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Sample records for dynamic signal analyses

  1. Dynamic reorganization of the AC16 cardiomyocyte transcriptome in response to TNFα signaling revealed by integrated genomic analyses

    PubMed Central

    2014-01-01

    Background Defining cell type-specific transcriptomes in mammals can be challenging, especially for unannotated regions of the genome. We have developed an analytical pipeline called groHMM for annotating primary transcripts using global nuclear run-on sequencing (GRO-seq) data. Herein, we use this pipeline to characterize the transcriptome of an immortalized adult human ventricular cardiomyocyte cell line (AC16) in response to signaling by tumor necrosis factor alpha (TNFα), which is controlled in part by NF-κB, a key transcriptional regulator of inflammation. A unique aspect of this work is the use of the RNA polymerase II (Pol II) inhibitor α-amanitin, which we used to define a set of RNA polymerase I and III (Pol I and Pol III) transcripts. Results Using groHMM, we identified ~30,000 coding and non-coding transcribed regions in AC16 cells, which includes a set of unique Pol I and Pol III primary transcripts. Many of these transcripts have not been annotated previously, including enhancer RNAs originating from NF-κB binding sites. In addition, we observed that AC16 cells rapidly and dynamically reorganize their transcriptomes in response to TNFα stimulation in an NF-κB-dependent manner, switching from a basal state to a proinflammatory state affecting a spectrum of cardiac-associated protein-coding and non-coding genes. Moreover, we observed distinct Pol II dynamics for up- and downregulated genes, with a rapid release of Pol II into productive elongation for TNFα-stimulated genes. As expected, the TNFα-induced changes in the AC16 transcriptome resulted in corresponding changes in cognate mRNA and protein levels in a similar manner, but with delayed kinetics. Conclusions Our studies illustrate how computational genomics can be used to characterize the signal-regulated transcriptome in biologically relevant cell types, providing new information about how the human genome is organized, transcribed and regulated. In addition, they show how α-amanitin can

  2. Sending Signals Dynamically

    PubMed Central

    Smock, Robert G.; Gierasch, Lila M.

    2010-01-01

    Proteins mediate transmission of signals along intercellular and intracellular pathways and between the exterior and the interior of a cell. The dynamic properties of signaling proteins are crucial to their functions. We discuss emerging paradigms for the role of protein dynamics in signaling. A central tenet is that proteins fluctuate among many states on evolutionarily selected energy landscapes. Upstream signals remodel this landscape, causing signaling proteins to transmit information to downstream partners. New methods provide insight into the dynamic properties of signaling proteins at the atomic scale. The next stages in the signaling hierarchy—how multiple signals are integrated and how cellular signaling pathways are organized in space and time—present exciting challenges for the future, requiring bold multidisciplinary approaches. PMID:19359576

  3. Mutational analyses of HAMP helices suggest a dynamic bundle model of input-output signalling in chemoreceptors.

    PubMed

    Zhou, Qin; Ames, Peter; Parkinson, John S

    2009-09-01

    To test the gearbox model of HAMP signalling in the Escherichia coli serine receptor, Tsr, we generated a series of amino acid replacements at each residue of the AS1 and AS2 helices. The residues most critical for Tsr function defined hydrophobic packing faces consistent with a four-helix bundle. Suppression patterns of helix lesions conformed to the predicted packing layers in the bundle. Although the properties and patterns of most AS1 and AS2 lesions were consistent with both proposed gearbox structures, some mutational features specifically indicate the functional importance of an x-da bundle over an alternative a-d bundle. These genetic data suggest that HAMP signalling could simply involve changes in the stability of its x-da bundle. We propose that Tsr HAMP controls output signals by modulating destabilizing phase clashes between the AS2 helices and the adjoining kinase control helices. Our model further proposes that chemoeffectors regulate HAMP bundle stability through a control cable connection between the transmembrane segments and AS1 helices. Attractant stimuli, which cause inward piston displacements in chemoreceptors, should reduce cable tension, thereby stabilizing the HAMP bundle. This study shows how transmembrane signalling and HAMP input-output control could occur without the helix rotations central to the gearbox model. PMID:19656294

  4. Some dynamics of signaling games

    PubMed Central

    Huttegger, Simon; Skyrms, Brian; Tarrès, Pierre; Wagner, Elliott

    2014-01-01

    Information transfer is a basic feature of life that includes signaling within and between organisms. Owing to its interactive nature, signaling can be investigated by using game theory. Game theoretic models of signaling have a long tradition in biology, economics, and philosophy. For a long time the analyses of these games has mostly relied on using static equilibrium concepts such as Pareto optimal Nash equilibria or evolutionarily stable strategies. More recently signaling games of various types have been investigated with the help of game dynamics, which includes dynamical models of evolution and individual learning. A dynamical analysis leads to more nuanced conclusions as to the outcomes of signaling interactions. Here we explore different kinds of signaling games that range from interactions without conflicts of interest between the players to interactions where their interests are seriously misaligned. We consider these games within the context of evolutionary dynamics (both infinite and finite population models) and learning dynamics (reinforcement learning). Some results are specific features of a particular dynamical model, whereas others turn out to be quite robust across different models. This suggests that there are certain qualitative aspects that are common to many real-world signaling interactions. PMID:25024209

