectric (PZT) sensor array, and a corresponding wavenumber-time imaging mechanism by using the multi-damage scattering signal. Secondly, through combining the on-line multi-damage SSWF and a PZT 2D cross-shaped array, an image-mapping method is proposed to conduct wavenumber synthesis and convert the two wavenumber-time images obtained by the PZT 2D cross-shaped array to an angle-distance image, from which the multiple damages can be directly recognized and located. In the experimental validation, both simulated multi-damage and real multi-damage introduced by repeated impacts are performed on a composite plate structure. The maximum localization error is less than 2 cm, which shows good performance of the multi-damage imaging method. Compared with the existing spatial-wavenumber filter based damage evaluation methods, the proposed method requires no more than the multi-damage scattering signal and can be performed without depending on any wavenumber modeling or measuring. Besides, this method locates multiple damages by imaging instead of the geometric method, which helps to improve the signal-to-noise ratio. Thus, it can be easily applied to on-line multi-damage monitoring of aircraft composite structures. PMID:28772879

Design and Implementation of Multi-Input Adaptive Signal Extractions.

DTIC Science & Technology

1982-09-01

deflected gradient) algorithm requiring only N+ l multiplications per adaptation step. Additional quantization is introduced to eliminate all multiplications...noise cancellation for intermittent-signal applications," IEEE Trans. Information Theory, Vol. IT-26. Nov. 1980, pp. 746-750. 1-2 J. Kazakoff and W. A...cancellation," Proc. IEEE, July 1981, Vol. 69, pp. 846-847. *I-10 P. L . Kelly and W. A. Gardner, "Pilot-Directed Adaptive Signal Extraction," Dept. of

Methotrexate Is a JAK/STAT Pathway Inhibitor

PubMed Central

Thomas, Sally; Fisher, Katherine H.; Snowden, John A.; Danson, Sarah J.; Brown, Stephen; Zeidler, Martin P.

2015-01-01

Background The JAK/STAT pathway transduces signals from multiple cytokines and controls haematopoiesis, immunity and inflammation. In addition, pathological activation is seen in multiple malignancies including the myeloproliferative neoplasms (MPNs). Given this, drug development efforts have targeted the pathway with JAK inhibitors such as ruxolitinib. Although effective, high costs and side effects have limited its adoption. Thus, a need for effective low cost treatments remains. Methods & Findings We used the low-complexity Drosophila melanogaster pathway to screen for small molecules that modulate JAK/STAT signalling. This screen identified methotrexate and the closely related aminopterin as potent suppressors of STAT activation. We show that methotrexate suppresses human JAK/STAT signalling without affecting other phosphorylation-dependent pathways. Furthermore, methotrexate significantly reduces STAT5 phosphorylation in cells expressing JAK2 V617F, a mutation associated with most human MPNs. Methotrexate acts independently of dihydrofolate reductase (DHFR) and is comparable to the JAK1/2 inhibitor ruxolitinib. However, cells treated with methotrexate still retain their ability to respond to physiological levels of the ligand erythropoietin. Conclusions Aminopterin and methotrexate represent the first chemotherapy agents developed and act as competitive inhibitors of DHFR. Methotrexate is also widely used at low doses to treat inflammatory and immune-mediated conditions including rheumatoid arthritis. In this low-dose regime, folate supplements are given to mitigate side effects by bypassing the biochemical requirement for DHFR. Although independent of DHFR, the mechanism-of-action underlying the low-dose effects of methotrexate is unknown. Given that multiple pro-inflammatory cytokines signal through the pathway, we suggest that suppression of the JAK/STAT pathway is likely to be the principal anti-inflammatory and immunosuppressive mechanism-of-action of low-dose methotrexate. In addition, we suggest that patients with JAK/STAT-associated haematological malignancies may benefit from low-dose methotrexate treatments. While the JAK1/2 inhibitor ruxolitinib is effective, a £43,200 annual cost precludes widespread adoption. With an annual methotrexate cost of around £32, our findings represent an important development with significant future potential. PMID:26131691

Assessing signal-to-noise in quantitative proteomics: multivariate statistical analysis in DIGE experiments.

PubMed

Friedman, David B

2012-01-01

All quantitative proteomics experiments measure variation between samples. When performing large-scale experiments that involve multiple conditions or treatments, the experimental design should include the appropriate number of individual biological replicates from each condition to enable the distinction between a relevant biological signal from technical noise. Multivariate statistical analyses, such as principal component analysis (PCA), provide a global perspective on experimental variation, thereby enabling the assessment of whether the variation describes the expected biological signal or the unanticipated technical/biological noise inherent in the system. Examples will be shown from high-resolution multivariable DIGE experiments where PCA was instrumental in demonstrating biologically significant variation as well as sample outliers, fouled samples, and overriding technical variation that would not be readily observed using standard univariate tests.

Ambient temperature signalling in plants.

PubMed

Wigge, Philip A

2013-10-01

Plants are exposed to daily and seasonal fluctuations in temperature. Within the 'ambient' temperature range (about 12-27°C for Arabidopsis) temperature differences have large effects on plant growth and development, disease resistance pathways and the circadian clock without activating temperature stress pathways. It is this developmental sensing and response to non-stressful temperatures that will be covered in this review. Recent advances have revealed key players in mediating temperature signals. The bHLH transcription factor PHYTOCHROME INTERACTING FACTOR4 (PIF4) has been shown to be a hub for multiple responses to warmer temperature in Arabidopsis, including flowering and hypocotyl elongation. Changes in chromatin state are involved in transmitting temperature signals to the transcriptome. Determining the precise mechanisms of temperature perception represents an exciting goal for the field. Copyright © 2013 Elsevier Ltd. All rights reserved.

Quantifying oncogenic phosphotyrosine signaling networks through systems biology.

PubMed

Del Rosario, Amanda M; White, Forest M

2010-02-01

Pathways linking oncogenic mutations to increased proliferative or migratory capacity are poorly characterized, yet provide potential targets for therapeutic intervention. As tyrosine phosphorylation signaling networks are known to mediate proliferation and migration, and frequently go awry in cancers, a comprehensive understanding of these networks in normal and diseased states is warranted. To this end, recent advances in mass spectrometry, protein microarrays, and computational algorithms provide insight into various aspects of the network including phosphotyrosine identification, analysis of kinase/phosphatase substrates, and phosphorylation-mediated protein-protein interactions. Here we detail technological advances underlying these system-level approaches and give examples of their applications. By combining multiple approaches, it is now possible to quantify changes in the phosphotyrosine signaling network with various oncogenic mutations, thereby unveiling novel therapeutic targets. Copyright 2009 Elsevier Ltd. All rights reserved.

Remote Optical Control of an Optical Flip-Flop

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

Maywar, D.N.; Solomon, K.P.; Agrawal, G.P.

2007-11-01

We experimentally demonstrate control of a holding-beam–enabled optical flip-flop by means of optical signals that act in a remote fashion. These optical-control signals vary the holding-beam power by means of cross-gain modulation within a remotely located semiconductor optical amplifier (SOA). The power-modulated holding beam then travels through a resonant-type SOA, where flip-flop action occurs as the holding-beam power falls above and below the switching thresholds of the bistable hysteresis. Control is demonstrated using submilliwatt pulses whose wavelengths are not restricted to the vicinity of the holding beam. Benefits of remote control include the potential for controlling multiple flip-flops with amore » single pair of optical signals and for realizing all-optical control of any holding-beam–enabled flip-flop.« less

Up-regulation of OLR1 expression by TBC1D3 through activation of TNFα/NF-κB pathway promotes the migration of human breast cancer cells.

PubMed

Wang, Bei; Zhao, Huzi; Zhao, Lei; Zhang, Yongchen; Wan, Qing; Shen, Yong; Bu, Xiaodong; Wan, Meiling; Shen, Chuanlu

2017-11-01

Metastatic spread of cancer cells is the most life-threatening aspect of breast cancer and involves multiple steps including cell migration. We recently found that the TBC1D3 oncogene promotes the migration of breast cancer cells, and its interaction with CaM enhances the effects of TBC1D3. However, little is known regarding the mechanism by which TBC1D3 induces the migration of cancer cells. Here, we demonstrated that TBC1D3 stimulated the expression of oxidized low density lipoprotein receptor 1 (OLR1), a stimulator of cell migration, in breast cancer cells at the transcriptional level. Depletion of OLR1 by siRNAs or down-regulation of OLR1 expression using pomalidomide, a TNFα inhibitor, significantly decreased TBC1D3-induced migration of these cells. Notably, TBC1D3 overexpression activated NF-κB, a major effector of TNFα signaling, while inhibition of TNFα signaling suppressed the effects of TBC1D3. Consistent with this, NF-κB inhibition using its specific inhibitor caffeic acid phenethyl ester decreased both TBC1D3-induced OLR1 expression and cell migration, suggesting a critical role for TNFα/NF-κB signaling in TBC1D3-induced migration of breast cancer cells. Mechanistically, TBC1D3 induced activation of this signaling pathway on multiple levels, including by increasing the release of TNFα, elevating the transcription of TNFR1, TRAF1, TRAF5 and TRAF6, and decreasing the degradation of TNFR1. In summary, these studies identify the TBC1D3 oncogene as a novel regulator of TNFα/NF-κB signaling that mediates this oncogene-induced migration of human breast cancer cells by up-regulating OLR1. Copyright © 2017 Elsevier B.V. All rights reserved.

Multiple cues produced by a robotic fish modulate aggressive behaviour in Siamese fighting fishes.

PubMed

Romano, Donato; Benelli, Giovanni; Donati, Elisa; Remorini, Damiano; Canale, Angelo; Stefanini, Cesare

2017-07-05

The use of robotics to establish social interactions between animals and robots, represents an elegant and innovative method to investigate animal behaviour. However, robots are still underused to investigate high complex and flexible behaviours, such as aggression. Here, Betta splendens was tested as model system to shed light on the effect of a robotic fish eliciting aggression. We evaluated how multiple signal systems, including a light stimulus, affect aggressive responses in B. splendens. Furthermore, we conducted experiments to estimate if aggressive responses were triggered by the biomimetic shape of fish replica, or whether any intruder object was effective as well. Male fishes showed longer and higher aggressive displays as puzzled stimuli from the fish replica increased. When the fish replica emitted its full sequence of cues, the intensity of aggression exceeded even that produced by real fish opponents. Fish replica shape was necessary for conspecific opponent perception, evoking significant aggressive responses. Overall, this study highlights that the efficacy of an artificial opponent eliciting aggressive behaviour in fish can be boosted by exposure to multiple signals. Optimizing the cue combination delivered by the robotic fish replica may be helpful to predict escalating levels of aggression.

Neuregulin in Cardiovascular Development and Disease

PubMed Central

Odiete, Oghenerukevwe; Hill, Michael F.; Sawyer, Douglas B.

2013-01-01

Studies in genetically modified mice have demonstrated that neuregulin-1 (NRG-1), along with the erythroblastic leukemia viral oncogene homolog (ErbB) 2, 3, and 4 receptor tyrosine kinases, is necessary for multiple aspects of cardiovascular development. These observations stimulated in vitro and in vivo animal studies, implicating NRG-1/ErbB signaling in the regulation of cardiac cell biology throughout life. Cardiovascular effects of ErbB2-targeted cancer therapies provide evidence in humans that ErbB signaling plays a role in the maintenance of cardiac function. These and other studies suggest a conceptual model in which a key function of NRG-1/ErbB signaling is to mediate adaptations of the heart to physiological and pathological stimuli through activation of intracellular kinase cascades that regulate tissue plasticity. Recent work implicates NRG-1/ErbB signaling in the regulation of multiple aspects of cardiovascular biology, including angiogenesis, blood pressure, and skeletal muscle responses to exercise. The therapeutic potential of recombinant NRG-1 as a potential treatment for heart failure has been demonstrated in animal models and is now being explored in clinical studies. NRG-1 is found in human serum and plasma, and it correlates with some clinical parameters, suggesting that it may have value as an indicator of prognosis. In this review, we bring together this growing literature on NRG-1 and its significance in cardiovascular development and disease. PMID:23104879

A Real-Time Rejection Circuit to Automatically Reject Multiple Interfering Hopping Signals While Passing a Lower Level Desired Signal.

DTIC Science & Technology

contain the low level desired frequency components that are passed through an inverse transform device for producing a frequency domain signal of the desired signal uncorrupted by unwanted signals. Patent applications. (RRH)

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.

The influence of smoking on radiation-induced bystander signal production in esophageal cancer patients.

PubMed

Hanu, C; Timotin, E; Wong, R; Sur, R K; Hayward, J E; Seymour, C B; Mothersill, C E

2016-05-01

The relevance of radiation-induced bystander effects in humans is unclear. Much of the existing data relate to cell lines but the effect of bystander signals in complex human tissues is unclear. A phase II clinical study was untaken, where blood sera from 60 patients along with 15 cancer-free volunteers were used to detect whether measurable bystander factor(s) could be found in the blood following high dose rate (HDR) brachytherapy. Overall, there was no significant change in bystander signal production (measured in a human keratinocyte reporter system) before and after one treatment fraction of HDR brachytherapy (p>0.05). Further assessment of patient characteristics and environmental modifiable factors including smoking were also analyzed. Similar to previously published data, samples taken from smokers produced weaker signals compared to non-smokers (p<0.05). Although the number of non-smoking subjects was low, there was a clear decrease in cloning efficiency observed in keratinocyte cultures for these patients that requires further study. This study found that samples taken from smokers do not produce bystander signals, whereas samples taken from non-smokers can produce such signals following HDR brachytherapy. These findings highlight the importance of studying the interactions of multiple stressors including environmental modifiers with radiation, since some factors such as smoking may elicit protection in tumor cells which could counteract the effectiveness of radiation therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

The role of ROS signaling in cross-tolerance: from model to crop

PubMed Central

Perez, Ilse Barrios; Brown, Patrick J.

2014-01-01

Reactive oxygen species (ROS) are key signaling molecules produced in response to biotic and abiotic stresses that trigger a variety of plant defense responses. Cross-tolerance, the enhanced ability of a plant to tolerate multiple stresses, has been suggested to result partly from overlap between ROS signaling mechanisms. Cross-tolerance can manifest itself both as a positive genetic correlation between tolerance to different stresses (inherent cross-tolerance), and as the priming of systemic plant tolerance through previous exposure to another type of stress (induced cross-tolerance). Research in model organisms suggests that cross-tolerance could be used to benefit the agronomy and breeding of crop plants. However, research under field conditions has been scarce and critical issues including the timing, duration, and intensity of a stressor, as well as its interactions with other biotic and abiotic factors, remain to be addressed. Potential applications include the use of chemical stressors to screen for stress-resistant genotypes in breeding programs and the agronomic use of chemical inducers of plant defense for plant protection. Success of these applications will rely on improving our understanding of how ROS signals travel systemically and persist over time, and of how genetic correlations between resistance to ROS, biotic, and abiotic stresses are shaped by cooperative and antagonistic interactions within the underlying signaling pathways. PMID:25566313

The postsynaptic t-SNARE Syntaxin 4 controls traffic of Neuroligin 1 and Synaptotagmin 4 to regulate retrograde signaling.

PubMed

Harris, Kathryn P; Zhang, Yao V; Piccioli, Zachary D; Perrimon, Norbert; Littleton, J Troy

2016-05-25

Postsynaptic cells can induce synaptic plasticity through the release of activity-dependent retrograde signals. We previously described a Ca(2+)-dependent retrograde signaling pathway mediated by postsynaptic Synaptotagmin 4 (Syt4). To identify proteins involved in postsynaptic exocytosis, we conducted a screen for candidates that disrupted trafficking of a pHluorin-tagged Syt4 at Drosophila neuromuscular junctions (NMJs). Here we characterize one candidate, the postsynaptic t-SNARE Syntaxin 4 (Syx4). Analysis of Syx4 mutants reveals that Syx4 mediates retrograde signaling, modulating the membrane levels of Syt4 and the transsynaptic adhesion protein Neuroligin 1 (Nlg1). Syx4-dependent trafficking regulates synaptic development, including controlling synaptic bouton number and the ability to bud new varicosities in response to acute neuronal stimulation. Genetic interaction experiments demonstrate Syx4, Syt4, and Nlg1 regulate synaptic growth and plasticity through both shared and parallel signaling pathways. Our findings suggest a conserved postsynaptic SNARE machinery controls multiple aspects of retrograde signaling and cargo trafficking within the postsynaptic compartment.

Targeting Insulin Signaling for the Treatment of Alzheimer's Disease.

PubMed

Chen, Yanxing; Zhang, Jianfang; Zhang, Baorong; Gong, Cheng-Xin

2016-01-01

Sporadic Alzheimer's disease (AD) is caused by multiple etiological factors, among which impaired brain insulin signaling and decreased brain glucose metabolism are important metabolic factors. Contrary to previous belief that insulin would not act in the brain, studies in the last three decades have proven important roles of insulin and insulin signaling in various biological functions in the brain. Impaired brain insulin signaling or brain insulin resistance and its role in the molecular pathogenesis of sporadic AD have been demonstrated. Thus, targeting brain insulin signaling for the treatment of cognitive impairment and AD has now attracted much attention in the field of AD drug discovery. This article reviews recent studies that target brain insulin signaling, especially those investigations on intranasal insulin administration and drugs that improve insulin sensitivity, including incretins, dipeptidyl peptidase IV inhibitors, thiazolidinediones, and metformin. These drugs have been previously approved for the treatment of diabetes mellitus, which could expedite their development for the treatment of AD. Although larger clinical trials are needed for validating their efficacy for the treatment of cognitive impairment and AD, results of animal studies and clinical trials available to date are encouraging.

Detection and signal amplification in zebrafish RNA FISH.

PubMed

Hauptmann, Giselbert; Lauter, Gilbert; Söll, Iris

2016-04-01

In situ hybridization (ISH) has become an invaluable tool for the detection of RNA in cells, tissues and organisms. Due to improvements in target and signal amplification and in probe design remarkable progress has been made concerning sensitivity, specificity and resolution of chromogenic and fluorescent ISH (FISH). These advancements allow for exquisite cellular and sub-cellular resolution and for detecting multiple RNA species at a time by multiplexing. In zebrafish (F)ISH non-enzymatic and enzymatic amplification systems have been employed to obtain enhanced signal intensities and signal-to-noise ratios. These amplification strategies include branched DNA-based RNAscope and in situ hybridization chain reaction (HCR) techniques, as well as alkaline phosphatase (AP)- and horseradish peroxidase (PO)-based immunoassays. For practical application, we provide proven multiplex FISH protocols for AP- and PO-based visualization of mRNAs at high resolution. The protocols take advantage of optimized tyramide signal amplification (TSA) conditions of the PO assay and long-lasting high signal-to-noise ratio of the AP reaction, thereby enabling detection of less abundant transcripts. Copyright © 2016 Elsevier Inc. All rights reserved.

Development of the Average Likelihood Function for Code Division Multiple Access (CDMA) Using BPSK and QPSK Symbols

DTIC Science & Technology

2015-01-01

This research has the purpose to establish a foundation for new classification and estimation of CDMA signals. Keywords: DS / CDMA signals, BPSK, QPSK...DEVELOPMENT OF THE AVERAGE LIKELIHOOD FUNCTION FOR CODE DIVISION MULTIPLE ACCESS ( CDMA ) USING BPSK AND QPSK SYMBOLS JANUARY 2015...To) OCT 2013 – OCT 2014 4. TITLE AND SUBTITLE DEVELOPMENT OF THE AVERAGE LIKELIHOOD FUNCTION FOR CODE DIVISION MULTIPLE ACCESS ( CDMA ) USING BPSK

Field Crickets Compensate for Unattractive Static Long-Distance Call Components by Increasing Dynamic Signalling Effort

PubMed Central

McAuley, Emily M.