  5. Some dynamics of signaling games.

    PubMed

    Huttegger, Simon; Skyrms, Brian; Tarrès, Pierre; Wagner, Elliott

    2014-07-22

    Information transfer is a basic feature of life that includes signaling within and between organisms. Owing to its interactive nature, signaling can be investigated by using game theory. Game theoretic models of signaling have a long tradition in biology, economics, and philosophy. For a long time the analyses of these games has mostly relied on using static equilibrium concepts such as Pareto optimal Nash equilibria or evolutionarily stable strategies. More recently signaling games of various types have been investigated with the help of game dynamics, which includes dynamical models of evolution and individual learning. A dynamical analysis leads to more nuanced conclusions as to the outcomes of signaling interactions. Here we explore different kinds of signaling games that range from interactions without conflicts of interest between the players to interactions where their interests are seriously misaligned. We consider these games within the context of evolutionary dynamics (both infinite and finite population models) and learning dynamics (reinforcement learning). Some results are specific features of a particular dynamical model, whereas others turn out to be quite robust across different models. This suggests that there are certain qualitative aspects that are common to many real-world signaling interactions. PMID:25024209

  6. Inelastic and Dynamic Fracture and Stress Analyses

    NASA Technical Reports Server (NTRS)

    Atluri, S. N.

    1984-01-01

    Large deformation inelastic stress analysis and inelastic and dynamic crack propagation research work is summarized. The salient topics of interest in engine structure analysis that are discussed herein include: (1) a path-independent integral (T) in inelastic fracture mechanics, (2) analysis of dynamic crack propagation, (3) generalization of constitutive relations of inelasticity for finite deformations , (4) complementary energy approaches in inelastic analyses, and (5) objectivity of time integration schemes in inelastic stress analysis.

  7. Phosphoproteomic Analyses Reveal Signaling Pathways That Facilitate Lytic Gammaherpesvirus Replication

    PubMed Central

    Stahl, James A.; Chavan, Shweta S.; Sifford, Jeffrey M.; MacLeod, Veronica; Voth, Daniel E.; Edmondson, Ricky D.; Forrest, J. Craig

    2013-01-01

    Lytic gammaherpesvirus (GHV) replication facilitates the establishment of lifelong latent infection, which places the infected host at risk for numerous cancers. As obligate intracellular parasites, GHVs must control and usurp cellular signaling pathways in order to successfully replicate, disseminate to stable latency reservoirs in the host, and prevent immune-mediated clearance. To facilitate a systems-level understanding of phosphorylation-dependent signaling events directed by GHVs during lytic replication, we utilized label-free quantitative mass spectrometry to interrogate the lytic replication cycle of murine gammaherpesvirus-68 (MHV68). Compared to controls, MHV68 infection regulated by 2-fold or greater ca. 86% of identified phosphopeptides – a regulatory scale not previously observed in phosphoproteomic evaluations of discrete signal-inducing stimuli. Network analyses demonstrated that the infection-associated induction or repression of specific cellular proteins globally altered the flow of information through the host phosphoprotein network, yielding major changes to functional protein clusters and ontologically associated proteins. A series of orthogonal bioinformatics analyses revealed that MAPK and CDK-related signaling events were overrepresented in the infection-associated phosphoproteome and identified 155 host proteins, such as the transcription factor c-Jun, as putative downstream targets. Importantly, functional tests of bioinformatics-based predictions confirmed ERK1/2 and CDK1/2 as kinases that facilitate MHV68 replication and also demonstrated the importance of c-Jun. Finally, a transposon-mutant virus screen identified the MHV68 cyclin D ortholog as a viral protein that contributes to the prominent MAPK/CDK signature of the infection-associated phosphoproteome. Together, these analyses enhance an understanding of how GHVs reorganize and usurp intracellular signaling networks to facilitate infection and replication. PMID:24068923

  8. Static and dynamic analyses of tensegrity structures

    NASA Astrophysics Data System (ADS)