2016-01-01

The evolution of multiple sexual signals presents a dilemma since individuals selecting a mate should pay attention to the most honest signal and ignore the rest; however, multiple signals may evolve if, together, they provide more information to the receiver than either one would alone. Static and dynamic signals, for instance, can act as multiple messages, providing information on different aspects of signaller quality that reflect condition at different time scales. While the nature of static signals makes them difficult or impossible for individuals to augment, dynamic signals are much more susceptible to temporary fluctuations in effort. We investigated whether male Texas field crickets, Gryllus texensis, that produce unattractive static signals compensate by dynamically increasing their calling effort. Our findings lend partial support to the compensation hypothesis, as males that called at unattractive carrier frequencies (a static trait) spent more time calling each night (a dynamic trait). Interestingly, this finding was most pronounced in males that called with attractive pulse characteristics (static traits) but did not occur in males that called with unattractive pulse characteristics. Males that signalled with unattractive pulse characteristics (duration and pause) spent less time calling through the night. Our correlative findings on wild caught males suggest that only males that signal with attractive pulse characteristics may be able to afford to pay the costs of both trait exaggeration and increased calling effort to compensate for poor carrier frequencies. PMID:27936045

Optimization of magnetic flux density measurement using multiple RF receiver coils and multi-echo in MREIT.

PubMed

Jeong, Woo Chul; Chauhan, Munish; Sajib, Saurav Z K; Kim, Hyung Joong; Serša, Igor; Kwon, Oh In; Woo, Eung Je

2014-09-07

Magnetic Resonance Electrical Impedance Tomography (MREIT) is an MRI method that enables mapping of internal conductivity and/or current density via measurements of magnetic flux density signals. The MREIT measures only the z-component of the induced magnetic flux density B = (Bx, By, Bz) by external current injection. The measured noise of Bz complicates recovery of magnetic flux density maps, resulting in lower quality conductivity and current-density maps. We present a new method for more accurate measurement of the spatial gradient of the magnetic flux density gradient (∇ Bz). The method relies on the use of multiple radio-frequency receiver coils and an interleaved multi-echo pulse sequence that acquires multiple sampling points within each repetition time. The noise level of the measured magnetic flux density Bz depends on the decay rate of the signal magnitude, the injection current duration, and the coil sensitivity map. The proposed method uses three key steps. The first step is to determine a representative magnetic flux density gradient from multiple receiver coils by using a weighted combination and by denoising the measured noisy data. The second step is to optimize the magnetic flux density gradient by using multi-echo magnetic flux densities at each pixel in order to reduce the noise level of ∇ Bz and the third step is to remove a random noise component from the recovered ∇ Bz by solving an elliptic partial differential equation in a region of interest. Numerical simulation experiments using a cylindrical phantom model with included regions of low MRI signal to noise ('defects') verified the proposed method. Experimental results using a real phantom experiment, that included three different kinds of anomalies, demonstrated that the proposed method reduced the noise level of the measured magnetic flux density. The quality of the recovered conductivity maps using denoised ∇ Bz data showed that the proposed method reduced the conductivity noise level up to 3-4 times at each anomaly region in comparison to the conventional method.

The evolution of neuropeptide signalling: insights from echinoderms.

PubMed

Semmens, Dean C; Elphick, Maurice R

2017-09-01

Neuropeptides are evolutionarily ancient mediators of neuronal signalling that regulate a wide range of physiological processes and behaviours in animals. Neuropeptide signalling has been investigated extensively in vertebrates and protostomian invertebrates, which include the ecdysozoans Drosophila melanogaster (Phylum Arthropoda) and Caenorhabditis elegans (Phylum Nematoda). However, until recently, an understanding of evolutionary relationships between neuropeptide signalling systems in vertebrates and protostomes has been impaired by a lack of genome/transcriptome sequence data from non-ecdysozoan invertebrates. The echinoderms-a deuterostomian phylum that includes sea urchins, sea cucumbers and starfish-have been particularly important in providing new insights into neuropeptide evolution. Sequencing of the genome of the sea urchin Strongylocentrotus purpuratus (Class Echinoidea) enabled discovery of (i) the first invertebrate thyrotropin-releasing hormone-type precursor, (ii) the first deuterostomian pedal peptide/orcokinin-type precursors and (iii) NG peptides-the 'missing link' between neuropeptide S in tetrapod vertebrates and crustacean cardioactive peptide in protostomes. More recently, sequencing of the neural transcriptome of the starfish Asterias rubens (Class Asteroidea) enabled identification of 40 neuropeptide precursors, including the first kisspeptin and melanin-concentrating hormone-type precursors to be identified outside of the chordates. Furthermore, the characterization of a corazonin-type neuropeptide signalling system in A. rubens has provided important new insights into the evolution of gonadotropin-releasing hormone-related neuropeptides. Looking forward, the discovery of multiple neuropeptide signalling systems in echinoderms provides opportunities to investigate how these systems are used to regulate physiological and behavioural processes in the unique context of a decentralized, pentaradial bauplan. © The Author 2017. Published by Oxford University Press.

Time-reversal MUSIC imaging of extended targets.

PubMed

Marengo, Edwin A; Gruber, Fred K; Simonetti, Francesco

2007-08-01

This paper develops, within a general framework that is applicable to rather arbitrary electromagnetic and acoustic remote sensing systems, a theory of time-reversal "MUltiple Signal Classification" (MUSIC)-based imaging of extended (nonpoint-like) scatterers (targets). The general analysis applies to arbitrary remote sensing geometry and sheds light onto how the singular system of the scattering matrix relates to the geometrical and propagation characteristics of the entire transmitter-target-receiver system and how to use this effect for imaging. All the developments are derived within exact scattering theory which includes multiple scattering effects. The derived time-reversal MUSIC methods include both interior sampling, as well as exterior sampling (or enclosure) approaches. For presentation simplicity, particular attention is given to the time-harmonic case where the informational wave modes employed for target interrogation are purely spatial, but the corresponding generalization to broadband fields is also given. This paper includes computer simulations illustrating the derived theory and algorithms.

Waveform-Diverse Multiple-Input Multiple-Output Radar Imaging Measurements

NASA Astrophysics Data System (ADS)

Stewart, Kyle B.

Multiple-input multiple-output (MIMO) radar is an emerging set of technologies designed to extend the capabilities of multi-channel radar systems. While conventional radar architectures emphasize the use of antenna array beamforming to maximize real-time power on target, MIMO radar systems instead attempt to preserve some degree of independence between their received signals and to exploit this expanded matrix of target measurements in the signal-processing domain. Specifically the use of sparse “virtual” antenna arrays may allow MIMO radars to achieve gains over traditional multi-channel systems by post-processing diverse received signals to implement both transmit and receive beamforming at all points of interest within a given scene. MIMO architectures have been widely examined for use in radar target detection, but these systems may yet be ideally suited to real and synthetic aperture radar imaging applications where their proposed benefits include improved resolutions, expanded area coverage, novel modes of operation, and a reduction in hardware size, weight, and cost. While MIMO radar's theoretical benefits have been well established in the literature, its practical limitations have not received great attention thus far. The effective use of MIMO radar techniques requires a diversity of signals, and to date almost all MIMO system demonstrations have made use of time-staggered transmission to satisfy this requirement. Doing so is reliable but can be prohibitively slow. Waveform-diverse systems have been proposed as an alternative in which multiple, independent waveforms are broadcast simultaneously over a common bandwidth and separated on receive using signal processing. Operating in this way is much faster than its time-diverse equivalent, but finding a set of suitable waveforms for this technique has proven to be a difficult problem. In light of this, many have questioned the practicality of MIMO radar imaging and whether or not its theoretical benefits may be extended to real systems. Work in this writing focuses specifically on the practical aspects of MIMO radar imaging systems and provides performance data sourced from experimental measurements made using a four-channel software-defined MIMO radar platform. Demonstrations of waveform-diverse imaging data products are provided and compared directly against time-diverse equivalents in order to assess the performance of prospective MIMO waveforms. These are sourced from the pseudo-noise, short-term shift orthogonal, and orthogonal frequency multiplexing signal families while experimental results demonstrate waveform-diverse measurements of polarimetric radar cross section, top-down stationary target images, and finally volumetric MIMO synthetic aperture radar imagery. The data presented represents some of the first available concerning the overall practicality of waveform-diverse MIMO radar architectures, and results suggest that such configurations may achieve a reasonable degree of performance even in the presence of significant practical limitations.

Simultaneous estimation of multiple phases in digital holographic interferometry using state space analysis

NASA Astrophysics Data System (ADS)

Kulkarni, Rishikesh; Rastogi, Pramod

2018-05-01

A new approach is proposed for the multiple phase estimation from a multicomponent exponential phase signal recorded in multi-beam digital holographic interferometry. It is capable of providing multidimensional measurements in a simultaneous manner from a single recording of the exponential phase signal encoding multiple phases. Each phase within a small window around each pixel is appproximated with a first order polynomial function of spatial coordinates. The problem of accurate estimation of polynomial coefficients, and in turn the unwrapped phases, is formulated as a state space analysis wherein the coefficients and signal amplitudes are set as the elements of a state vector. The state estimation is performed using the extended Kalman filter. An amplitude discrimination criterion is utilized in order to unambiguously estimate the coefficients associated with the individual signal components. The performance of proposed method is stable over a wide range of the ratio of signal amplitudes. The pixelwise phase estimation approach of the proposed method allows it to handle the fringe patterns that may contain invalid regions.

KLF4, p21 and context-dependent opposing forces in cancer.

PubMed

Rowland, Benjamin D; Peeper, Daniel S

2006-01-01

Krüppel-like factors are transcriptional regulators that influence several cellular functions, including proliferation. Recent studies have shown that one family member, KLF4, can function both as a tumour suppressor and an oncogene. The ability of KLF4 to affect the levels of expression of the cell-cycle regulator p21 seems to be involved, in that this protein might function as a switch that determines the outcome of KLF4 signalling. Is this role of p21 restricted to KLF4, or does p21 represent a nodal point for signals from multiple other factors with opposing functions in cancer?

High Precision Laser Range Sensor

NASA Technical Reports Server (NTRS)

Dubovitsky, Serge (Inventor); Lay, Oliver P. (Inventor)

2003-01-01

The present invention is an improved distance measuring interferometer that includes high speed phase modulators and additional phase meters to generate and analyze multiple heterodyne signal pairs with distinct frequencies. Modulation sidebands with large frequency separation are generated by the high speed electro-optic phase modulators, requiring only a single frequency stable laser source and eliminating the need for a fist laser to be tuned or stabilized relative to a second laser. The combination of signals produced by the modulated sidebands is separated and processed to give the target distance. The resulting metrology apparatus enables a sensor with submicron accuracy or better over a multi- kilometer ambiguity range.

Caspases and Kinases in a Death Grip

PubMed Central

Kurokawa, Manabu; Kornbluth, Sally

2011-01-01

The complex process of apoptosis is orchestrated by caspases, a family of cysteine proteases with unique substrate specificities. Accumulating evidence suggests that cell death pathways are finely tuned by multiple signaling events, including direct phosphorylation of caspases, whereas kinases are often substrates of active caspases. Importantly, caspase-mediated cleavage of kinases can terminate prosurvival signaling or generate proapoptotic peptide fragments that help to execute the death program and facilitate packaging of the dying cells. Here, we review caspases as kinase substrates and kinases as caspase substrates and discuss how the balance between cell survival and cell death can be shifted through crosstalk between these two enzyme families. PMID:19737514

Pulse transmission receiver with higher-order time derivative pulse generator

DOEpatents

Dress, Jr., William B.; Smith, Stephen F.

2003-08-12

Systems and methods for pulse-transmission low-power communication modes are disclosed. A pulse transmission receiver includes: a front-end amplification/processing circuit; a synchronization circuit coupled to the front-end amplification/processing circuit; a clock coupled to the synchronization circuit; a trigger signal generator coupled to the clock; and at least one higher-order time derivative pulse generator coupled to the trigger signal generator. The systems and methods significantly reduce lower-frequency emissions from pulse transmission spread-spectrum communication modes, which reduces potentially harmful interference to existing radio frequency services and users and also simultaneously permit transmission of multiple data bits by utilizing specific pulse shapes.

Yes-associated protein (YAP) in pancreatic cancer: at the epicenter of a targetable signaling network associated with patient survival.

PubMed

Rozengurt, Enrique; Sinnett-Smith, James; Eibl, Guido

2018-01-01

Pancreatic ductal adenocarcinoma (PDAC) is generally a fatal disease with no efficacious treatment modalities. Elucidation of signaling mechanisms that will lead to the identification of novel targets for therapy and chemoprevention is urgently needed. Here, we review the role of Yes-associated protein (YAP) and WW-domain-containing Transcriptional co-Activator with a PDZ-binding motif (TAZ) in the development of PDAC. These oncogenic proteins are at the center of a signaling network that involves multiple upstream signals and downstream YAP-regulated genes. We also discuss the clinical significance of the YAP signaling network in PDAC using a recently published interactive open-access database (www.proteinatlas.org/pathology) that allows genome-wide exploration of the impact of individual proteins on survival outcomes. Multiple YAP/TEAD-regulated genes, including AJUBA , ANLN , AREG , ARHGAP29 , AURKA , BUB1 , CCND1 , CDK6, CXCL5 , EDN2 , DKK1 , FOSL1,FOXM1 , HBEGF , IGFBP2 , JAG1 , NOTCH2 , RHAMM , RRM2 , SERP1 , and ZWILCH , are associated with unfavorable survival of PDAC patients. Similarly, components of AP-1 that synergize with YAP ( FOSL1 ), growth factors (TGFα, EPEG, and HBEGF), a specific integrin ( ITGA2 ), heptahelical receptors ( P2Y 2 R , GPR87 ) and an inhibitor of the Hippo pathway ( MUC1 ), all of which stimulate YAP activity, are associated with unfavorable survival of PDAC patients. By contrast, YAP inhibitory pathways (STRAD/LKB-1/AMPK, PKA/LATS, and TSC/mTORC1) indicate a favorable prognosis. These associations emphasize that the YAP signaling network correlates with poor survival of pancreatic cancer patients. We conclude that the YAP pathway is a major determinant of clinical aggressiveness in PDAC patients and a target for therapeutic and preventive strategies in this disease.

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

Insights into Rapid Modulation of Neuroplasticity by Brain Estrogens

PubMed Central

Woolfrey, Kevin M.; Penzes, Peter

2013-01-01

Converging evidence from cellular, electrophysiological, anatomic, and behavioral studies suggests that the remodeling of synapse structure and function is a critical component of cognition. This modulation of neuroplasticity can be achieved through the actions of numerous extracellular signals. Moreover, it is thought that it is the integration of different extracellular signals regulation of neuroplasticity that greatly influences cognitive function. One group of signals that exerts powerful effects on multiple neurologic processes is estrogens. Classically, estrogens have been described to exert their effects over a period of hours to days. However, there is now increasing evidence that estrogens can rapidly influence multiple behaviors, including those that require forebrain neural circuitry. Moreover, these effects are found in both sexes. Critically, it is now emerging that the modulation of cognition by rapid estrogenic signaling is achieved by activation of specific signaling cascades and regulation of synapse structure and function, cumulating in the rewiring of neural circuits. The importance of understanding the rapid effects of estrogens on forebrain function and circuitry is further emphasized as investigations continue to consider the potential of estrogenic-based therapies for neuropathologies. This review focuses on how estrogens can rapidly influence cognition and the emerging mechanisms that underlie these effects. We discuss the potential sources and the biosynthesis of estrogens within the brain and the consequences of rapid estrogenic-signaling on the remodeling of neural circuits. Furthermore, we argue that estrogens act via distinct signaling pathways to modulate synapse structure and function in a manner that may vary with cell type, developmental stage, and sex. Finally, we present a model in which the coordination of rapid estrogenic-signaling and activity-dependent stimuli can result in long-lasting changes in neural circuits, contributing to cognition, with potential relevance for the development of novel estrogenic-based therapies for neurodevelopmental or neurodegenerative disorders. PMID:24076546

Laplace Transform Based Radiative Transfer Studies

NASA Astrophysics Data System (ADS)

Hu, Y.; Lin, B.; Ng, T.; Yang, P.; Wiscombe, W.; Herath, J.; Duffy, D.

2006-12-01

Multiple scattering is the major uncertainty for data analysis of space-based lidar measurements. Until now, accurate quantitative lidar data analysis has been limited to very thin objects that are dominated by single scattering, where photons from the laser beam only scatter a single time with particles in the atmosphere before reaching the receiver, and simple linear relationship between physical property and lidar signal exists. In reality, multiple scattering is always a factor in space-based lidar measurement and it dominates space- based lidar returns from clouds, dust aerosols, vegetation canopy and phytoplankton. While multiple scattering are clear signals, the lack of a fast-enough lidar multiple scattering computation tool forces us to treat the signal as unwanted "noise" and use simple multiple scattering correction scheme to remove them. Such multiple scattering treatments waste the multiple scattering signals and may cause orders of magnitude errors in retrieved physical properties. Thus the lack of fast and accurate time-dependent radiative transfer tools significantly limits lidar remote sensing capabilities. Analyzing lidar multiple scattering signals requires fast and accurate time-dependent radiative transfer computations. Currently, multiple scattering is done with Monte Carlo simulations. Monte Carlo simulations take minutes to hours and are too slow for interactive satellite data analysis processes and can only be used to help system / algorithm design and error assessment. We present an innovative physics approach to solve the time-dependent radiative transfer problem. The technique utilizes FPGA based reconfigurable computing hardware. The approach is as following, 1. Physics solution: Perform Laplace transform on the time and spatial dimensions and Fourier transform on the viewing azimuth dimension, and convert the radiative transfer differential equation solving into a fast matrix inversion problem. The majority of the radiative transfer computation goes to matrix inversion processes, FFT and inverse Laplace transforms. 2. Hardware solutions: Perform the well-defined matrix inversion, FFT and Laplace transforms on highly parallel, reconfigurable computing hardware. This physics-based computational tool leads to accurate quantitative analysis of space-based lidar signals and improves data quality of current lidar mission such as CALIPSO. This presentation will introduce the basic idea of this approach, preliminary results based on SRC's FPGA-based Mapstation, and how we may apply it to CALIPSO data analysis.

Targeting agr- and agr-Like Quorum Sensing Systems for Development of Common Therapeutics to Treat Multiple Gram-Positive Bacterial Infections

PubMed Central

Gray, Brian; Hall, Pamela; Gresham, Hattie

2013-01-01

Invasive infection by the Gram-positive pathogen Staphylococcus aureus is controlled by a four gene operon, agr that encodes a quorum sensing system for the regulation of virulence. While agr has been well studied in S. aureus, the contribution of agr homologues and analogues in other Gram-positive pathogens is just beginning to be understood. Intriguingly, other significant human pathogens, including Clostridium perfringens, Listeria monocytogenes, and Enterococcus faecalis contain agr or analogues linked to virulence. Moreover, other significant human Gram-positive pathogens use peptide based quorum sensing systems to establish or maintain infection. The potential for commonality in aspects of these signaling systems across different species raises the prospect of identifying therapeutics that could target multiple pathogens. Here, we review the status of research into these agr homologues, analogues, and other peptide based quorum sensing systems in Gram-positive pathogens as well as the potential for identifying common pathways and signaling mechanisms for therapeutic discovery. PMID:23598501

The Cryptococcus neoformans Capsule: a Sword and a Shield

PubMed Central

O'Meara, Teresa R.

2012-01-01

Summary: The human fungal pathogen Cryptococcus neoformans is characterized by its ability to induce a distinct polysaccharide capsule in response to a number of host-specific environmental stimuli. The induction of capsule is a complex biological process encompassing regulation at multiple steps, including the biosynthesis, transport, and maintenance of the polysaccharide at the cell surface. By precisely regulating the composition of its cell surface and secreted polysaccharides, C. neoformans has developed intricate ways to establish chronic infection and dormancy in the human host. The plasticity of the capsule structure in response to various host conditions also underscores the complex relationship between host and parasite. Much of this precise regulation of capsule is achieved through the transcriptional responses of multiple conserved signaling pathways that have been coopted to regulate this C. neoformans-specific virulence-associated phenotype. This review focuses on specific host stimuli that trigger the activation of the signal transduction cascades and on the downstream transcriptional responses that are required for robust encapsulation around the cell. PMID:22763631

Retrieval of Droplet size Density Distribution from Multiple field of view Cross polarized Lidar Signals: Theory and Experimental Validation

DTIC Science & Technology

2016-06-02

Retrieval of droplet-size density distribution from multiple-field-of-view cross-polarized lidar signals: theory and experimental validation...theoretical and experimental studies of mul- tiple scattering and multiple-field-of-view (MFOV) li- dar detection have made possible the retrieval of cloud...droplet cloud are typical of Rayleigh scattering, with a signature close to a dipole (phase function quasi -flat and a zero-depolarization ratio

On using the Multiple Signal Classification algorithm to study microbaroms

NASA Astrophysics Data System (ADS)

Marcillo, O. E.; Blom, P. S.; Euler, G. G.

2016-12-01

Multiple Signal Classification (MUSIC) (Schmidt, 1986) is a well-known high-resolution algorithm used in array processing for parameter estimation. We report on the application of MUSIC to infrasonic array data in a study of the structure of microbaroms. Microbaroms can be globally observed and display energy centered around 0.2 Hz. Microbaroms are an infrasonic signal generated by the non-linear interaction of ocean surface waves that radiate into the ocean and atmosphere as well as the solid earth in the form of microseisms. Microbaroms sources are dynamic and, in many cases, distributed in space and moving in time. We assume that the microbarom energy detected by an infrasonic array is the result of multiple sources (with different back-azimuths) in the same bandwidth and apply the MUSIC algorithm accordingly to recover the back-azimuth and trace velocity of the individual components. Preliminary results show that the multiple component assumption in MUSIC allows one to resolve the fine structure in the microbarom band that can be related to multiple ocean surface phenomena.

Epithelial-mesenchymal transition is associated with a distinct tumor microenvironment including elevation of inflammatory signals and multiple immune checkpoints in lung adenocarcinoma

PubMed Central

Lou, Yanyan; Diao, Lixia; Cuentas, Edwin Roger Parra; Denning, Warren L.; Chen, Limo; Fan, Youhong; Byers, Lauren A.; Wang, Jing; Papadimitrakopoulou, Vassiliki; Behrens, Carmen; Rodriguez, Jaime Canales; Hwu, Patrick; Wistuba, Ignacio I.; Heymach, John V.; Gibbons, Don L.

2016-01-01

Purpose Promising results in the treatment of NSCLC have been seen with agents targeting immune checkpoints, such as PD-1 or PD-L1. However, only a select group of patients respond to these interventions. The identification of biomarkers that predict clinical benefit to immune checkpoint blockade is critical to successful clinical translation of these agents. Methods We conducted an integrated analysis of three independent large datasets, including The Cancer Genome Atlas (TCGA) of lung adenocarcinoma and two datasets from MD Anderson Cancer Center, Profiling of Resistance patterns and Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax (named PROSPECT) and Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (named BATTLE-1). Comprehensive analysis of mRNA gene expression, reverse phase protein array (RPPA), immunohistochemistry and correlation with clinical data were performed. Results Epithelial-mesenchymal transition (EMT) is highly associated with an inflammatory tumor microenvironment in lung adenocarcinoma, independent of tumor mutational burden. We found immune activation co-existent with elevation of multiple targetable immune checkpoint molecules, including PD-L1, PD-L2, PD-1, TIM-3, B7-H3, BTLA and CTLA-4, along with increases in tumor infiltration by CD4+Foxp3+ regulatory T cells in lung adenocarcinomas that displayed an EMT phenotype. Furthermore, we identify B7-H3 as a prognostic marker for NSCLC. Conclusions The strong association between EMT status and an inflammatory tumor microenvironment with elevation of multiple targetable immune checkpoint molecules warrants further investigation of using EMT as a predictive biomarker for immune checkpoint blockade agents and other immunotherapies in NSCLC and possibly a broad range of other cancers. PMID:26851185

Multi-frequency EIT system with radially symmetric architecture: KHU Mark1.

PubMed

Oh, Tong In; Woo, Eung Je; Holder, David

2007-07-01

We describe the development of a multi-frequency electrical impedance tomography (EIT) system (KHU Mark1) with a single balanced current source and multiple voltmeters. It was primarily designed for imaging brain function with a flexible strategy for addressing electrodes and a frequency range from 10 Hz-500 kHz. The maximal number of voltmeters is 64, and all of them can simultaneously acquire and demodulate voltage signals. Each voltmeter measures a differential voltage between a pair of electrodes. All voltmeters are configured in a radially symmetric architecture in order to optimize the routing of wires and minimize cross-talk. We adopted several techniques from existing EIT systems including digital waveform generation, a Howland current generator with a generalized impedance converter (GIC), digital phase-sensitive demodulation and tri-axial cables. New features of the KHU Mark1 system include multiple GIC circuits to maximize the output impedance of the current source at multiple frequencies. The voltmeter employs contact impedance measurements, data overflow detection, spike noise rejection, automatic gain control and programmable data averaging. The KHU Mark1 system measures both in-phase and quadrature components of trans-impedances. By using a script file describing an operating mode, the system setup can be easily changed. The performance of the developed multi-frequency EIT system was evaluated in terms of a common-mode rejection ratio, signal-to-noise ratio, linearity error and reciprocity error. Time-difference and frequency-difference images of a saline phantom with a banana object are presented showing a frequency-dependent complex conductivity of the banana. Future design of a more innovative system is suggested including miniaturization and wireless techniques.

Load sensing system

DOEpatents

Sohns, Carl W.; Nodine, Robert N.; Wallace, Steven Allen

1999-01-01

A load sensing system inexpensively monitors the weight and temperature of stored nuclear material for long periods of time in widely variable environments. The system can include an electrostatic load cell that encodes weight and temperature into a digital signal which is sent to a remote monitor via a coaxial cable. The same cable is used to supply the load cell with power. When multiple load cells are used, vast

Interrelationship of canonical and non-canonical Wnt signalling pathways in chronic metabolic diseases.

PubMed

Ackers, Ian; Malgor, Ramiro

2018-01-01

Chronic diseases account for approximately 45% of all deaths in developed countries and are particularly prevalent in countries with the most sophisticated and robust public health systems. Chronic metabolic diseases, specifically lifestyle-related diseases pertaining to diet and exercise, continue to be difficult to treat clinically. The most prevalent of these chronic metabolic diseases include obesity, diabetes, non-alcoholic fatty liver disease, chronic kidney disease and cardiovascular disease and will be the focus of this review. Wnt proteins are highly conserved glycoproteins best known for their role in development and homeostasis of tissues. Given the importance of Wnt signalling in homeostasis, aberrant Wnt signalling likely regulates metabolic processes and may contribute to the development of chronic metabolic diseases. Expression of Wnt proteins and dysfunctional Wnt signalling has been reported in multiple chronic diseases. It is interesting to speculate about an interrelationship between the Wnt signalling pathways as a potential pathological mechanism in chronic metabolic diseases. The aim of this review is to summarize reported findings on the contrasting roles of Wnt signalling in lifestyle-related chronic metabolic diseases; specifically, the contribution of Wnt signalling to lipid accumulation, fibrosis and chronic low-grade inflammation.

Signal propagation and logic gating in networks of integrate-and-fire neurons.

PubMed

Vogels, Tim P; Abbott, L F

2005-11-16

Transmission of signals within the brain is essential for cognitive function, but it is not clear how neural circuits support reliable and accurate signal propagation over a sufficiently large dynamic range. Two modes of propagation have been studied: synfire chains, in which synchronous activity travels through feedforward layers of a neuronal network, and the propagation of fluctuations in firing rate across these layers. In both cases, a sufficient amount of noise, which was added to previous models from an external source, had to be included to support stable propagation. Sparse, randomly connected networks of spiking model neurons can generate chaotic patterns of activity. We investigate whether this activity, which is a more realistic noise source, is sufficient to allow for signal transmission. We find that, for rate-coded signals but not for synfire chains, such networks support robust and accurate signal reproduction through up to six layers if appropriate adjustments are made in synaptic strengths. We investigate the factors affecting transmission and show that multiple signals can propagate simultaneously along different pathways. Using this feature, we show how different types of logic gates can arise within the architecture of the random network through the strengthening of specific synapses.

ROS signaling and stomatal movement in plant responses to drought stress and pathogen attack.

PubMed

Qi, Junsheng; Song, Chun-Peng; Wang, Baoshan; Zhou, Jianmin; Kangasjärvi, Jaakko; Zhu, Jian-Kang; Gong, Zhizhong

2018-04-16

Stomata, the pores formed by a pair of guard cells, are the main gateways for water transpiration and photosynthetic CO 2 exchange, as well as pathogen invasion in land plants. Guard cell movement is regulated by a combination of environmental factors including water status, light, CO 2 levels and pathogen attack, as well as endogenous signals such as abscisic acid and apoplastic reactive oxygen species (ROS). Under abiotic and biotic stress conditions, extracellular ROS are mainly produced by plasma membrane-localized NADPH oxidases, whereas intracellular ROS are produced in multiple organelles. These ROS form a sophisticated cellular signaling network, with the accumulation of apoplastic ROS an early hallmark of stomatal movement. Here, we review recent progress in understanding the molecular mechanisms of the ROS signaling network, primarily during drought stress and pathogen attack. We summarize the roles of apoplastic ROS in regulating stomatal movement, ABA and CO 2 signaling, and immunity responses. Finally, we discuss ROS accumulation and communication between organelles and cells. This information provides a conceptual framework for understanding how ROS signaling is integrated with various signaling pathways during plant responses to abiotic and biotic stress stimuli. This article is protected by copyright. All rights reserved.

Interaction of Herbal Compounds with Biological Targets: A Case Study with Berberine

PubMed Central

Chen, Xiao-Wu; Di, Yuan Ming; Zhang, Jian; Zhou, Zhi-Wei; Li, Chun Guang; Zhou, Shu-Feng

2012-01-01

Berberine is one of the main alkaloids found in the Chinese herb Huang lian (Rhizoma Coptidis), which has been reported to have multiple pharmacological activities. This study aimed to analyze the molecular targets of berberine based on literature data followed by a pathway analysis using the PANTHER program. PANTHER analysis of berberine targets showed that the most classes of molecular functions include receptor binding, kinase activity, protein binding, transcription activity, DNA binding, and kinase regulator activity. Based on the biological process classification of in vitro berberine targets, those targets related to signal transduction, intracellular signalling cascade, cell surface receptor-linked signal transduction, cell motion, cell cycle control, immunity system process, and protein metabolic process are most frequently involved. In addition, berberine was found to interact with a mixture of biological pathways, such as Alzheimer's disease-presenilin and -secretase pathways, angiogenesis, apoptosis signalling pathway, FAS signalling pathway, Hungtington disease, inflammation mediated by chemokine and cytokine signalling pathways, interleukin signalling pathway, and p53 pathways. We also explored the possible mechanism of action for the anti-diabetic effect of berberine. Further studies are warranted to elucidate the mechanisms of action of berberine using systems biology approach. PMID:23213296

SLC12A7 alters adrenocortical carcinoma cell adhesion properties to promote an aggressive invasive behavior.

PubMed

Brown, Taylor C; Murtha, Timothy D; Rubinstein, Jill C; Korah, Reju; Carling, Tobias

2018-06-08

Altered expression of Solute Carrier Family 12 Member 7 (SLC12A7) is implicated to promote malignant behavior in multiple cancer types through an incompletely understood mechanism. Recent studies have shown recurrent gene amplifications and overexpression of SLC12A7 in adrenocortical carcinoma (ACC). The potential mechanistic effect(s) of SLC12A7 amplifications in portending an aggressive behavior in ACC has not been previously studied and is investigated here using two established ACC cell lines, SW-13 and NCI-H295R. SW-13 cells, which express negligible amounts of SLC12A7, were enforced to express SLC12A7 constitutively, while RNAi gene silencing was performed in NCI-H295R cells, which have robust endogenous expression of SLC12A7. In vitro studies tested the outcomes of experimental alterations in SLC12A7 expression on malignant characteristics, including cell viability, growth, colony formation potential, motility, invasive capacity, adhesion and detachment kinetics, and cell membrane organization. Further, potential alterations in transcription regulation downstream to induced SLC12A7 overexpression was explored using targeted transcription factor expression arrays. Enforced SLC12A7 overexpression in SW-13 cells robustly promoted motility and invasive characteristics (p < 0.05) without significantly altering cell viability, growth, or colony formation potential. SLC12A7 overexpression also significantly increased rates of cellular attachment and detachment turnover (p < 0.05), potentially propelled by increased filopodia formation and/or Ezrin interaction. In contrast, RNAi gene silencing of SLC12A7 stymied cell attachment strength as well as migration and invasion capacity in NCI-H295R cells. Transcription factor expression analysis identified multiple signally pathways potentially affected by SLC12A7 overexpression, including osmotic stress, bone morphogenetic protein, and Hippo signaling pathways. Amplification of SLC12A7 observed in ACCs is shown here, in vitro, to exacerbate the malignant behavior of ACC cells by promoting invasive capacities, possibly mediated by alterations in multiple signaling pathways, including the osmotic stress pathway.

Recording multiple spatially-heterodyned direct to digital holograms in one digital image

DOEpatents

Hanson, Gregory R [Clinton, TN; Bingham, Philip R [Knoxville, TN

2008-03-25

Systems and methods are described for recording multiple spatially-heterodyned direct to digital holograms in one digital image. A method includes digitally recording, at a first reference beam-object beam angle, a first spatially-heterodyned hologram including spatial heterodyne fringes for Fourier analysis; Fourier analyzing the recorded first spatially-heterodyned hologram by shifting a first original origin of the recorded first spatially-heterodyned hologram to sit on top of a first spatial-heterodyne carrier frequency defined by the first reference beam-object beam angle; digitally recording, at a second reference beam-object beam angle, a second spatially-heterodyned hologram including spatial heterodyne fringes for Fourier analysis; Fourier analyzing the recorded second spatially-heterodyned hologram by shifting a second original origin of the recorded second spatially-heterodyned hologram to sit on top of a second spatial-heterodyne carrier frequency defined by the second reference beam-object beam angle; applying a first digital filter to cut off signals around the first original origin and define a first result; performing a first inverse Fourier transform on the first result; applying a second digital filter to cut off signals around the second original origin and define a second result; and performing a second inverse Fourier transform on the second result, wherein the first reference beam-object beam angle is not equal to the second reference beam-object beam angle and a single digital image includes both the first spatially-heterodyned hologram and the second spatially-heterodyned hologram.

Everolimus improves neuropsychiatric symptoms in a patient with tuberous sclerosis carrying a novel TSC2 mutation.

PubMed

Hwang, Su-Kyeong; Lee, Jae-Hyung; Yang, Jung-Eun; Lim, Chae-Seok; Lee, Jin-A; Lee, Yong-Seok; Lee, Kyungmin; Kaang, Bong-Kiun

2016-05-23

Tuberous sclerosis complex (TSC) is a neurocutaneous disorder characterized by multiple symptoms including neuropsychological deficits such as seizures, intellectual disability, and autism. TSC is inherited in an autosomal dominant pattern and is caused by mutations in either the TSC1 or TSC2 genes, which enhance activation of the mammalian target of rapamycin (mTOR) signaling pathway. Recent studies have suggested that mTOR inhibitors such as rapamycin can reverse TSC-associated deficits in rodent models of TSC. In addition, clinical trials are ongoing to test the efficacy of mTOR inhibitors toward the psychiatric symptoms associated with TSC. Here, we report a case study of a Korean patient with TSC, who exhibited multiple symptoms including frequent seizures, intellectual disability, language delays, and social problems. We performed whole exome sequencing and identified a novel small deletion mutation in TSC2. Expressing the novel deletion mutant in HEK293T cells significantly increased mTOR pathway activation. Furthermore, everolimus treatment showed not only reduction in SEGA size, but dramatically improved behavioral deficits including autism related behaviors in the patient. In summary, we identified a novel small deletion mutation in TSC2 associated with severe TSC in a Korean family that enhances the activation of mTOR signaling in vitro. Everolimus treatment improved behavioral deficits in the patient.

Using Multiple Schedules during Functional Communication Training to Promote Rapid Transfer of Treatment Effects

ERIC Educational Resources Information Center

Fisher, Wayne W.; Greer, Brian D.; Fuhrman, Ashley M.; Querim, Angie C.

2015-01-01

Multiple schedules with signaled periods of reinforcement and extinction have been used to thin reinforcement schedules during functional communication training (FCT) to make the intervention more practical for parents and teachers. We evaluated whether these signals would also facilitate rapid transfer of treatment effects across settings and…

Comprehending Multiple Documents on Scientific Controversies: Effects of Reading Goals and Signaling Rhetorical Relationships

ERIC Educational Resources Information Center

Stadtler, Marc; Scharrer, Lisa; Skodzik, Timo; Bromme, Rainer

2014-01-01

Understanding conflicts between sources is an inherent part of science text comprehension. We examined whether readers' memories for conflicts and their situational interpretation of conflicts would be affected by reading goals and lexical cue phrases that signal rhetorical relationships. To this end, 198 undergraduates read multiple documents on…

Economical Implementation of a Filter Engine in an FPGA

NASA Technical Reports Server (NTRS)

Kowalski, James E.

2009-01-01

A logic design has been conceived for a field-programmable gate array (FPGA) that would implement a complex system of multiple digital state-space filters. The main innovative aspect of this design lies in providing for reuse of parts of the FPGA hardware to perform different parts of the filter computations at different times, in such a manner as to enable the timely performance of all required computations in the face of limitations on available FPGA hardware resources. The implementation of the digital state-space filter involves matrix vector multiplications, which, in the absence of the present innovation, would ordinarily necessitate some multiplexing of vector elements and/or routing of data flows along multiple paths. The design concept calls for implementing vector registers as shift registers to simplify operand access to multipliers and accumulators, obviating both multiplexing and routing of data along multiple paths. Each vector register would be reused for different parts of a calculation. Outputs would always be drawn from the same register, and inputs would always be loaded into the same register. A simple state machine would control each filter. The output of a given filter would be passed to the next filter, accompanied by a "valid" signal, which would start the state machine of the next filter. Multiple filter modules would share a multiplication/accumulation arithmetic unit. The filter computations would be timed by use of a clock having a frequency high enough, relative to the input and output data rate, to provide enough cycles for matrix and vector arithmetic operations. This design concept could prove beneficial in numerous applications in which digital filters are used and/or vectors are multiplied by coefficient matrices. Examples of such applications include general signal processing, filtering of signals in control systems, processing of geophysical measurements, and medical imaging. For these and other applications, it could be advantageous to combine compact FPGA digital filter implementations with other application-specific logic implementations on single integrated-circuit chips. An FPGA could readily be tailored to implement a variety of filters because the filter coefficients would be loaded into memory at startup.

Bruton’s Tyrosine Kinase, a Component of B Cell Signaling Pathways, Has Multiple Roles in the Pathogenesis of Lupus

PubMed Central

Satterthwaite, Anne B.

2018-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the loss of adaptive immune tolerance to nucleic acid-containing antigens. The resulting autoantibodies form immune complexes that promote inflammation and tissue damage. Defining the signals that drive pathogenic autoantibody production is an important step in the development of more targeted therapeutic approaches for lupus, which is currently treated primarily with non-specific immunosuppression. Here, we review the contribution of Bruton’s tyrosine kinase (Btk), a component of B and myeloid cell signaling pathways, to disease in murine lupus models. Both gain- and loss-of-function genetic studies have revealed that Btk plays multiple roles in the production of autoantibodies. These include promoting the activation, plasma cell differentiation, and class switching of autoreactive B cells. Small molecule inhibitors of Btk are effective at reducing autoantibody levels, B cell activation, and kidney damage in several lupus models. These studies suggest that Btk may promote end-organ damage both by facilitating the production of autoantibodies and by mediating the inflammatory response of myeloid cells to these immune complexes. While Btk has not been associated with SLE in GWAS studies, SLE B cells display signaling defects in components both upstream and downstream of Btk consistent with enhanced activation of Btk signaling pathways. Taken together, these observations indicate that limiting Btk activity is critical for maintaining B cell tolerance and preventing the development of autoimmune disease. Btk inhibitors, generally well-tolerated and approved to treat B cell malignancy, may thus be a useful therapeutic approach for SLE. PMID:29403475

GABA receptor subunit distribution and FMRP-mGluR5 signaling abnormalities in the cerebellum of subjects with schizophrenia, mood disorders, and autism

PubMed Central

Fatemi, S. Hossein; Folsom, Timothy D.