    Nishimura, Yoshitaka

    Tensegrity structures are a class of truss structures consisting of a continuous set of tension members (cables) and a discrete set of compression members (bars). Since tensegrity structures are light weight and can be compactly stowed and deployed, cylindrical tensegrity modules have been proposed for space structures. From a view point of structural dynamics, tensegrity structures pose a new set of problems, i.e., initial shape finding. Initial configurations of tensegrity structures must be computed by imposing a pre-stressability condition to initial equilibrium equations. There are ample qualitative statements regarding the initial geometry of cylindrical and spherical tensegrity modules. Quantitative initial shape anlyses have only been performed on one-stage and two-stage cylindrical modules. However, analytical expressions for important geometrical parameters such as twist angles and overlap ratios lack the definition of the initial shape of both cylindrical and spherical tensegrity modules. In response to the above needs, a set of static and dynamic characterization procedures for tensegrity modules was first developed. The procedures were subsequently applied to Buckminster Fuller's spherical tensegrity modules. Both the initial shape and the corresponding pre-stress mode were analytically obtained by using the graphs of the tetrahedral, octahedral (cubic), and icosahedral (dodecahedral) groups. For pre-stressed configurations, modal analyses were conducted to classify a large number of infinitesimal mechanism modes. The procedures also applied tocyclic cylindrical tensegrity modules with an arbitrary number of stages. It was found that both the Maxwell number and the number of infinitesimal mechanism modes are independent of the number of stages in the axial direction. A reduced set of equilibrium equations was derived by incorporating cyclic symmetry and the flip, or quasi-flip, symmetry of the cylindrical modules. For multi-stage modules with more than

  9. Dynamic range control of audio signals by digital signal processing

    NASA Astrophysics Data System (ADS)

    Gilchrist, N. H. C.

    It is often necessary to reduce the dynamic range of musical programs, particularly those comprising orchestral and choral music, for them to be received satisfactorily by listeners to conventional FM and AM broadcasts. With the arrival of DAB (Digital Audio Broadcasting) a much wider dynamic range will become available for radio broadcasting, although some listeners may prefer to have a signal with a reduced dynamic range. This report describes a digital processor developed by the BBC to control the dynamic range of musical programs in a manner similar to that of a trained Studio Manager. It may be used prior to transmission in conventional broadcasting, replacing limiters or other compression equipment. In DAB, it offers the possibility of providing a dynamic range control signal to be sent to the receiver via an ancillary data channel, simultaneously with the uncompressed audio, giving the listener the option of the full dynamic range or a reduced dynamic range.

  10. Comparative analyses of lysophosphatidic acid receptor-mediated signaling.

    PubMed

    Fukushima, Nobuyuki; Ishii, Shoichi; Tsujiuchi, Toshifumi; Kagawa, Nao; Katoh, Kazutaka

    2015-06-01

    Lysophosphatidic acid (LPA) is a bioactive lipid mediator that activates G protein-coupled LPA receptors to exert fundamental cellular functions. Six LPA receptor genes have been identified in vertebrates and are classified into two subfamilies, the endothelial differentiation genes (edg) and the non-edg family. Studies using genetically engineered mice, frogs, and zebrafish have demonstrated that LPA receptor-mediated signaling has biological, developmental, and pathophysiological functions. Computational analyses have also identified several amino acids (aa) critical for LPA recognition by human LPA receptors. This review focuses on the evolutionary aspects of LPA receptor-mediated signaling by comparing the aa sequences of vertebrate LPA receptors and LPA-producing enzymes; it also summarizes the LPA receptor-dependent effects commonly observed in mouse, frog, and fish. PMID:25732591

  11. Structural dynamics analyses testing and correlation

    NASA Technical Reports Server (NTRS)

    Caughey, T. K.

    1982-01-01

    Some aspects of the lack of close correlation between the predictions of analytical modeling of dynamic structures and the results of vibration tests on such structures are examined. Ways in which the correlation may be improved are suggested.

  12. Network Features and Pathway Analyses of a Signal Transduction Cascade

    PubMed Central

    Yanashima, Ryoji; Kitagawa, Noriyuki; Matsubara, Yoshiya; Weatheritt, Robert; Oka, Kotaro; Kikuchi, Shinichi; Tomita, Masaru; Ishizaki, Shun

    2008-01-01

    The scale-free and small-world network models reflect the functional units of networks. However, when we investigated the network properties of a signaling pathway using these models, no significant differences were found between the original undirected graphs and the graphs in which inactive proteins were eliminated from the gene expression data. We analyzed signaling networks by focusing on those pathways that best reflected cellular function. Therefore, our analysis of pathways started from the ligands and progressed to transcription factors and cytoskeletal proteins. We employed the Python module to assess the target network. This involved comparing the original and restricted signaling cascades as a directed graph using microarray gene expression profiles of late onset Alzheimer's disease. The most commonly used method of shortest-path analysis neglects to consider the influences of alternative pathways that can affect the activation of transcription factors or cytoskeletal proteins. We therefore introduced included k-shortest paths and k-cycles in our network analysis using the Python modules, which allowed us to attain a reasonable computational time and identify k-shortest paths. This technique reflected results found in vivo and identified pathways not found when shortest path or degree analysis was applied. Our module enabled us to comprehensively analyse the characteristics of biomolecular networks and also enabled analysis of the effects of diseases considering the feedback loop and feedforward loop control structures as an alternative path. PMID:19543432