2016-01-01

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. GABAergic receptor abnormalities have been documented in several major psychiatric disorders including schizophrenia, mood disorders, and autism. Abnormal expression of mRNA and protein for multiple GABA receptors has also been observed in multiple brain regions leading to alterations in the balance between excitatory/inhibitory signaling in the brain with potential profound consequences for normal cognition and maintenance of mood and perception. Altered expression of GABAA receptor subunits has been documented in Fragile X mental retardation 1 (FMR1) knockout mice, suggesting that loss of its protein product, fragile X mental retardation protein (FMRP), impacts GABAA subunit expression. Recent postmortem studies from our laboratory have shown reduced expression of FMRP in brains of subjects with schizophrenia, bipolar disorder, major depression, and autism. FMRP acts as a translational repressor and, under normal conditions, inhibits metabotropic glutamate receptor 5 (mGluR5)-mediated signaling. In fragile X syndrome (FXS), absence of FMRP is hypothesized to lead to unregulated mGluR5 signaling, ultimately resulting in the behavioral and intellectual impairments associated with this disorder. Our laboratory has identified changes in mGluR5 expression in autism, schizophrenia, and mood disorders. In the current review article, we discuss our postmortem data on GABA receptors, FMRP, and mGluR5 levels and compare our results with other laboratories. Finally, we discuss the interactions between these molecules and the potential for new therapeutic interventions that target these interconnected signaling systems. PMID:25432637

Sparsity guided empirical wavelet transform for fault diagnosis of rolling element bearings

NASA Astrophysics Data System (ADS)

Wang, Dong; Zhao, Yang; Yi, Cai; Tsui, Kwok-Leung; Lin, Jianhui

2018-02-01

Rolling element bearings are widely used in various industrial machines, such as electric motors, generators, pumps, gearboxes, railway axles, turbines, and helicopter transmissions. Fault diagnosis of rolling element bearings is beneficial to preventing any unexpected accident and reducing economic loss. In the past years, many bearing fault detection methods have been developed. Recently, a new adaptive signal processing method called empirical wavelet transform attracts much attention from readers and engineers and its applications to bearing fault diagnosis have been reported. The main problem of empirical wavelet transform is that Fourier segments required in empirical wavelet transform are strongly dependent on the local maxima of the amplitudes of the Fourier spectrum of a signal, which connotes that Fourier segments are not always reliable and effective if the Fourier spectrum of the signal is complicated and overwhelmed by heavy noises and other strong vibration components. In this paper, sparsity guided empirical wavelet transform is proposed to automatically establish Fourier segments required in empirical wavelet transform for fault diagnosis of rolling element bearings. Industrial bearing fault signals caused by single and multiple railway axle bearing defects are used to verify the effectiveness of the proposed sparsity guided empirical wavelet transform. Results show that the proposed method can automatically discover Fourier segments required in empirical wavelet transform and reveal single and multiple railway axle bearing defects. Besides, some comparisons with three popular signal processing methods including ensemble empirical mode decomposition, the fast kurtogram and the fast spectral correlation are conducted to highlight the superiority of the proposed method.

Isorhynchophylline, a Potent Plant Alkaloid, Induces Apoptotic and Anti-Metastatic Effects in Human Hepatocellular Carcinoma Cells through the Modulation of Diverse Cell Signaling Cascades

PubMed Central

Lee, Hanwool; Baek, Seung Ho; Lee, Jong Hyun; Kim, Chulwon; Ko, Jeong-Hyeon; Lee, Seok-Geun; Chinnathambi, Arunachalam; Alharbi, Sulaiman Ali; Yang, Woong Mo; Um, Jae-Young; Sethi, Gautam; Ahn, Kwang Seok

2017-01-01

Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase). This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4), MMP-9 (Matrix metallopeptidase-9), and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells. PMID:28534824

Isorhynchophylline, a Potent Plant Alkaloid, Induces Apoptotic and Anti-Metastatic Effects in Human Hepatocellular Carcinoma Cells through the Modulation of Diverse Cell Signaling Cascades.

PubMed

Lee, Hanwool; Baek, Seung Ho; Lee, Jong Hyun; Kim, Chulwon; Ko, Jeong-Hyeon; Lee, Seok-Geun; Chinnathambi, Arunachalam; Alharbi, Sulaiman Ali; Yang, Woong Mo; Um, Jae-Young; Sethi, Gautam; Ahn, Kwang Seok

2017-05-19

Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase). This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4), MMP-9 (Matrix metallopeptidase-9), and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells.

Proteomic Profiling of Cranial (Superior) Cervical Ganglia Reveals Beta-Amyloid and Ubiquitin Proteasome System Perturbations in an Equine Multiple System Neuropathy.

PubMed

McGorum, Bruce C; Pirie, R Scott; Eaton, Samantha L; Keen, John A; Cumyn, Elizabeth M; Arnott, Danielle M; Chen, Wenzhang; Lamont, Douglas J; Graham, Laura C; Llavero Hurtado, Maica; Pemberton, Alan; Wishart, Thomas M

2015-11-01

Equine grass sickness (EGS) is an acute, predominantly fatal, multiple system neuropathy of grazing horses with reported incidence rates of ∼2%. An apparently identical disease occurs in multiple species, including but not limited to cats, dogs, and rabbits. Although the precise etiology remains unclear, ultrastructural findings have suggested that the primary lesion lies in the glycoprotein biosynthetic pathway of specific neuronal populations. The goal of this study was therefore to identify the molecular processes underpinning neurodegeneration in EGS. Here, we use a bottom-up approach beginning with the application of modern proteomic tools to the analysis of cranial (superior) cervical ganglion (CCG, a consistently affected tissue) from EGS-affected patients and appropriate control cases postmortem. In what appears to be the proteomic application of modern proteomic tools to equine neuronal tissues and/or to an inherent neurodegenerative disease of large animals (not a model of human disease), we identified 2,311 proteins in CCG extracts, with 320 proteins increased and 186 decreased by greater than 20% relative to controls. Further examination of selected proteomic candidates by quantitative fluorescent Western blotting (QFWB) and subcellular expression profiling by immunohistochemistry highlighted a previously unreported dysregulation in proteins commonly associated with protein misfolding/aggregation responses seen in a myriad of human neurodegenerative conditions, including but not limited to amyloid precursor protein (APP), microtubule associated protein (Tau), and multiple components of the ubiquitin proteasome system (UPS). Differentially expressed proteins eligible for in silico pathway analysis clustered predominantly into the following biofunctions: (1) diseases and disorders, including; neurological disease and skeletal and muscular disorders and (2) molecular and cellular functions, including cellular assembly and organization, cell-to-cell signaling and interaction (including epinephrine, dopamine, and adrenergic signaling and receptor function), and small molecule biochemistry. Interestingly, while the biofunctions identified in this study may represent pathways underpinning EGS-induced neurodegeneration, this is also the first demonstration of potential molecular conservation (including previously unreported dysregulation of the UPS and APP) spanning the degenerative cascades from an apparently unrelated condition of large animals, to small animal models with altered neuronal vulnerability, and human neurological conditions. Importantly, this study highlights the feasibility and benefits of applying modern proteomic techniques to veterinary investigations of neurodegenerative processes in diseases of large animals. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Multiple chimeric antigen receptors successfully target chondroitin sulfate proteoglycan 4 in several different cancer histologies and cancer stem cells

PubMed Central

2014-01-01

Background The development of immunotherapy has led to significant progress in the treatment of metastatic cancer, including the development of genetic engineering technologies that redirect lymphocytes to recognize and target a wide variety of tumor antigens. Chimeric antigen receptors (CARs) are hybrid proteins combining antibody recognition domains linked to T cell signaling elements. Clinical trials of CAR-transduced peripheral blood lymphocytes (PBL) have induced remission of both solid organ and hematologic malignancies. Chondroitin sulfate proteoglycan 4 (CSPG4) is a promising target antigen that is overexpressed in multiple cancer histologies including melanoma, triple-negative breast cancer, glioblastoma, mesothelioma and sarcoma. Methods CSPG4 expression in cancer cell lines was assayed using flow cytometry (FACS) and reverse-transcription PCR (RT-PCR). Immunohistochemistry was utilized to assay resected melanomas and normal human tissues (n = 30) for CSPG4 expression and a reverse-phase protein array comprising 94 normal tissue samples was also interrogated for CSPG4 expression. CARs were successfully constructed from multiple murine antibodies (225.28S, TP41.2, 149.53) using second generation (CD28.CD3ζ) signaling domains. CAR sequences were cloned into a gamma-retroviral vector with subsequent successful production of retroviral supernatant and PBL transduction. CAR efficacy was assayed by cytokine release and cytolysis following coculture with target cell lines. Additionally, glioblastoma stem cells were generated from resected human tumors, and CSPG4 expression was determined by RT-PCR and FACS. Results Immunohistochemistry demonstrated prominent CSPG4 expression in melanoma tumors, but failed to demonstrate expression in any of the 30 normal human tissues studied. Two of 94 normal tissue protein lysates were positive by protein array. CAR constructs demonstrated cytokine secretion and cytolytic function after co-culture with tumor cell lines from multiple different histologies, including melanoma, breast cancer, mesothelioma, glioblastoma and osteosarcoma. Furthermore, we report for the first time that CSPG4 is expressed on glioblastoma cancer stem cells (GSC) and demonstrate that anti-CSPG4 CAR-transduced T cells recognize and kill these GSC. Conclusions The functionality of multiple different CARs, with the widespread expression of CSPG4 on multiple malignancies, suggests that CSPG4 may be an attractive candidate tumor antigen for CAR-based immunotherapies using appropriate technology to limit possible off-tumor toxicity. PMID:25197555

Evolution of synthetic signaling scaffolds by recombination of modular protein domains.

PubMed

Lai, Andicus; Sato, Paloma M; Peisajovich, Sergio G

2015-06-19

Signaling scaffolds are proteins that interact via modular domains with multiple partners, regulating signaling networks in space and time and providing an ideal platform from which to alter signaling functions. However, to better exploit scaffolds for signaling engineering, it is necessary to understand the full extent of their modularity. We used a directed evolution approach to identify, from a large library of randomly shuffled protein interaction domains, variants capable of rescuing the signaling defect of a yeast strain in which Ste5, the scaffold in the mating pathway, had been deleted. After a single round of selection, we identified multiple synthetic scaffold variants with diverse domain architectures, able to mediate mating pathway activation in a pheromone-dependent manner. The facility with which this signaling network accommodates changes in scaffold architecture suggests that the mating signaling complex does not possess a single, precisely defined geometry into which the scaffold has to fit. These relaxed geometric constraints may facilitate the evolution of signaling networks, as well as their engineering for applications in synthetic biology.

Noise Suppression Based on Multi-Model Compositions Using Multi-Pass Search with Multi-Label N-gram Models

NASA Astrophysics Data System (ADS)

Jitsuhiro, Takatoshi; Toriyama, Tomoji; Kogure, Kiyoshi

We propose a noise suppression method based on multi-model compositions and multi-pass search. In real environments, input speech for speech recognition includes many kinds of noise signals. To obtain good recognized candidates, suppressing many kinds of noise signals at once and finding target speech is important. Before noise suppression, to find speech and noise label sequences, we introduce multi-pass search with acoustic models including many kinds of noise models and their compositions, their n-gram models, and their lexicon. Noise suppression is frame-synchronously performed using the multiple models selected by recognized label sequences with time alignments. We evaluated this method using the E-Nightingale task, which contains voice memoranda spoken by nurses during actual work at hospitals. The proposed method obtained higher performance than the conventional method.

Responds of Bone Cells to Microgravity: Ground-Based Research

NASA Astrophysics Data System (ADS)

Zhang, Jian; Li, Jingbao; Xu, Huiyun; Yang, Pengfei; Xie, Li; Qian, Airong; Zhao, Yong; Shang, Peng

2015-11-01

Severe loss of bone occurs due to long-duration spaceflight. Mechanical loading stimulates bone formation, while bone degradation happens under mechanical unloading. Bone remodeling is a dynamic process in which bone formation and bone resorption are tightly coupled. Increased bone resorption and decreased bone formation caused by reduced mechanical loading, generally result in disrupted bone remodeling. Bone remodeling is orchestrated by multiple bone cells including osteoblast, osteocyte, osteoclast and mesenchymal stem cell. It is yet not clear that how these bone cells sense altered gravity, translate physical stimulus into biochemical signals, and then regulate themselves structurally and functionally. In this paper, studies elucidating the bioeffects of microgravity on bone cells (osteoblast, osteocyte, osteoclast, mesenchymal stem cell) using various platforms including spaceflight and ground-based simulated microgravity were summarized. Promising gravity-sensitive signaling pathways and protein molecules were proposed.

Simvastatin Potently Induces Calcium-dependent Apoptosis of Human Leiomyoma Cells*

PubMed Central

Borahay, Mostafa A.; Kilic, Gokhan S.; Yallampalli, Chandrasekha; Snyder, Russell R.; Hankins, Gary D. V.; Al-Hendy, Ayman; Boehning, Darren

2014-01-01

Statins are drugs commonly used for the treatment of high plasma cholesterol levels. Beyond these well known lipid-lowering properties, they possess broad-reaching effects in vivo, including antitumor effects. Statins inhibit the growth of multiple tumors. However, the mechanisms remain incompletely understood. Here we show that simvastatin inhibits the proliferation of human leiomyoma cells. This was associated with decreased mitogen-activated protein kinase signaling and multiple changes in cell cycle progression. Simvastatin potently stimulated leiomyoma cell apoptosis in a manner mechanistically dependent upon apoptotic calcium release from voltage-gated calcium channels. Therefore, simvastatin possesses antitumor effects that are dependent upon the apoptotic calcium release machinery. PMID:25359773

Autapse-induced multiple stochastic resonances in a modular neuronal network

NASA Astrophysics Data System (ADS)

Yang, XiaoLi; Yu, YanHu; Sun, ZhongKui

2017-08-01

This study investigates the nontrivial effects of autapse on stochastic resonance in a modular neuronal network subjected to bounded noise. The resonance effect of autapse is detected by imposing a self-feedback loop with autaptic strength and autaptic time delay to each constituent neuron. Numerical simulations have demonstrated that bounded noise with the proper level of amplitude can induce stochastic resonance; moreover, the noise induced resonance dynamics can be significantly shaped by the autapse. In detail, for a specific range of autaptic strength, multiple stochastic resonances can be induced when the autaptic time delays are appropriately adjusted. These appropriately adjusted delays are detected to nearly approach integer multiples of the period of the external weak signal when the autaptic strength is very near zero; otherwise, they do not match the period of the external weak signal when the autaptic strength is slightly greater than zero. Surprisingly, in both cases, the differences between arbitrary two adjacent adjusted autaptic delays are always approximately equal to the period of the weak signal. The phenomenon of autaptic delay induced multiple stochastic resonances is further confirmed to be robust against the period of the external weak signal and the intramodule probability of subnetwork. These findings could have important implications for weak signal detection and information propagation in realistic neural systems.

Abnormal Glucose Metabolism in Alzheimer’s Disease: Relation to Autophagy/Mitophagy and Therapeutic Approaches

PubMed Central

Banerjee, Kalpita; Munshi, Soumyabrata; Frank, David E.; Gibson, Gary E.

2015-01-01

Diminished glucose metabolism accompanies many neurodegenerative diseases including Alzheimer’s disease. An understanding of the relation of these metabolic changes to the disease will enable development of novel therapeutic strategies. Following a metabolic challenge, cells generally conserve energy to preserve viability. This requires activation of many cellular repair/regenerative processes such as mitophagy/autophagy and fusion/fission. These responses may diminish cell function in the long term. Prolonged fission induces mitophagy/autophagy which promotes repair but if prolonged progresses to mitochondrial degradation. Abnormal glucose metabolism alters protein signaling including the release of proteins from the mitochondria or migration of proteins from the cytosol to the mitochondria or nucleus. This overview provides an insight into the different mechanisms of autophagy/mitophagy and mitochondrial dynamics in response to the diminished metabolism that occurs with diseases, especially neurodegenerative diseases such as Alzheimer's disease. The review discusses multiple aspects of mitochondrial responses including different signaling proteins and pathways of mitophagy and mitochondrial biogenesis. Improving cellular bioenergetics and mitochondrial dynamics will alter protein signaling and improve cellular/mitochondrial repair and regeneration. An understanding of these changes will suggest new therapeutic strategies. PMID:26077923

Signal uniformity of mammography systems and its impact on test results from contrast detail phantoms

NASA Astrophysics Data System (ADS)

Kaar, M.; Semturs, F.; Hummel, J.; Hoffmann, R.; Figl, M.

2015-03-01

Technical quality assurance (TQA) procedures for mammography systems usually include tests with a contrast-detail phantom. These phantoms contain multiple objects of varying dimensions arranged on a flat body. Exposures of the phantom are then evaluated by an observer, either human or software. One well-known issue of this method is that dose distribution is not uniform across the image area of any mammography system, mainly due to the heel effect. The purpose of this work is to investigate to what extent image quality differs across the detector plane. We analyze a total of 320 homogeneous mammography exposures from 32 radiology institutes. Systems of different models and manufacturers, both computed radiography (CR) and direct radiography (DR) are included. All images were taken from field installations operated within the nationwide Austrian mammography screening program, which includes mandatory continuous TQA. We calculate signal-to-noise ratios (SNR) for 15 regions of interest arranged to cover the area of the phantom. We define the 'signal range' of an image and compare this value categorized by technologies. We found the deviations of SNR greater in anterior-posterior than in lateral direction. SNR ranges are significantly higher for CR systems than for DR systems.

Ferritin protein nanocages use ion channels, catalytic sites, and nucleation channels to manage iron/oxygen chemistry.

PubMed

Theil, Elizabeth C

2011-04-01

The ferritin superfamily is composed of ancient, nanocage proteins with an internal cavity, 60% of total volume, that reversibly synthesize solid minerals of hydrated ferric oxide; the minerals are iron concentrates for cell nutrition as well as antioxidants due to ferrous and oxygen consumption during mineralization. The cages have multiple iron entry/exit channels, oxidoreductase enzyme sites, and, in eukaryotes, Fe(III)O nucleation channels with clustered exits that extend protein activity to include facilitated mineral growth. Ferritin protein cage differences include size, amino acid sequence, and location of the active sites, oxidant substrate and crystallinity of the iron mineral. Genetic regulation depends on iron and oxygen signals, which in animals includes direct ferrous signaling to RNA to release and to ubiquitin-ligases to degrade the protein repressors. Ferritin biosynthesis forms, with DNA, mRNA and the protein product, a feedback loop where the genetic signals are also protein substrates. The ferritin protein nanocages, which are required for normal iron homeostasis and are finding current use in the delivery of nanodrugs, novel nanomaterials, and nanocatalysts, are likely contributors to survival and success during the transition from anaerobic to aerobic life. Copyright © 2011. Published by Elsevier Ltd.

Ferritin Protein Nanocages Use Ion Channels, Catalytic Sites, and Nucleation Channels To Manage Iron/Oxygen Chemistry

PubMed Central

Theil, Elizabeth C.

2011-01-01

The ferritin superfamily is composed of ancient, nanocage proteins with an internal cavity, 60% of total volume, that reversibly synthesize solid minerals of hydrated ferric oxide; the minerals are iron concentrates for cell nutrition as well as antioxidants due to ferrous and oxygen consumption during mineralization. The cages have multiple iron entry/exit channels, oxidoreductase enzyme sites, and, in eukaryotes, Fe(III)O nucleation channels with clustered exits that extend protein activity to include facilitated mineral growth. Ferritin protein cage differences include size, amino acid sequence, and location of the active sites, oxidant substrate and crystallinity of the iron mineral. Genetic regulation depends on iron and oxygen signals, which in animals includes direct ferrous signaling to RNA to release and to ubiquitin-ligases to degrade the protein repressors. Ferritin biosynthesis forms, with DNA, mRNA and the protein product, a feedback loop where the genetic signals are also protein substrates. The ferritin protein nanocages, which are required for normal iron homeostasis and are finding current use in delivery of nanodrugs, novel nanomaterials, and nanocatalysts, are likely contributors to survival and success during the transition from anaerobic to aerobic life. PMID:21296609

Construction and Experimental Validation of a Petri Net Model of Wnt/β-Catenin Signaling.

PubMed

Jacobsen, Annika; Heijmans, Nika; Verkaar, Folkert; Smit, Martine J; Heringa, Jaap; van Amerongen, Renée; Feenstra, K Anton

2016-01-01

The Wnt/β-catenin signaling pathway is important for multiple developmental processes and tissue maintenance in adults. Consequently, deregulated signaling is involved in a range of human diseases including cancer and developmental defects. A better understanding of the intricate regulatory mechanism and effect of physiological (active) and pathophysiological (hyperactive) WNT signaling is important for predicting treatment response and developing novel therapies. The constitutively expressed CTNNB1 (commonly and hereafter referred to as β-catenin) is degraded by a destruction complex, composed of amongst others AXIN1 and GSK3. The destruction complex is inhibited during active WNT signaling, leading to β-catenin stabilization and induction of β-catenin/TCF target genes. In this study we investigated the mechanism and effect of β-catenin stabilization during active and hyperactive WNT signaling in a combined in silico and in vitro approach. We constructed a Petri net model of Wnt/β-catenin signaling including main players from the plasma membrane (WNT ligands and receptors), cytoplasmic effectors and the downstream negative feedback target gene AXIN2. We validated that our model can be used to simulate both active (WNT stimulation) and hyperactive (GSK3 inhibition) signaling by comparing our simulation and experimental data. We used this experimentally validated model to get further insights into the effect of the negative feedback regulator AXIN2 upon WNT stimulation and observed an attenuated β-catenin stabilization. We furthermore simulated the effect of APC inactivating mutations, yielding a stabilization of β-catenin levels comparable to the Wnt-pathway activities observed in colorectal and breast cancer. Our model can be used for further investigation and viable predictions of the role of Wnt/β-catenin signaling in oncogenesis and development.

Construction and Experimental Validation of a Petri Net Model of Wnt/β-Catenin Signaling

PubMed Central

Heijmans, Nika; Verkaar, Folkert; Smit, Martine J.; Heringa, Jaap

2016-01-01

The Wnt/β-catenin signaling pathway is important for multiple developmental processes and tissue maintenance in adults. Consequently, deregulated signaling is involved in a range of human diseases including cancer and developmental defects. A better understanding of the intricate regulatory mechanism and effect of physiological (active) and pathophysiological (hyperactive) WNT signaling is important for predicting treatment response and developing novel therapies. The constitutively expressed CTNNB1 (commonly and hereafter referred to as β-catenin) is degraded by a destruction complex, composed of amongst others AXIN1 and GSK3. The destruction complex is inhibited during active WNT signaling, leading to β-catenin stabilization and induction of β-catenin/TCF target genes. In this study we investigated the mechanism and effect of β-catenin stabilization during active and hyperactive WNT signaling in a combined in silico and in vitro approach. We constructed a Petri net model of Wnt/β-catenin signaling including main players from the plasma membrane (WNT ligands and receptors), cytoplasmic effectors and the downstream negative feedback target gene AXIN2. We validated that our model can be used to simulate both active (WNT stimulation) and hyperactive (GSK3 inhibition) signaling by comparing our simulation and experimental data. We used this experimentally validated model to get further insights into the effect of the negative feedback regulator AXIN2 upon WNT stimulation and observed an attenuated β-catenin stabilization. We furthermore simulated the effect of APC inactivating mutations, yielding a stabilization of β-catenin levels comparable to the Wnt-pathway activities observed in colorectal and breast cancer. Our model can be used for further investigation and viable predictions of the role of Wnt/β-catenin signaling in oncogenesis and development. PMID:27218469

High resolution, multiple-energy linear sweep detector for x-ray imaging

DOEpatents

Perez-Mendez, Victor; Goodman, Claude A.

1996-01-01

Apparatus for generating plural electrical signals in a single scan in response to incident X-rays received from an object. Each electrical signal represents an image of the object at a different range of energies of the incident X-rays. The apparatus comprises a first X-ray detector, a second X-ray detector stacked upstream of the first X-ray detector, and an X-ray absorber stacked upstream of the first X-ray detector. The X-ray absorber provides an energy-dependent absorption of the incident X-rays before they are incident at the first X-ray detector, but provides no absorption of the incident X-rays before they are incident at the second X-ray detector. The first X-ray detector includes a linear array of first pixels, each of which produces an electrical output in response to the incident X-rays in a first range of energies. The first X-ray detector also includes a circuit that generates a first electrical signal in response to the electrical output of each of the first pixels. The second X-ray detector includes a linear array of second pixels, each of which produces an electrical output in response to the incident X-rays in a second range of energies, broader than the first range of energies. The second X-ray detector also includes a circuit that generates a second electrical signal in response to the electrical output of each of the second pixels.

High resolution, multiple-energy linear sweep detector for x-ray imaging

DOEpatents

Perez-Mendez, V.; Goodman, C.A.

1996-08-20

Apparatus is disclosed for generating plural electrical signals in a single scan in response to incident X-rays received from an object. Each electrical signal represents an image of the object at a different range of energies of the incident X-rays. The apparatus comprises a first X-ray detector, a second X-ray detector stacked upstream of the first X-ray detector, and an X-ray absorber stacked upstream of the first X-ray detector. The X-ray absorber provides an energy-dependent absorption of the incident X-rays before they are incident at the first X-ray detector, but provides no absorption of the incident X-rays before they are incident at the second X-ray detector. The first X-ray detector includes a linear array of first pixels, each of which produces an electrical output in response to the incident X-rays in a first range of energies. The first X-ray detector also includes a circuit that generates a first electrical signal in response to the electrical output of each of the first pixels. The second X-ray detector includes a linear array of second pixels, each of which produces an electrical output in response to the incident X-rays in a second range of energies, broader than the first range of energies. The second X-ray detector also includes a circuit that generates a second electrical signal in response to the electrical output of each of the second pixels. 12 figs.

Genome-wide network analysis of Wnt signaling in three pediatric cancers

NASA Astrophysics Data System (ADS)

Bao, Ju; Lee, Ho-Jin; Zheng, Jie J.

2013-10-01

Genomic structural alteration is common in pediatric cancers, and analysis of data generated by the Pediatric Cancer Genome Project reveals such tumor-related alterations in many Wnt signaling-associated genes. Most pediatric cancers are thought to arise within developing tissues that undergo substantial expansion during early organ formation, growth and maturation, and Wnt signaling plays an important role in this development. We examined three pediatric tumors--medullobastoma, early T-cell precursor acute lymphoblastic leukemia, and retinoblastoma--that show multiple genomic structural variations within Wnt signaling pathways. We mathematically modeled this pathway to investigate the effects of cancer-related structural variations on Wnt signaling. Surprisingly, we found that an outcome measure of canonical Wnt signaling was consistently similar in matched cancer cells and normal cells, even in the context of different cancers, different mutations, and different Wnt-related genes. Our results suggest that the cancer cells maintain a normal level of Wnt signaling by developing multiple mutations.

Complex regulation of HSC emergence by the Notch signaling pathway

PubMed Central

Butko, Emerald; Pouget, Claire; Traver, David

2016-01-01

Hematopoietic stem cells are formed during embryonic development, and serve as the foundation of the definitive blood program for life. Notch signaling has been well established as an essential direct contributor to HSC specification. However, several recent studies have indicated that the contribution of Notch signaling is complex. HSC specification requires multiple Notch signaling inputs, some received directly by hematopoietic precursors, and others that occur indirectly within neighboring somites. Of note, proinflammatory signals provided by primitive myeloid cells are needed for HSC specification via upregulation of the Notch pathway in hemogenic endothelium. In addition to multiple requirements for Notch activation, recent studies indicate that Notch signaling must subsequently be repressed to permit HSC emergence. Finally, Notch must then be reactivated to maintain HSC fate. In this review, we discuss the growing understanding of the dynamic contributions of Notch signaling to the establishment of hematopoiesis during development. PMID:26586199

Neutron Detector Signal Processing to Calculate the Effective Neutron Multiplication Factor of Subcritical Assemblies

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

Talamo, Alberto; Gohar, Yousry

2016-06-01

This report describes different methodologies to calculate the effective neutron multiplication factor of subcritical assemblies by processing the neutron detector signals using MATLAB scripts. The subcritical assembly can be driven either by a spontaneous fission neutron source (e.g. californium) or by a neutron source generated from the interactions of accelerated particles with target materials. In the latter case, when the particle accelerator operates in a pulsed mode, the signals are typically stored into two files. One file contains the time when neutron reactions occur and the other contains the times when the neutron pulses start. In both files, the timemore » is given by an integer representing the number of time bins since the start of the counting. These signal files are used to construct the neutron count distribution from a single neutron pulse. The built-in functions of MATLAB are used to calculate the effective neutron multiplication factor through the application of the prompt decay fitting or the area method to the neutron count distribution. If the subcritical assembly is driven by a spontaneous fission neutron source, then the effective multiplication factor can be evaluated either using the prompt neutron decay constant obtained from Rossi or Feynman distributions or the Modified Source Multiplication (MSM) method.« less

FPGA-Based Filterbank Implementation for Parallel Digital Signal Processing

NASA Technical Reports Server (NTRS)

Berner, Stephan; DeLeon, Phillip

1999-01-01

One approach to parallel digital signal processing decomposes a high bandwidth signal into multiple lower bandwidth (rate) signals by an analysis bank. After processing, the subband signals are recombined into a fullband output signal by a synthesis bank. This paper describes an implementation of the analysis and synthesis banks using (Field Programmable Gate Arrays) FPGAs.

Application of a multiple scattering model to estimate optical depth, lidar ratio and ice crystal effective radius of cirrus clouds observed with lidar.

NASA Astrophysics Data System (ADS)

Gouveia, Diego; Baars, Holger; Seifert, Patric; Wandinger, Ulla; Barbosa, Henrique; Barja, Boris; Artaxo, Paulo; Lopes, Fabio; Landulfo, Eduardo; Ansmann, Albert

2018-04-01

Lidar measurements of cirrus clouds are highly influenced by multiple scattering (MS). We therefore developed an iterative approach to correct elastic backscatter lidar signals for multiple scattering to obtain best estimates of single-scattering cloud optical depth and lidar ratio as well as of the ice crystal effective radius. The approach is based on the exploration of the effect of MS on the molecular backscatter signal returned from above cloud top.

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.

Chirp-free optical return-to-zero modulation based on a single microring resonator.

PubMed

Sun, Lili; Ye, Tong; Wang, Xiaowen; Zhou, Linjie; Chen, Jianping

2012-03-26

This paper proposes a chirp-free optical return-to-zero (RZ) modulator using a double coupled microring resonator. Optical RZ modulation is achieved by applying a clock (CLK) driving signal to the input coupling region and a non-return-to-zero (NRZ) driving signal to the output coupling region. Static and time-domain coupled-mode theory (CMT) based dynamic analyse are performed to theoretically investigate its performance in RZ modulation. The criteria to realize RZ modulation are deduced. Various RZ modulation formats, including RZ phase-shift-keying (RZ-PSK), carrier-suppressed RZ (CSRZ), and RZ intensity modulation formats, can be implemented by using CLK and NRZ signals with different combinations of polarities. Numerical simulations are performed and the feasibility of our modulator at 10 Gbit/s for the multiple RZ modulation formats is verified.

Structure of the Repulsive Guidance Molecule (RGM)—Neogenin Signaling Hub

PubMed Central

Bell, Christian H.; Bishop, Benjamin; Tang, Chenxiang; Gilbert, Robert J.C.; Aricescu, A. Radu; Pasterkamp, R. Jeroen; Siebold, Christian

2016-01-01

Repulsive guidance molecule family members (RGMs) control fundamental and diverse cellular processes, including motility and adhesion, immune cell regulation, and systemic iron metabolism. However, it is not known how RGMs initiate signaling through their common cell-surface receptor, neogenin (NEO1). Here, we present crystal structures of the NEO1 RGM-binding region and its complex with human RGMB (also called dragon). The RGMB structure reveals a previously unknown protein fold and a functionally important autocatalytic cleavage mechanism and provides a framework to explain numerous disease-linked mutations in RGMs. In the complex, two RGMB ectodomains conformationally stabilize the juxtamembrane regions of two NEO1 receptors in a pH-dependent manner. We demonstrate that all RGM-NEO1 complexes share this architecture, which therefore represents the core of multiple signaling pathways. PMID:23744777

Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses.

PubMed

Wasser, Catherine R; Herz, Joachim

2017-01-27

Over half a century ago, D. S. Falconer first reported a mouse with a reeling gate. Four decades later, the Reln gene was isolated and identified as the cause of the reeler phenotype. Initial studies found that loss of Reelin, a large, secreted glycoprotein encoded by the Reln gene, results in abnormal neuronal layering throughout several regions of the brain. In the years since, the known functions of Reelin signaling in the brain have expanded to include multiple postdevelopmental neuromodulatory roles, revealing an ever increasing body of evidence to suggest that Reelin signaling is a critical player in the modulation of synaptic function. In writing this review, we intend to highlight the most fundamental aspects of Reelin signaling and integrate how these various neuromodulatory effects shape and protect synapses. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

A CRISPR-Based Toolbox for Studying T Cell Signal Transduction

PubMed Central

Chi, Shen; Weiss, Arthur; Wang, Haopeng

2016-01-01

CRISPR/Cas9 system is a powerful technology to perform genome editing in a variety of cell types. To facilitate the application of Cas9 in mapping T cell signaling pathways, we generated a toolbox for large-scale genetic screens in human Jurkat T cells. The toolbox has three different Jurkat cell lines expressing distinct Cas9 variants, including wild-type Cas9, dCas9-KRAB, and sunCas9. We demonstrated that the toolbox allows us to rapidly disrupt endogenous gene expression at the DNA level and to efficiently repress or activate gene expression at the transcriptional level. The toolbox, in combination with multiple currently existing genome-wide sgRNA libraries, will be useful to systematically investigate T cell signal transduction using both loss-of-function and gain-of-function genetic screens. PMID:27057542

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;

Measuring the scale dependence of intrinsic alignments using multiple shear estimates

NASA Astrophysics Data System (ADS)

Leonard, C. Danielle; Mandelbaum, Rachel

2018-06-01

We present a new method for measuring the scale dependence of the intrinsic alignment (IA) contamination to the galaxy-galaxy lensing signal, which takes advantage of multiple shear estimation methods applied to the same source galaxy sample. By exploiting the resulting correlation of both shape noise and cosmic variance, our method can provide an increase in the signal-to-noise of the measured IA signal as compared to methods which rely on the difference of the lensing signal from multiple photometric redshift bins. For a galaxy-galaxy lensing measurement which uses LSST sources and DESI lenses, the signal-to-noise on the IA signal from our method is predicted to improve by a factor of ˜2 relative to the method of Blazek et al. (2012), for pairs of shear estimates which yield substantially different measured IA amplitudes and highly correlated shape noise terms. We show that statistical error necessarily dominates the measurement of intrinsic alignments using our method. We also consider a physically motivated extension of the Blazek et al. (2012) method which assumes that all nearby galaxy pairs, rather than only excess pairs, are subject to IA. In this case, the signal-to-noise of the method of Blazek et al. (2012) is improved.

A dynamic programming approach for the alignment of signal peaks in multiple gas chromatography-mass spectrometry experiments.

PubMed

Robinson, Mark D; De Souza, David P; Keen, Woon Wai; Saunders, Eleanor C; McConville, Malcolm J; Speed, Terence P; Likić, Vladimir A

2007-10-29

Gas chromatography-mass spectrometry (GC-MS) is a robust platform for the profiling of certain classes of small molecules in biological samples. When multiple samples are profiled, including replicates of the same sample and/or different sample states, one needs to account for retention time drifts between experiments. This can be achieved either by the alignment of chromatographic profiles prior to peak detection, or by matching signal peaks after they have been extracted from chromatogram data matrices. Automated retention time correction is particularly important in non-targeted profiling studies. A new approach for matching signal peaks based on dynamic programming is presented. The proposed approach relies on both peak retention times and mass spectra. The alignment of more than two peak lists involves three steps: (1) all possible pairs of peak lists are aligned, and similarity of each pair of peak lists is estimated; (2) the guide tree is built based on the similarity between the peak lists; (3) peak lists are progressively aligned starting with the two most similar peak lists, following the guide tree until all peak lists are exhausted. When two or more experiments are performed on different sample states and each consisting of multiple replicates, peak lists within each set of replicate experiments are aligned first (within-state alignment), and subsequently the resulting alignments are aligned themselves (between-state alignment). When more than two sets of replicate experiments are present, the between-state alignment also employs the guide tree. We demonstrate the usefulness of this approach on GC-MS metabolic profiling experiments acquired on wild-type and mutant Leishmania mexicana parasites. We propose a progressive method to match signal peaks across multiple GC-MS experiments based on dynamic programming. A sensitive peak similarity function is proposed to balance peak retention time and peak mass spectra similarities. This approach can produce the optimal alignment between an arbitrary number of peak lists, and models explicitly within-state and between-state peak alignment. The accuracy of the proposed method was close to the accuracy of manually-curated peak matching, which required tens of man-hours for the analyzed data sets. The proposed approach may offer significant advantages for processing of high-throughput metabolomics data, especially when large numbers of experimental replicates and multiple sample states are analyzed.

Multiple Signal Classification for Gravitational Wave Burst Search

NASA Astrophysics Data System (ADS)

Cao, Junwei; He, Zhengqi

2013-01-01

This work is mainly focused on the application of the multiple signal classification (MUSIC) algorithm for gravitational wave burst search. This algorithm extracts important gravitational wave characteristics from signals coming from detectors with arbitrary position, orientation and noise covariance. In this paper, the MUSIC algorithm is described in detail along with the necessary adjustments required for gravitational wave burst search. The algorithm's performance is measured using simulated signals and noise. MUSIC is compared with the Q-transform for signal triggering and with Bayesian analysis for direction of arrival (DOA) estimation, using the Ω-pipeline. Experimental results show that MUSIC has a lower resolution but is faster. MUSIC is a promising tool for real-time gravitational wave search for multi-messenger astronomy.

Intermolecular correlations are necessary to explain diffuse scattering from protein crystals

DOE PAGES

Peck, Ariana; Poitevin, Frederic; Lane, Thomas Joseph

2018-02-21

Conformational changes drive protein function, including catalysis, allostery, and signaling. X-ray diffuse scattering from protein crystals has frequently been cited as a probe of these correlated motions, with significant potential to advance our understanding of biological dynamics. However, recent work challenged this prevailing view, suggesting instead that diffuse scattering primarily originates from rigid body motions and could therefore be applied to improve structure determination. To investigate the nature of the disorder giving rise to diffuse scattering, and thus the potential applications of this signal, a diverse repertoire of disorder models was assessed for its ability to reproduce the diffuse signalmore » reconstructed from three protein crystals. This comparison revealed that multiple models of intramolecular conformational dynamics, including ensemble models inferred from the Bragg data, could not explain the signal. Models of rigid body or short-range liquid-like motions, in which dynamics are confined to the biological unit, showed modest agreement with the diffuse maps, but were unable to reproduce experimental features indicative of long-range correlations. Extending a model of liquid-like motions to include disorder across neighboring proteins in the crystal significantly improved agreement with all three systems and highlighted the contribution of intermolecular correlations to the observed signal. These findings anticipate a need to account for intermolecular disorder in order to advance the interpretation of diffuse scattering to either extract biological motions or aid structural inference.« less

Signaling through protein kinases and transcriptional regulators in Candida albicans.

PubMed

Dhillon, Navneet K; Sharma, Sadhna; Khuller, G K

2003-01-01

The human fungal pathogen Candida albicans switches from a budding yeast form to a polarized hyphal form in response to various external signals. This morphogenetic switching has been implicated in the development of pathogenicity. Several signaling pathways that regulate morphogenesis have been identified, including various transcription factors that either activate or repress hypha-specific genes. Two well-characterized pathways include the MAP kinase cascade and cAMP-dependent protein kinase pathway that regulate the transcription factors Cph1p and Efg1p, respectively. cAMP also appears to interplay with other second messengers: Ca2+, inositol tri-phosphates in regulating yeast-hyphal transition. Other, less-characterized pathways include two component histidine kinases, cyclin-dependent kinase pathway, and condition specific pathways such as pH and embedded growth conditions. Nrg1 and Rfg1 function as transcriptional repressors of hyphal genes via recruitment of Tup1 co-repressor complex. Different upstream signals converge into a common downstream output during hyphal switch. The levels of expression of several genes have been shown to be associated with hyphal morphogenesis rather than with a specific hypha-inducing condition. Hyphal development is also linked to the expression of a range of other virulence factors. This review explains the relative contribution of multiple pathways that could be used by Candida albican cells to sense subtle differences in the growth conditions of its native host environment.

Intermolecular correlations are necessary to explain diffuse scattering from protein crystals

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

Peck, Ariana; Poitevin, Frederic; Lane, Thomas Joseph

Conformational changes drive protein function, including catalysis, allostery, and signaling. X-ray diffuse scattering from protein crystals has frequently been cited as a probe of these correlated motions, with significant potential to advance our understanding of biological dynamics. However, recent work challenged this prevailing view, suggesting instead that diffuse scattering primarily originates from rigid body motions and could therefore be applied to improve structure determination. To investigate the nature of the disorder giving rise to diffuse scattering, and thus the potential applications of this signal, a diverse repertoire of disorder models was assessed for its ability to reproduce the diffuse signalmore » reconstructed from three protein crystals. This comparison revealed that multiple models of intramolecular conformational dynamics, including ensemble models inferred from the Bragg data, could not explain the signal. Models of rigid body or short-range liquid-like motions, in which dynamics are confined to the biological unit, showed modest agreement with the diffuse maps, but were unable to reproduce experimental features indicative of long-range correlations. Extending a model of liquid-like motions to include disorder across neighboring proteins in the crystal significantly improved agreement with all three systems and highlighted the contribution of intermolecular correlations to the observed signal. These findings anticipate a need to account for intermolecular disorder in order to advance the interpretation of diffuse scattering to either extract biological motions or aid structural inference.« less

Power-efficient method for IM-DD optical transmission of multiple OFDM signals.

PubMed

Effenberger, Frank; Liu, Xiang

2015-05-18

We propose a power-efficient method for transmitting multiple frequency-division multiplexed (FDM) orthogonal frequency-division multiplexing (OFDM) signals in intensity-modulation direct-detection (IM-DD) optical systems. This method is based on quadratic soft clipping in combination with odd-only channel mapping. We show, both analytically and experimentally, that the proposed approach is capable of improving the power efficiency by about 3 dB as compared to conventional FDM OFDM signals under practical bias conditions, making it a viable solution in applications such as optical fiber-wireless integrated systems where both IM-DD optical transmission and OFDM signaling are important.

Full Duplex, Spread Spectrum Radio System

NASA Technical Reports Server (NTRS)

Harvey, Bruce A.

2000-01-01

The goal of this project was to support the development of a full duplex, spread spectrum voice communications system. The assembly and testing of a prototype system consisting of a Harris PRISM spread spectrum radio, a TMS320C54x signal processing development board and a Zilog Z80180 microprocessor was underway at the start of this project. The efforts under this project were the development of multiple access schemes, analysis of full duplex voice feedback delays, and the development and analysis of forward error correction (FEC) algorithms. The multiple access analysis involved the selection between code division multiple access (CDMA), frequency division multiple access (FDMA) and time division multiple access (TDMA). Full duplex voice feedback analysis involved the analysis of packet size and delays associated with full loop voice feedback for confirmation of radio system performance. FEC analysis included studies of the performance under the expected burst error scenario with the relatively short packet lengths, and analysis of implementation in the TMS320C54x digital signal processor. When the capabilities and the limitations of the components used were considered, the multiple access scheme chosen was a combination TDMA/FDMA scheme that will provide up to eight users on each of three separate frequencies. Packets to and from each user will consist of 16 samples at a rate of 8,000 samples per second for a total of 2 ms of voice information. The resulting voice feedback delay will therefore be 4 - 6 ms. The most practical FEC algorithm for implementation was a convolutional code with a Viterbi decoder. Interleaving of the bits of each packet will be required to offset the effects of burst errors.

Phosphoinositide protein kinase PDPK1 is a crucial cell signaling mediator in multiple myeloma.

PubMed

Chinen, Yoshiaki; Kuroda, Junya; Shimura, Yuji; Nagoshi, Hisao; Kiyota, Miki; Yamamoto-Sugitani, Mio; Mizutani, Shinsuke; Sakamoto, Natsumi; Ri, Masaki; Kawata, Eri; Kobayashi, Tsutomu; Matsumoto, Yosuke; Horiike, Shigeo; Iida, Shinsuke; Taniwaki, Masafumi

2014-12-15

Multiple myeloma is a cytogenetically/molecularly heterogeneous hematologic malignancy that remains mostly incurable, and the identification of a universal and relevant therapeutic target molecule is essential for the further development of therapeutic strategy. Herein, we identified that 3-phosphoinositide-dependent protein kinase 1 (PDPK1), a serine threonine kinase, is expressed and active in all eleven multiple myeloma-derived cell lines examined regardless of the type of cytogenetic abnormality, the mutation state of RAS and FGFR3 genes, or the activation state of ERK and AKT. Our results revealed that PDPK1 is a pivotal regulator of molecules that are essential for myelomagenesis, such as RSK2, AKT, c-MYC, IRF4, or cyclin Ds, and that PDPK1 inhibition caused the growth inhibition and the induction of apoptosis with the activation of BIM and BAD, and augmented the in vitro cytotoxic effects of antimyeloma agents in myeloma cells. In the clinical setting, PDPK1 was active in myeloma cells of approximately 90% of symptomatic patients at diagnosis, and the smaller population of patients with multiple myeloma exhibiting myeloma cells without active PDPK1 showed a significantly less frequent proportion of the disease stage III by the International Staging System and a significantly more favorable prognosis, including the longer overall survival period and the longer progression-free survival period by bortezomib treatment, than patients with active PDPK1, suggesting that PDPK1 activation accelerates the disease progression and the resistance to treatment in multiple myeloma. Our study demonstrates that PDPK1 is a potent and a universally targetable signaling mediator in multiple myeloma regardless of the types of cytogenetic/molecular profiles. ©2014 American Association for Cancer Research.

Fiber-wireless transmission system of 108  Gb/sdata over 80 km fiber and 2×2multiple-input multiple-output wireless links at 100 GHz W-band frequency.

PubMed

Li, Xinying; Dong, Ze; Yu, Jianjun; Chi, Nan; Shao, Yufeng; Chang, G K

2012-12-15

We experimentally demonstrate a seamlessly integrated fiber-wireless system that delivers a 108  Gb/s signal through 80 km fiber and 1 m wireless transport over free space at 100 GHz adopting polarization-division-multiplexing quadrature-phase-shift-keying (PDM-QPSK) modulation and heterodyning coherent detection. The X- and Y-polarization components of the optical PDM-QPSK baseband signal are simultaneously upconverted to 100 GHz wireless carrier by optical polarization-diversity heterodyne beating, and then independently transmitted and received by two pairs of transmitter and receiver antennas, which form a 2×2 multiple-input multiple-output wireless link. At the wireless receiver, two-stage downconversion is performed firstly in the analog domain based on balanced mixer and sinusoidal radio frequency signal, and then in the digital domain based on digital signal processing (DSP). Polarization demultiplexing is realized by the constant modulus algorithm in the DSP part at the receiver. The bit-error ratio for the 108  Gb/s PDM-QPSK signal is less than the pre-forward-error-correction threshold of 3.8×10(-3) after both 1 m wireless delivery at 100 GHz and 80 km single-mode fiber-28 transmission. To our knowledge, this is the first demonstration to realize 100  Gb/s signal delivery through both fiber and wireless links at 100 GHz.

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.

Improving recovery of ECG signal with deterministic guarantees using split signal for multiple supports of matching pursuit (SS-MSMP) algorithm.

PubMed

Tawfic, Israa Shaker; Kayhan, Sema Koc

2017-02-01

Compressed sensing (CS) is a new field used for signal acquisition and design of sensor that made a large drooping in the cost of acquiring sparse signals. In this paper, new algorithms are developed to improve the performance of the greedy algorithms. In this paper, a new greedy pursuit algorithm, SS-MSMP (Split Signal for Multiple Support of Matching Pursuit), is introduced and theoretical analyses are given. The SS-MSMP is suggested for sparse data acquisition, in order to reconstruct analog and efficient signals via a small set of general measurements. This paper proposes a new fast method which depends on a study of the behavior of the support indices through picking the best estimation of the corrosion between residual and measurement matrix. The term multiple supports originates from an algorithm; in each iteration, the best support indices are picked based on maximum quality created by discovering correlation for a particular length of support. We depend on this new algorithm upon our previous derivative of halting condition that we produce for Least Support Orthogonal Matching Pursuit (LS-OMP) for clear and noisy signal. For better reconstructed results, SS-MSMP algorithm provides the recovery of support set for long signals such as signals used in WBAN. Numerical experiments demonstrate that the new suggested algorithm performs well compared to existing algorithms in terms of many factors used for reconstruction performance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Swallow segmentation with artificial neural networks and multi-sensor fusion.

PubMed

Lee, Joon; Steele, Catriona M; Chau, Tom

2009-11-01

Swallow segmentation is a critical precursory step to the analysis of swallowing signal characteristics. In an effort to automatically segment swallows, we investigated artificial neural networks (ANN) with information from cervical dual-axis accelerometry, submental MMG, and nasal airflow. Our objectives were (1) to investigate the relationship between segmentation performance and the number of signal sources and (2) to identify the signals or signal combinations most useful for swallow segmentation. Signals were acquired from 17 healthy adults in both discrete and continuous swallowing tasks using five stimuli. Training and test feature vectors were constructed with variances from single or multiple signals, estimated within 200 ms moving windows with 50% overlap. Corresponding binary target labels (swallow or non-swallow) were derived by manual segmentation. A separate 3-layer ANN was trained for each participant-signal combination, and all possible signal combinations were investigated. As more signal sources were included, segmentation performance improved in terms of sensitivity, specificity, accuracy, and adjusted accuracy. The combination of all four signal sources achieved the highest mean accuracy and adjusted accuracy of 88.5% and 89.6%, respectively. A-P accelerometry proved to be the most discriminatory source, while the inclusion of MMG or nasal airflow resulted in the least performance improvement. These findings suggest that an ANN, multi-sensor fusion approach to segmentation is worthy of further investigation in swallowing studies.

Dance band on the Titanic: biomechanical signaling in cardiac hypertrophy.

PubMed

Sussman, Mark A; McCulloch, Andrew; Borg, Thomas K

2002-11-15

Biomechanical signaling is a complex interaction of both intracellular and extracellular components. Both passive and active components are involved in the extracellular environment to signal through specific receptors to multiple signaling pathways. This review provides an overview of extracellular matrix, specific receptors, and signaling pathways for biomechanical stimulation in cardiac hypertrophy.

Method and apparatus for enhancing microchannel plate data

DOEpatents

Thoe, R.S.

1983-10-24

A method and apparatus for determining centroid channel locations are disclosed for use in a system activated by one or more multichannel plates and including a linear diode array providing channels of information 1, 2, ...,n, ..., N containing signal amplitudes A/sub n/. A source of analog A/sub n/ signals, and a source of digital clock signals n, are provided. Non-zero A/sub n/ values are detected in a discriminator. A digital signal representing p, the value of n immediately preceding that whereat A/sub n/ takes its first non-zero value, is generated in a scaler. The analog A/sub n/ signals are converted to digital in an analog to digital converter. The digital A/sub n/ signals are added to produce a digital ..sigma..A/sub n/ signal in a full adder. Digital 1, 2, ..., m signals representing the number of non-zero A/sub n/ are produced by a discriminator pulse counter. Digital signals representing 1 A/sub p+1/, 2 A/sub p+2/, ..., m A/sub p+m/ are produced by pairwise multiplication in multiplier. These signal are added in multiplier summer to produce a digital ..sigma..nA/sub n/ - p..sigma..A/sub n/ signal. This signal is divided by the digital ..sigma..A/sub n/ signal in divider to provide a digital (..sigma..nA/sub n//..sigma..A/sub n/) -p signal. Finally, this last signal is added to the digital p signal in an offset summer to provide ..sigma..nA/sub n//..sigma..A/sub n/, the centroid channel locations.

Real Time Location of Targets in Cluttered Environments

DTIC Science & Technology

2014-03-13

7 Return Signal computation from a single wind turbine ...7 Return Signal From Multiple Wind Turbines With and Without Aircraft...signals to the far field. 2. Validated using analytical signals. 3. Inner field scattering from a wind turbine and aircraft is computed 4. An

Multichannel microformulators for massively parallel machine learning and automated design of biological experiments

NASA Astrophysics Data System (ADS)

Wikswo, John; Kolli, Aditya; Shankaran, Harish; Wagoner, Matthew; Mettetal, Jerome; Reiserer, Ronald; Gerken, Gregory; Britt, Clayton; Schaffer, David

Genetic, proteomic, and metabolic networks describing biological signaling can have 102 to 103 nodes. Transcriptomics and mass spectrometry can quantify 104 different dynamical experimental variables recorded from in vitro experiments with a time resolution approaching 1 s. It is difficult to infer metabolic and signaling models from such massive data sets, and it is unlikely that causality can be determined simply from observed temporal correlations. There is a need to design and apply specific system perturbations, which will be difficult to perform manually with 10 to 102 externally controlled variables. Machine learning and optimal experimental design can select an experiment that best discriminates between multiple conflicting models, but a remaining problem is to control in real time multiple variables in the form of concentrations of growth factors, toxins, nutrients and other signaling molecules. With time-division multiplexing, a microfluidic MicroFormulator (μF) can create in real time complex mixtures of reagents in volumes suitable for biological experiments. Initial 96-channel μF implementations control the exposure profile of cells in a 96-well plate to different temporal profiles of drugs; future experiments will include challenge compounds. Funded in part by AstraZeneca, NIH/NCATS HHSN271201600009C and UH3TR000491, and VIIBRE.

The Role of Th17 in Neuroimmune Disorders: Target for CAM Therapy. Part I.

PubMed

Vojdani, Aristo; Lambert, Jama

2011-01-01

CD4(+) effector cells, based on cytokine production, nuclear receptors and signaling pathways, have been categorized into four subsets. T-helper-1 cells produce IFN-γ, TNF-β, lymphotoxin and IL-10; T-helper-2 cells produce IL-4, IL-5, IL-10, IL-13, IL-21 and IL-31; T-helper-3, or regulatory T-cells, produce IL-10, TGF-β and IL-35; and the recently discovered T-helper-17 cell produces IL-17, IL-17A, IL-17F, IL-21, IL-26 and CCL20. By producing IL-17 and other signaling molecules, Th17 contributes to the pathogenesis of multiple autoimmune diseases including allergic inflammation, rheumatoid arthritis, autoimmune gastritis, inflammatory bowel disease, psoriasis and multiple sclerosis. In this article, we review the differential regulation of inflammation in different tissues with a major emphasis on enhancement of neuroinflammation by local production of IL-17 in the brain. By understanding the role of pathogenic factors in the induction of autoimmune diseases by Th17 cells, CAM practitioners will be able to design CAM therapies targeting Th17 and associated cytokine activities and signaling pathways to repair the intestinal and blood-brain barriers for their patients with autoimmunities, in particular, those with neuroinflammation and neurodegeneration.

Enzyme-regulated the changes of pH values for assembling a colorimetric and multistage interconnection logic network with multiple readouts.

PubMed

Huang, Yanyan; Ran, Xiang; Lin, Youhui; Ren, Jinsong; Qu, Xiaogang

2015-04-22

Based on enzymatic reactions-triggered changes of pH values and biocomputing, a novel and multistage interconnection biological network with multiple easy-detectable signal outputs has been developed. Compared with traditional chemical computing, the enzyme-based biological system could overcome the interference between reactions or the incompatibility of individual computing gates and offer a unique opportunity to assemble multicomponent/multifunctional logic circuitries. Our system included four enzyme inputs: β-galactosidase (β-gal), glucose oxidase (GOx), esterase (Est) and urease (Ur). With the assistance of two signal transducers (gold nanoparticles and acid-base indicators) or pH meter, the outputs of the biological network could be conveniently read by the naked eyes. In contrast to current methods, the approach present here could realize cost-effective, label-free and colorimetric logic operations without complicated instrument. By designing a series of Boolean logic operations, we could logically make judgment of the compositions of the samples on the basis of visual output signals. Our work offered a promising paradigm for future biological computing technology and might be highly useful in future intelligent diagnostics, prodrug activation, smart drug delivery, process control, and electronic applications. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2013-11-15

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

Multiple-hypothesis multiple-model line tracking

NASA Astrophysics Data System (ADS)

Pace, Donald W.; Owen, Mark W.; Cox, Henry

2000-07-01

Passive sonar signal processing generally includes tracking of narrowband and/or broadband signature components observed on a Lofargram or on a Bearing-Time-Record (BTR) display. Fielded line tracking approaches to date have been recursive and single-hypthesis-oriented Kalman- or alpha-beta filters, with no mechanism for considering tracking alternatives beyond the most recent scan of measurements. While adaptivity is often built into the filter to handle changing track dynamics, these approaches are still extensions of single target tracking solutions to multiple target tracking environment. This paper describes an application of multiple-hypothesis, multiple target tracking technology to the sonar line tracking problem. A Multiple Hypothesis Line Tracker (MHLT) is developed which retains the recursive minimum-mean-square-error tracking behavior of a Kalman Filter in a maximum-a-posteriori delayed-decision multiple hypothesis context. Multiple line track filter states are developed and maintained using the interacting multiple model (IMM) state representation. Further, the data association and assignment problem is enhanced by considering line attribute information (line bandwidth and SNR) in addition to beam/bearing and frequency fit. MHLT results on real sonar data are presented to demonstrate the benefits of the multiple hypothesis approach. The utility of the system in cluttered environments and particularly in crossing line situations is shown.

Bacterial effectors target the common signaling partner BAK1 to disrupt multiple MAMP receptor-signaling complexes and impede plant immunity.

PubMed

Shan, Libo; He, Ping; Li, Jianming; Heese, Antje; Peck, Scott C; Nürnberger, Thorsten; Martin, Gregory B; Sheen, Jen

2008-07-17

Successful pathogens have evolved strategies to interfere with host immune systems. For example, the ubiquitous plant pathogen Pseudomonas syringae injects two sequence-distinct effectors, AvrPto and AvrPtoB, to intercept convergent innate immune responses stimulated by multiple microbe-associated molecular patterns (MAMPs). However, the direct host targets and precise molecular mechanisms of bacterial effectors remain largely obscure. We show that AvrPto and AvrPtoB bind the Arabidopsis receptor-like kinase BAK1, a shared signaling partner of both the flagellin receptor FLS2 and the brassinosteroid receptor BRI1. This targeting interferes with ligand-dependent association of FLS2 with BAK1 during infection. It also impedes BAK1-dependent host immune responses to diverse other MAMPs and brassinosteroid signaling. Significantly, the structural basis of AvrPto-BAK1 interaction appears to be distinct from AvrPto-Pto association required for effector-triggered immunity. These findings uncover a unique strategy of bacterial pathogenesis where virulence effectors block signal transmission through a key common component of multiple MAMP-receptor complexes.

DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212.

PubMed

Kim, Ju Young; Duan, Xin; Liu, Cindy Y; Jang, Mi-Hyeon; Guo, Junjie U; Pow-anpongkul, Nattapol; Kang, Eunchai; Song, Hongjun; Ming, Guo-li

2009-09-24

Disrupted-in-schizophrenia 1 (DISC1), a susceptibility gene for major mental illnesses, regulates multiple aspects of embryonic and adult neurogenesis. Here, we show that DISC1 suppression in newborn neurons of the adult hippocampus leads to overactivated signaling of AKT, another schizophrenia susceptibility gene. Mechanistically, DISC1 directly interacts with KIAA1212, an AKT binding partner that enhances AKT signaling in the absence of DISC1, and DISC1 binding to KIAA1212 prevents AKT activation in vitro. Functionally, multiple genetic manipulations to enhance AKT signaling in adult-born neurons in vivo exhibit similar defects as DISC1 suppression in neuronal development that can be rescued by pharmacological inhibition of mammalian target of rapamycin (mTOR), an AKT downstream effector. Our study identifies the AKT-mTOR signaling pathway as a critical DISC1 target in regulating neuronal development and provides a framework for understanding how multiple susceptibility genes may functionally converge onto a common pathway in contributing to the etiology of certain psychiatric disorders.

Novel fMRI working memory paradigm accurately detects cognitive impairment in multiple sclerosis.

PubMed

Nelson, Flavia; Akhtar, Mohammad A; Zúñiga, Edward; Perez, Carlos A; Hasan, Khader M; Wilken, Jeffrey; Wolinsky, Jerry S; Narayana, Ponnada A; Steinberg, Joel L

2017-05-01

Cognitive impairment (CI) cannot be diagnosed by magnetic resonance imaging (MRI). Functional magnetic resonance imaging (fMRI) paradigms, such as the immediate/delayed memory task (I/DMT), detect varying degrees of working memory (WM). Preliminary findings using I/DMT showed differences in blood oxygenation level dependent (BOLD) activation between impaired (MSCI, n = 12) and non-impaired (MSNI, n = 9) multiple sclerosis (MS) patients. The aim of the study was to confirm CI detection based on I/DMT BOLD activation in a larger cohort of MS patients. The role of T2 lesion volume (LV) and Expanded Disability Status Scale (EDSS) in magnitude of BOLD signal was also sought. A total of 50 patients (EDSS mean ( m) = 3.2, disease duration (DD) m = 12 years, and age m = 40 years) underwent the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) and I/DMT. Working memory activation (WMa) represents BOLD signal during DMT minus signal during IMT. CI was based on MACFIMS. A total of 10 MSNI, 30 MSCI, and 4 borderline patients were included in the analyses. Analysis of variance (ANOVA) showed MSNI had significantly greater WMa than MSCI, in the left prefrontal cortex and left supplementary motor area ( p = 0.032). Regression analysis showed significant inverse correlations between WMa and T2 LV/EDSS in similar areas ( p = 0.005, 0.004, respectively). I/DMT-based BOLD activation detects CI in MS. Larger studies are needed to confirm these findings.

Multiplicative point process as a model of trading activity

NASA Astrophysics Data System (ADS)

Gontis, V.; Kaulakys, B.

2004-11-01

Signals consisting of a sequence of pulses show that inherent origin of the 1/ f noise is a Brownian fluctuation of the average interevent time between subsequent pulses of the pulse sequence. In this paper, we generalize the model of interevent time to reproduce a variety of self-affine time series exhibiting power spectral density S( f) scaling as a power of the frequency f. Furthermore, we analyze the relation between the power-law correlations and the origin of the power-law probability distribution of the signal intensity. We introduce a stochastic multiplicative model for the time intervals between point events and analyze the statistical properties of the signal analytically and numerically. Such model system exhibits power-law spectral density S( f)∼1/ fβ for various values of β, including β= {1}/{2}, 1 and {3}/{2}. Explicit expressions for the power spectra in the low-frequency limit and for the distribution density of the interevent time are obtained. The counting statistics of the events is analyzed analytically and numerically, as well. The specific interest of our analysis is related with the financial markets, where long-range correlations of price fluctuations largely depend on the number of transactions. We analyze the spectral density and counting statistics of the number of transactions. The model reproduces spectral properties of the real markets and explains the mechanism of power-law distribution of trading activity. The study provides evidence that the statistical properties of the financial markets are enclosed in the statistics of the time interval between trades. A multiplicative point process serves as a consistent model generating this statistics.

Analysis of DOK-6 function in downstream signaling of RET in human neuroblastoma cells.

PubMed

Kurotsuchi, Ai; Murakumo, Yoshiki; Jijiwa, Mayumi; Kurokawa, Kei; Itoh, Yasutomo; Kodama, Yoshinori; Kato, Takuya; Enomoto, Atsushi; Asai, Naoya; Terasaki, Hiroko; Takahashi, Masahide

2010-05-01

Point mutations and structural alterations of the RET tyrosine kinase gene cause multiple endocrine neoplasia type 2 (MEN 2) and papillary thyroid carcinoma, respectively. RET activation by glial cell line-derived neurotrophic factor (GDNF) is essential for the development of the enteric nervous system and the kidney. The signal through RET tyrosine kinase requires several adaptor proteins including the DOK (downstream of kinase) family of proteins. Of the seven members of the DOK protein family, DOK-1, -4, -5, and -6 have been reported to play roles in the GDNF-RET signaling pathway. Although DOK-6 has been shown to bind to RET and promote GDNF-induced neurite outgrowth in mouse Neuro2A cells, DOK-6 function in human cells remains unclear. In the present study, we investigated the role of DOK-6 in GDNF-RET signaling in human cells including neuroblastoma cells. DOK-6 was constitutively localized to the plasma membrane via its pleckstrin homology (PH) domain, and was phosphorylated following RET activation via a MEN2A mutation or GDNF stimulation. However, DOK-6 could not significantly affect downstream signaling and neurite outgrowth in human neuroblastoma cells. The binding affinity of the DOK-6 phosphotyrosine-binding (PTB) domain to RET was much lower than that of the DOK-1, DOK-4, and SHC PTB domains to RET. These findings indicate that DOK-6 is involved in RET signaling with less influence when compared with DOK-1, DOK-4, and SHC.

Maturation of a central brain flight circuit in Drosophila requires Fz2/Ca2+ signaling

PubMed Central

Agrawal, Tarjani; Hasan, Gaiti

2015-01-01

The final identity of a differentiated neuron is determined by multiple signaling events, including activity dependent calcium transients. Non-canonical Frizzled2 (Fz2) signaling generates calcium transients that determine neuronal polarity, neuronal migration, and synapse assembly in the developing vertebrate brain. Here, we demonstrate a requirement for Fz2/Ca2+ signaling in determining the final differentiated state of a set of central brain dopaminergic neurons in Drosophila, referred to as the protocerebral anterior medial (PAM) cluster. Knockdown or inhibition of Fz2/Ca2+ signaling during maturation of the flight circuit in pupae reduces Tyrosine Hydroxylase (TH) expression in the PAM neurons and affects maintenance of flight. Thus, we demonstrate that Fz2/Ca2+ transients during development serve as a pre-requisite for normal adult behavior. Our results support a neural mechanism where PAM neuron send projections to the α' and β' lobes of a higher brain centre, the mushroom body, and function in dopaminergic re-inforcement of flight. DOI: http://dx.doi.org/10.7554/eLife.07046.001 PMID:25955970

Vasopressin and the Regulation of Thirst.

PubMed

Bichet, Daniel G

2018-01-01

Recent experiments using optogenetic tools allow the identification and functional analysis of thirst neurons and vasopressin producing neurons. Two major advances provide a detailed anatomy of taste for water and arginine-vasopressin (AVP) release: (1) thirst and AVP release are regulated not only by the classical homeostatic, intero-sensory plasma osmolality negative feedback, but also by novel, extero-sensory, anticipatory signals. These anticipatory signals for thirst and vasopressin release converge on the same homeostatic neurons of circumventricular organs that monitor the composition of the blood; (2) acid-sensing taste receptor cells (which express polycystic kidney disease 2-like 1 protein) on the tongue that were previously suggested as the sour taste sensors also mediate taste responses to water. The tongue has a taste for water. The median preoptic nucleus (MnPO) of the hypothalamus could integrate multiple thirst-generating stimuli including cardiopulmonary signals, osmolality, angiotensin II, oropharyngeal and gastric signals, the latter possibly representing anticipatory signals. Dehydration is aversive and MnPO neuron activity is proportional to the intensity of this aversive state. © 2018 The Author(s) Published by S. Karger AG, Basel.

Model observer design for multi-signal detection in the presence of anatomical noise

NASA Astrophysics Data System (ADS)

Wen, Gezheng; Markey, Mia K.; Park, Subok

2017-02-01

As psychophysical studies are resource-intensive to conduct, model observers are commonly used to assess and optimize medical imaging quality. Model observers are typically designed to detect at most one signal. However, in clinical practice, there may be multiple abnormalities in a single image set (e.g. multifocal multicentric (MFMC) breast cancer), which can impact treatment planning. Prevalence of signals can be different across anatomical regions, and human observers do not know the number or location of signals a priori. As new imaging techniques have the potential to improve multiple-signal detection (e.g. digital breast tomosynthesis may be more effective for diagnosis of MFMC than mammography), image quality assessment approaches addressing such tasks are needed. In this study, we present a model observer to detect multiple signals in an image dataset. A novel implementation of partial least squares (PLS) was developed to estimate different sets of efficient channels directly from the images. The PLS channels are adaptive to the characteristics of signals and the background, and they capture the interactions among signal locations. Corresponding linear decision templates are employed to generate both image-level and location-specific scores on the presence of signals. Our results show that: (1) the model observer can achieve high performance with a reasonably small number of channels; (2) the model observer with PLS channels outperforms that with benchmark modified Laguerre-Gauss channels, especially when realistic signal shapes and complex background statistics are involved; (3) the tasks of clinical interest, and other constraints such as sample size would alter the optimal design of the model observer.

Modeling lidar waveforms with time-dependent stochastic radiative transfer theory for remote estimations of forest structure

NASA Astrophysics Data System (ADS)

Kotchenova, Svetlana Y.; Shabanov, Nikolay V.; Knyazikhin, Yuri; Davis, Anthony B.; Dubayah, Ralph; Myneni, Ranga B.

2003-08-01

Large footprint waveform-recording laser altimeters (lidars) have demonstrated a potential for accurate remote sensing of forest biomass and structure, important for regional and global climate studies. Currently, radiative transfer analyses of lidar data are based on the simplifying assumption that only single scattering contributes to the return signal, which may lead to errors in the modeling of the lower portions of recorded waveforms in the near-infrared spectrum. In this study we apply time-dependent stochastic radiative transfer (RT) theory to model the propagation of lidar pulses through forest canopies. A time-dependent stochastic RT equation is formulated and solved numerically. Such an approach describes multiple scattering events, allows for realistic representation of forest structure including foliage clumping and gaps, simulates off-nadir and multiangular observations, and has the potential to provide better approximations of return waveforms. The model was tested with field data from two conifer forest stands (southern old jack pine and southern old black spruce) in central Canada and two closed canopy deciduous forest stands (with overstory dominated by tulip poplar) in eastern Maryland. Model-simulated signals were compared with waveforms recorded by the Scanning Lidar Imager of Canopies by Echo Recovery (SLICER) over these regions. Model simulations show good agreement with SLICER signals having a slow decay of the waveform. The analysis of the effects of multiple scattering shows that multiply scattered photons magnify the amplitude of the reflected signal, especially that originating from the lower portions of the canopy.

Multiphoton fluorescence lifetime imaging of chemotherapy distribution in solid tumors

NASA Astrophysics Data System (ADS)

Carlson, Marjorie; Watson, Adrienne L.; Anderson, Leah; Largaespada, David A.; Provenzano, Paolo P.

2017-11-01

Doxorubicin is a commonly used chemotherapeutic employed to treat multiple human cancers, including numerous sarcomas and carcinomas. Furthermore, doxorubicin possesses strong fluorescent properties that make it an ideal reagent for modeling drug delivery by examining its distribution in cells and tissues. However, while doxorubicin fluorescence and lifetime have been imaged in live tissue, its behavior in archival samples that frequently result from drug and treatment studies in human and animal patients, and murine models of human cancer, has to date been largely unexplored. Here, we demonstrate imaging of doxorubicin intensity and lifetimes in archival formalin-fixed paraffin-embedded sections from mouse models of human cancer with multiphoton excitation and multiphoton fluorescence lifetime imaging microscopy (FLIM). Multiphoton excitation imaging reveals robust doxorubicin emission in tissue sections and captures spatial heterogeneity in cells and tissues. However, quantifying the amount of doxorubicin signal in distinct cell compartments, particularly the nucleus, often remains challenging due to strong signals in multiple compartments. The addition of FLIM analysis to display the spatial distribution of excited state lifetimes clearly distinguishes between signals in distinct compartments such as the cell nuclei versus cytoplasm and allows for quantification of doxorubicin signal in each compartment. Furthermore, we observed a shift in lifetime values in the nuclei of transformed cells versus nontransformed cells, suggesting a possible diagnostic role for doxorubicin lifetime imaging to distinguish normal versus transformed cells. Thus, data here demonstrate that multiphoton FLIM is a highly sensitive platform for imaging doxorubicin distribution in normal and diseased archival tissues.

Phyllanthus Suppresses Prostate Cancer Cell, PC-3, Proliferation and Induces Apoptosis through Multiple Signalling Pathways (MAPKs, PI3K/Akt, NFκB, and Hypoxia).

PubMed

Tang, Yin-Quan; Jaganath, Indubala; Manikam, Rishya; Sekaran, Shamala Devi

2013-01-01

Phyllanthus is a traditional medicinal plant that has been found to have antihepatitis, antibacterial, and anticancer properties. The present studies were to investigate the in vitro molecular mechanisms of anticancer effects of Phyllanthus (P. amarus, P. niruri, P. urinaria, and P. watsonii) plant extracts in human prostate adenocarcinoma. The cancer ten-pathway reporter array was performed and revealed that the expression of six pathway reporters were significantly decreased (Wnt, NFκB, Myc/Max, hypoxia, MAPK/ERK, and MAPK/JNK) in PC-3 cells after treatment with Phyllanthus extracts. Western blot was conducted and identified several signalling molecules that were affected in the signalling pathways including pan-Ras, c-Raf, RSK, Elk1, c-Jun, JNK1/2, p38 MAPK, c-myc, DSH, β-catenin, Akt, HIF-1α, GSK3β, NFκB p50 and p52, Bcl-2, Bax, and VEGF, in treated PC-3 cells. A proteomics-based approach, 2D gel electrophoresis, was performed, and mass spectrometry (MS/MS) results revealed that there were 72 differentially expressed proteins identified in treated PC-3 cells and were involved in tumour cell adhesion, apoptosis, glycogenesis and glycolysis, metastasis, angiogenesis, and protein synthesis and energy metabolism. Overall, these findings suggest that Phyllanthus can interfere with multiple signalling cascades involved in tumorigenesis and be used as a potential therapeutic candidate for treatment of cancer.

Novel, continuous monitoring of fine‐scale movement using fixed‐position radiotelemetry arrays and random forest location fingerprinting

USGS Publications Warehouse

Harbicht, Andrew B.; Castro-Santos, Theodore R.; Ardren, William R.; Gorsky, Dimitry; Fraser, Dylan

2017-01-01

Radio‐tag signals from fixed‐position antennas are most often used to indicate presence or absence of individuals, or to estimate individual activity levels from signal strength variation within an antenna's detection zone. The potential of such systems to provide more precise information on tag location and movement has not been explored in great detail in an ecological setting.By reversing the roles that transmitters and receivers play in localization methods common to the telecommunications industry, we present a new telemetric tool for accurately estimating the location of tagged individuals from received signal strength values. The methods used to characterize the study area in terms of received signal strength are described, as is the random forest model used for localization. The resulting method is then validated using test data before being applied to true data collected from tagged individuals in the study site.Application of the localization method to test data withheld from the learning dataset indicated a low average error over the entire study area (<1 m), whereas application of the localization method to real data produced highly probable results consistent with field observations.This telemetric approach provided detailed movement data for tagged fish along a single axis (a migratory path) and is particularly useful for monitoring passage along migratory routes. The new methods applied in this study can also be expanded to include multiple axes (x, y, z) and multiple environments (aquatic and terrestrial) for remotely monitoring wildlife movement.

Ultrasensitive Electrochemical Detection of Glycoprotein Based on Boronate Affinity Sandwich Assay and Signal Amplification with Functionalized SiO2@Au Nanocomposites.

PubMed

You, Min; Yang, Shuai; Tang, Wanxin; Zhang, Fan; He, Pin-Gang

2017-04-26

Herein we propose a multiple signal amplification strategy designed for ultrasensitive electrochemical detection of glycoproteins. This approach introduces a new type of boronate-affinity sandwich assay (BASA), which was fabricated by using gold nanoparticles combined with reduced graphene oxide (AuNPs-GO) to modify sensing surface for accelerating electron transfer, the composite of molecularly imprinted polymer (MIP) including 4-vinylphenylboronic acid (VPBA) for specific capturing glycoproteins, and SiO 2 nanoparticles carried gold nanoparticles (SiO 2 @Au) labeled with 6-ferrocenylhexanethiol (FcHT) and 4-mercaptophenylboronic acid (MPBA) (SiO 2 @Au/FcHT/MPBA) as tracing tag for binding glycoprotein and generating electrochemical signal. As a sandwich-type sensing, the SiO 2 @Au/FcHT/MPBA was captured by glycoprotein on the surface of imprinting film for further electrochemical detection in 0.1 M PBS (pH 7.4). Using horseradish peroxidase (HRP) as a model glycoprotein, the proposed approach exhibited a wide linear range from 1 pg/mL to 100 ng/mL, with a low detection limit of 0.57 pg/mL. To the best of our knowledge, this is first report of a multiple signal amplification approach based on boronate-affinity molecularly imprinted polymer and SiO 2 @Au/FcHT/MPBA, exhibiting greatly enhanced sensitivity for glycoprotein detection. Furthermore, the newly constructed BASA based glycoprotein sensor demonstrated HRP detection in real sample, such as human serum, suggesting its promising prospects in clinical diagnostics.

Passive Transport Disrupts Grid Signals in the Parahippocampal Cortex.

PubMed

Winter, Shawn S; Mehlman, Max L; Clark, Benjamin J; Taube, Jeffrey S

2015-10-05

Navigation is usually thought of relative to landmarks, but neural signals representing space also use information generated by an animal's movements. These signals include grid cells, which fire at multiple locations, forming a repeating grid pattern. Grid cell generation depends upon theta rhythm, a 6-10 Hz electroencephalogram (EEG) oscillation that is modulated by the animals' movement velocity. We passively moved rats in a clear cart to eliminate motor related self-movement cues that drive moment-to-moment changes in theta rhythmicity. We found that passive movement maintained theta power and frequency at levels equivalent to low active movement velocity, spared overall head-direction (HD) cell characteristics, but abolished both velocity modulation of theta rhythmicity and grid cell firing patterns. These results indicate that self-movement motor cues are necessary for generating grid-specific firing patterns, possibly by driving velocity modulation of theta rhythmicity, which may be used as a speed signal to generate the repeating pattern of grid cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

Generalized stochastic resonance for a fractional harmonic oscillator with bias-signal-modulated trichotomous noise

NASA Astrophysics Data System (ADS)

Lin, Lifeng; Wang, Huiqi; Huang, Xipei; Wen, Yongxian

2018-03-01

For a fractional linear oscillator subjected to both parametric excitation of trichotomous noise and external excitation of bias-signal-modulated trichotomous noise, the generalized stochastic resonance (GSR) phenomena are investigated in this paper in case the noises are cross-correlative. First, the generalized Shapiro-Loginov formula and generalized fractional Shapiro-Loginov formula are derived. Then, by using the generalized (fractional) Shapiro-Loginov formula and the Laplace transformation technique, the exact expression of the first-order moment of the system’s steady response is obtained. The numerical results show that the evolution of the output amplitude amplification is nonmonotonic with the frequency of periodic signal, the noise parameters, and the fractional order. The GSR phenomena, including single-peak GSR, double-peak GSR and triple-peak GSR, are observed in this system. In addition, the interplay of the multiplicative trichotomous noise, bias-signal-modulated trichotomous noise and memory can induce and diversify the stochastic multi-resonance (SMR) phenomena, and the two kinds of trichotomous noises play opposite roles on the GSR.

BMP Signaling in Astrocytes Downregulates EGFR to Modulate Survival and Maturation

PubMed Central

Scholze, Anja R.; Foo, Lynette C.; Mulinyawe, Sara; Barres, Ben A.

2014-01-01

Astrocytes constitute a major cell population in the brain with a myriad of essential functions, yet we know remarkably little about the signaling pathways and mechanisms that direct astrocyte maturation. To explore the signals regulating astrocyte development, we prospectively purified and cultured immature postnatal rodent astrocytes. We identified fibroblast growth factors (FGFs) and bone morphogenetic proteins (BMPs) as robust trophic factors for immature astrocytes. We showed that astrocytes respond directly to BMPs via phosphorylation of the smad1/5/8 pathway. In vitro, BMP signaling promoted immature astrocytes to adopt multiple characteristics of mature astrocytes, including a more process-bearing morphology, aquaporin-4 (AQP4) and S100β immunoreactivity, limited proliferation, and strong downregulation of epidermal growth factor receptor (EGFR). In vivo, activation of the smad1/5/8 pathway in astrocytes was seen during early postnatal development, but inhibition of astrocyte proliferation was not observed. These insights can aid in the further dissection of the mechanisms and pathways controlling astrocyte biology and development. PMID:25330173

Passive Transport Disrupts Grid Signals in the Parahippocampal Cortex

PubMed Central

Winter, Shawn S.; Mehlman, Max L.; Clark, Benjamin J.; Taube, Jeffrey S.

2015-01-01

Summary Navigation is usually thought of relative to landmarks, but neural signals representing space also use information generated by an animal’s movements. These signals include grid cells, which fire at multiple locations forming a repeating grid pattern. Grid cell generation depends upon theta rhythm, a 6-10 Hz EEG oscillation that is modulated by the animals’ movement velocity. We passively moved rats in a clear cart to eliminate motor related self-movement cues that drive moment-to-moment changes in theta rhythmicity. We found that passive movement maintained theta power and frequency at levels equivalent to low active movement velocity, spared overall HD cell characteristics, and abolished velocity modulation of theta rhythmicity and grid cell firing patterns. These results indicate that self-movement motor cues are necessary for generating grid-specific firing patterns, possibly by driving velocity modulation of theta rhythmicity. Velocity modulation of theta may be used as a speed signal to generate the repeating pattern of grid cells. PMID:26387719

Development of an EMCCD for LIDAR applications

NASA Astrophysics Data System (ADS)

De Monte, B.; Bell, R. T.

2017-11-01

A novel detector, incorporating e2v's EMCCD (L3VisionTM) [1] technology for use in LIDAR (Light Detection And Ranging) applications has been designed, manufactured and characterised. The most critical performance aspect was the requirement to collect charge from a 120μm square detection area for a 667ns temporal sampling window, with low crosstalk between successive samples, followed by signal readout with sub-electron effective noise. Additional requirements included low dark signal, high quantum efficiency at the 355nm laser wavelength and the ability to handle bright laser echoes, without corruption of the much fainter useful signals. The detector architecture used high speed charge binning to combine signal from each sampling window into a single charge packet. This was then passed through a multiplication register (EMCCD) operating with a typical gain of 100X to a conventional charge detection circuit. The detector achieved a typical quantum efficiency of 80% and a total noise in darkness of < 0.5 electrons rms. Development of the detector was supported by ESA.

Role of FGFs/FGFRs in skeletal development and bone regeneration.

PubMed

Du, Xiaolan; Xie, Yangli; Xian, Cory J; Chen, Lin

2012-12-01

Fibroblast growth factor (FGF)/FGF (FGFR) signaling is an important pathway involved in skeletal development. Missense mutations in FGFs and FGFRs were found clinically to cause multiple congenital skeleton diseases including chondrodysplasia, craniosynostosis, syndromes with dysregulated phosphate metabolism. FGFs/FGFRs also have crucial roles in bone fracture repair and bone regeneration. Understanding the molecular mechanisms for the role of FGFs/FGFRs in the regulation of skeletal development, genetic skeletal diseases, and fracture healing will ultimately lead to better treatment of skeleton diseases caused by mutations of FGFs/FGFRs and fracture. This review summarizes the major findings on the role of FGF signaling in skeletal development, genetic skeletal diseases and bone healing, and discusses issues that remain to be resolved in applying FGF signaling-related measures to promote bone healing. This review has also provided a perspective view on future work for exploring the roles and action mechanisms of FGF signaling in skeletal development, genetic skeletal diseases, and fracture healing. Copyright © 2012 Wiley Periodicals, Inc.

Two Strikes: American Intervention in Haiti

DTIC Science & Technology

2002-04-12

Richard Millet , “A Multiplicity of Threats, A Paucity of Options: The Global Security Environment at the End of the Twentieth Century” in Beyond Declaring...execute their campaign of pacification.27 Toussaint and his principle generals, including a rising and brutal leader Jean -Jacques Dessalines, reacted by...French and consigned to exile where he died.28 The death of Toussaint signaled the beginning of a new war, Jean -Jacques Dessalines succeeded Toussaint, as

Performance Comparison of Superresolution Array Processing Algorithms. Revised

DTIC Science & Technology

1998-06-15

plane waves is finite is the MUSIC algorithm [16]. MUSIC , which denotes Multiple Signal Classification, is an extension of the method of Pisarenko [18... MUSIC Is but one member of a class of methods based upon the decomposition of covariance data into eigenvectors and eigenvalues. Such techniques...techniques relative to the classical methods, however, results for MUSIC are included in this report. All of the techniques reviewed have application to

VHF Air/Ground Communications for Air Traffic Control: A Decision Tree Approach to System Innovations. Volume 2

DTIC Science & Technology

1993-07-01

GROUND RADIO ISSUES Multiple transmitters and receivers at a common site has been a dfficult integration issue for many communicaton systems...lower data rate vocoders become available. 10. Compatibility of modulation with channel availability and message integrity improvements, including...overrides can use in- frequency and path diversity, integrity improvements band signaling, busy channel overrides, and Frequency diversity and ARQ ARQ is

easyGWAS: A Cloud-Based Platform for Comparing the Results of Genome-Wide Association Studies.

PubMed

Grimm, Dominik G; Roqueiro, Damian; Salomé, Patrice A; Kleeberger, Stefan; Greshake, Bastian; Zhu, Wangsheng; Liu, Chang; Lippert, Christoph; Stegle, Oliver; Schölkopf, Bernhard; Weigel, Detlef; Borgwardt, Karsten M

2017-01-01

The ever-growing availability of high-quality genotypes for a multitude of species has enabled researchers to explore the underlying genetic architecture of complex phenotypes at an unprecedented level of detail using genome-wide association studies (GWAS). The systematic comparison of results obtained from GWAS of different traits opens up new possibilities, including the analysis of pleiotropic effects. Other advantages that result from the integration of multiple GWAS are the ability to replicate GWAS signals and to increase statistical power to detect such signals through meta-analyses. In order to facilitate the simple comparison of GWAS results, we present easyGWAS, a powerful, species-independent online resource for computing, storing, sharing, annotating, and comparing GWAS. The easyGWAS tool supports multiple species, the uploading of private genotype data and summary statistics of existing GWAS, as well as advanced methods for comparing GWAS results across different experiments and data sets in an interactive and user-friendly interface. easyGWAS is also a public data repository for GWAS data and summary statistics and already includes published data and results from several major GWAS. We demonstrate the potential of easyGWAS with a case study of the model organism Arabidopsis thaliana , using flowering and growth-related traits. © 2016 American Society of Plant Biologists. All rights reserved.

Multiple Trellis Coded Modulation (MTCM): An MSAT-X report

NASA Technical Reports Server (NTRS)

Divsalar, D.; Simon, M. K.

1986-01-01

Conventional trellis coding outputs one channel symbol per trellis branch. The notion of multiple trellis coding is introduced wherein more than one channel symbol per trellis branch is transmitted. It is shown that the combination of multiple trellis coding with M-ary modulation yields a performance gain with symmetric signal set comparable to that previously achieved only with signal constellation asymmetry. The advantage of multiple trellis coding over the conventional trellis coded asymmetric modulation technique is that the potential for code catastrophe associated with the latter has been eliminated with no additional cost in complexity (as measured by the number of states in the trellis diagram).

A transcriptomic study reveals differentially expressed genes and pathways respond to simulated acid rain in Arabidopsis thaliana.

PubMed

Liu, Ting-Wu; Niu, Li; Fu, Bin; Chen, Juan; Wu, Fei-Hua; Chen, Juan; Wang, Wen-Hua; Hu, Wen-Jun; He, Jun-Xian; Zheng, Hai-Lei

2013-01-01

Acid rain, as a worldwide environmental issue, can cause serious damage to plants. In this study, we provided the first case study on the systematic responses of arabidopsis (Arabidopsis thaliana (L.) Heynh.) to simulated acid rain (SiAR) by transcriptome approach. Transcriptomic analysis revealed that the expression of a set of genes related to primary metabolisms, including nitrogen, sulfur, amino acid, photosynthesis, and reactive oxygen species metabolism, were altered under SiAR. In addition, transport and signal transduction related pathways, especially calcium-related signaling pathways, were found to play important roles in the response of arabidopsis to SiAR stress. Further, we compared our data set with previously published data sets on arabidopsis transcriptome subjected to various stresses, including wound, salt, light, heavy metal, karrikin, temperature, osmosis, etc. The results showed that many genes were overlapped in several stresses, suggesting that plant response to SiAR is a complex process, which may require the participation of multiple defense-signaling pathways. The results of this study will help us gain further insights into the response mechanisms of plants to acid rain stress.

The control of translational accuracy is a determinant of healthy ageing in yeast

PubMed Central

Leadsham, Jane E.; Sauvadet, Aimie; Tarrant, Daniel; Adam, Ilectra S.; Saromi, Kofo; Laun, Peter; Rinnerthaler, Mark; Breitenbach-Koller, Hannelore; Breitenbach, Michael; Tuite, Mick F.; Gourlay, Campbell W.

2017-01-01

Life requires the maintenance of molecular function in the face of stochastic processes that tend to adversely affect macromolecular integrity. This is particularly relevant during ageing, as many cellular functions decline with age, including growth, mitochondrial function and energy metabolism. Protein synthesis must deliver functional proteins at all times, implying that the effects of protein synthesis errors like amino acid misincorporation and stop-codon read-through must be minimized during ageing. Here we show that loss of translational accuracy accelerates the loss of viability in stationary phase yeast. Since reduced translational accuracy also reduces the folding competence of at least some proteins, we hypothesize that negative interactions between translational errors and age-related protein damage together overwhelm the cellular chaperone network. We further show that multiple cellular signalling networks control basal error rates in yeast cells, including a ROS signal controlled by mitochondrial activity, and the Ras pathway. Together, our findings indicate that signalling pathways regulating growth, protein homeostasis and energy metabolism may jointly safeguard accurate protein synthesis during healthy ageing. PMID:28100667

The control of translational accuracy is a determinant of healthy ageing in yeast.

PubMed

von der Haar, Tobias; Leadsham, Jane E; Sauvadet, Aimie; Tarrant, Daniel; Adam, Ilectra S; Saromi, Kofo; Laun, Peter; Rinnerthaler, Mark; Breitenbach-Koller, Hannelore; Breitenbach, Michael; Tuite, Mick F; Gourlay, Campbell W

2017-01-01

Life requires the maintenance of molecular function in the face of stochastic processes that tend to adversely affect macromolecular integrity. This is particularly relevant during ageing, as many cellular functions decline with age, including growth, mitochondrial function and energy metabolism. Protein synthesis must deliver functional proteins at all times, implying that the effects of protein synthesis errors like amino acid misincorporation and stop-codon read-through must be minimized during ageing. Here we show that loss of translational accuracy accelerates the loss of viability in stationary phase yeast. Since reduced translational accuracy also reduces the folding competence of at least some proteins, we hypothesize that negative interactions between translational errors and age-related protein damage together overwhelm the cellular chaperone network. We further show that multiple cellular signalling networks control basal error rates in yeast cells, including a ROS signal controlled by mitochondrial activity, and the Ras pathway. Together, our findings indicate that signalling pathways regulating growth, protein homeostasis and energy metabolism may jointly safeguard accurate protein synthesis during healthy ageing. © 2017 The Authors.

MicroRNA-214 controls skin and hair follicle development by modulating the activity of the Wnt pathway

PubMed Central

Ahmed, Mohammed I.; Alam, Majid; Emelianov, Vladimir U.; Poterlowicz, Krzysztof; Patel, Ankit; Sharov, Andrey A.; Mardaryev, Andrei N.

2014-01-01

Skin development is governed by complex programs of gene activation and silencing, including microRNA-dependent modulation of gene expression. Here, we show that miR-214 regulates skin morphogenesis and hair follicle (HF) cycling by targeting β-catenin, a key component of the Wnt signaling pathway. miR-214 exhibits differential expression patterns in the skin epithelium, and its inducible overexpression in keratinocytes inhibited proliferation, which resulted in formation of fewer HFs with decreased hair bulb size and thinner hair production. The inhibitory effects of miR-214 on HF development and cycling were associated with altered activities of multiple signaling pathways, including decreased expression of key Wnt signaling mediators β-catenin and Lef-1, and were rescued by treatment with pharmacological Wnt activators. Finally, we identify β-catenin as one of the conserved miR-214 targets in keratinocytes. These data provide an important foundation for further analyses of miR-214 as a key regulator of Wnt pathway activity and stem cell functions during normal tissue homeostasis, regeneration, and aging. PMID:25422376

Insights into the Shc Family of Adaptor Proteins

PubMed Central

Prigent, Sally A.

2017-01-01

The Shc family of adaptor proteins is a group of proteins that lacks intrinsic enzymatic activity. Instead, Shc proteins possess various domains that allow them to recruit different signalling molecules. Shc proteins help to transduce an extracellular signal into an intracellular signal, which is then translated into a biological response. The Shc family of adaptor proteins share the same structural topography, CH2-PTB-CH1-SH2, which is more than an isoform of Shc family proteins; this structure, which includes multiple domains, allows for the posttranslational modification of Shc proteins and increases the functional diversity of Shc proteins. The deregulation of Shc proteins has been linked to different disease conditions, including cancer and Alzheimer’s, which indicates their key roles in cellular functions. Accordingly, a question might arise as to whether Shc proteins could be targeted therapeutically to correct their disturbance. To answer this question, thorough knowledge must be acquired; herein, we aim to shed light on the Shc family of adaptor proteins to understand their intracellular role in normal and disease states, which later might be applied to connote mechanisms to reverse the disease state.

High resolution crustal image of South California Continental Borderland: Reverse time imaging including multiples

NASA Astrophysics Data System (ADS)

Bian, A.; Gantela, C.

2014-12-01

Strong multiples were observed in marine seismic data of Los Angeles Regional Seismic Experiment (LARSE).It is crucial to eliminate these multiples in conventional ray-based or one-way wave-equation based depth image methods. As long as multiples contain information of target zone along travelling path, it's possible to use them as signal, to improve the illumination coverage thus enhance the image quality of structural boundaries. Reverse time migration including multiples is a two-way wave-equation based prestack depth image method that uses both primaries and multiples to map structural boundaries. Several factors, including source wavelet, velocity model, back ground noise, data acquisition geometry and preprocessing workflow may influence the quality of image. The source wavelet is estimated from direct arrival of marine seismic data. Migration velocity model is derived from integrated model building workflow, and the sharp velocity interfaces near sea bottom needs to be preserved in order to generate multiples in the forward and backward propagation steps. The strong amplitude, low frequency marine back ground noise needs to be removed before the final imaging process. High resolution reverse time image sections of LARSE Lines 1 and Line 2 show five interfaces: depth of sea-bottom, base of sedimentary basins, top of Catalina Schist, a deep layer and a possible pluton boundary. Catalina Schist shows highs in the San Clemente ridge, Emery Knoll, Catalina Ridge, under Catalina Basin on both the lines, and a minor high under Avalon Knoll. The high of anticlinal fold in Line 1 is under the north edge of Emery Knoll and under the San Clemente fault zone. An area devoid of any reflection features are interpreted as sides of an igneous plume.

The role of mTOR signalling in neurogenesis, insights from tuberous sclerosis complex.

PubMed

Tee, Andrew R; Sampson, Julian R; Pal, Deb K; Bateman, Joseph M

2016-04-01

Understanding the development and function of the nervous system is one of the foremost aims of current biomedical research. The nervous system is generated during a relatively short period of intense neurogenesis that is orchestrated by a number of key molecular signalling pathways. Even subtle defects in the activity of these molecules can have serious repercussions resulting in neurological, neurodevelopmental and neurocognitive problems including epilepsy, intellectual disability and autism. Tuberous sclerosis complex (TSC) is a monogenic disease characterised by these problems and by the formation of benign tumours in multiple organs, including the brain. TSC is caused by mutations in the TSC1 or TSC2 gene leading to activation of the mechanistic target of rapamycin (mTOR) signalling pathway. A desire to understand the neurological manifestations of TSC has stimulated research into the role of the mTOR pathway in neurogenesis. In this review we describe TSC neurobiology and how the use of animal model systems has provided insights into the roles of mTOR signalling in neuronal differentiation and migration. Recent progress in this field has identified novel mTOR pathway components regulating neuronal differentiation. The roles of mTOR signalling and aberrant neurogenesis in epilepsy are also discussed. Continuing efforts to understand mTOR neurobiology will help to identify new therapeutic targets for TSC and other neurological diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Phosphoinositide signaling in sperm development.

PubMed

Brill, Julie A; Yildirim, Sukriye; Fabian, Lacramioara

2016-11-01

Phosphatidylinositol phosphates (PIPs) 1 are membrane lipids with crucial roles during cell morphogenesis, including the establishment of cytoskeletal organization, membrane trafficking, cell polarity, cell-cycle control and signaling. Recent studies in mice (Mus musculus), fruit flies (Drosophila melanogaster) and other organisms have defined germ cell intrinsic requirements for these lipids and their regulatory enzymes in multiple aspects of sperm development. In particular, PIP levels are crucial in germline stem cell maintenance, spermatogonial proliferation and survival, spermatocyte cytokinesis, spermatid polarization, sperm tail formation, nuclear shaping, and production of mature, motile sperm. Here, we briefly review the stages of spermatogenesis and discuss the roles of PIPs and their regulatory enzymes in male germ cell development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Parallel Processing Strategies of the Primate Visual System

PubMed Central

Nassi, Jonathan J.; Callaway, Edward M.

2009-01-01

Preface Incoming sensory information is sent to the brain along modality-specific channels corresponding to the five senses. Each of these channels further parses the incoming signals into parallel streams to provide a compact, efficient input to the brain. Ultimately, these parallel input signals must be elaborated upon and integrated within the cortex to provide a unified and coherent percept. Recent studies in the primate visual cortex have greatly contributed to our understanding of how this goal is accomplished. Multiple strategies including retinal tiling, hierarchical and parallel processing and modularity, defined spatially and by cell type-specific connectivity, are all used by the visual system to recover the rich detail of our visual surroundings. PMID:19352403