  13. Analyses and Measures of GPR Signal with Superimposed Noise

    NASA Astrophysics Data System (ADS)

    Chicarella, Simone; Ferrara, Vincenzo; D'Atanasio, Paolo; Frezza, Fabrizio; Pajewski, Lara; Pavoncello, Settimio; Prontera, Santo; Tedeschi, Nicola; Zambotti, Alessandro

    2014-05-01

    The influence of EM noises and environmental hard conditions on the GPR surveys has been examined analytically [1]. In the case of pulse radar GPR, many unwanted signals as stationary clutter, non-stationary clutter, random noise, and time jitter, influence the measurement signal. When GPR is motionless, stationary clutter is the most dominant signal component due to the reflections of static objects different from the investigated target, and to the direct antenna coupling. Moving objects like e.g. persons and vehicles, and the swaying of tree crown, produce non-stationary clutter. Device internal noise and narrowband jamming are e.g. two potential sources of random noises. Finally, trigger instabilities generate random jitter. In order to estimate the effective influence of these noise signal components, we organized some experimental setup of measurement. At first, we evaluated for the case of a GPR basic detection, simpler image processing of radargram. In the future, we foresee experimental measurements for detection of the Doppler frequency changes induced by movements of targets (like physiological movements of survivors under debris). We obtain image processing of radargram by using of GSSI SIR® 2000 GPR system together with the UWB UHF GPR-antenna (SUB-ECHO HBD 300, a model manufactured by Radarteam company). Our work includes both characterization of GPR signal without (or almost without) a superimposed noise, and the effect of jamming originated from the coexistence of a different radio signal. For characterizing GPR signal, we organized a measurement setup that includes the following instruments: mod. FSP 30 spectrum analyser by Rohde & Schwarz which operates in the frequency range 9 KHz - 30 GHz, mod. Sucoflex 104 cable by Huber Suhner (10 MHz - 18 GHz), and HL050 antenna by Rohde & Schwarz (bandwidth: from 850 MHz to 26.5 GHz). The next analysis of superimposed jamming will examine two different signal sources: by a cellular phone and by a

  14. Signal prediction by anticipatory relaxation dynamics

    NASA Astrophysics Data System (ADS)

    Voss, Henning U.

    2016-03-01

    Real-time prediction of signals is a task often encountered in control problems as well as by living systems. Here, a parsimonious prediction approach based on the coupling of a linear relaxation-delay system to a smooth, stationary signal is described. The resulting anticipatory relaxation dynamics (ARD) is a frequency-dependent predictor of future signal values. ARD not only approximately predicts signals on average but can anticipate the occurrence of signal peaks, too. This can be explained by recognizing ARD as an input-output system with negative group delay. It is characterized, including its prediction horizon, by its analytically given frequency response function.

  15. Options for dynamic analyses of underground facilities

    SciTech Connect

    Chowdhury, A.H.; Hsiung, Suimin; Ahola, M.P.

    1993-09-01

    Continuum and discontinuum modeling techniques for conducting dynamic analysis of underground facilities of geologic repository are discussed. Compared with continuum analysis, the discontinuum analysis is relatively new and is most applicable to problems in which the deformation of the system is primarily a result of deformation or slip along the discontinuities.

  16. Signal phase switches offer greater dynamic range

    NASA Technical Reports Server (NTRS)

    Crow, R. B.

    1970-01-01

    Circuit, placed in the signal path of a closed-loop receiver to modulate telemetered data in the 10-MHz spectrum, improves signal-to-noise ratio by 3 db in a communication receiver. The switch enables bandwidth reduction which reduces noise overload on the following stages, giving the system greater dynamic range.

  17. Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility.

    PubMed

    Piccolo, Stephen R; Hoffman, Laura M; Conner, Thomas; Shrestha, Gajendra; Cohen, Adam L; Marks, Jeffrey R; Neumayer, Leigh A; Agarwal, Cori A; Beckerle, Mary C; Andrulis, Irene L; Spira, Avrum E; Moos, Philip J; Buys, Saundra S; Johnson, William Evan; Bild, Andrea H

    2016-03-01

    The signaling events that drive familial breast cancer (FBC) risk remain poorly understood. While the majority of genomic studies have focused on genetic risk variants, known risk variants account for at most 30% of FBC cases. Considering that multiple genes may influence FBC risk, we hypothesized that a pathway-based strategy examining different data types from multiple tissues could elucidate the biological basis for FBC. In this study, we performed integrated analyses of gene expression and exome-sequencing data from peripheral blood mononuclear cells and showed that cell adhesion pathways are significantly and consistently dysregulated in women who develop FBC. The dysregulation of cell adhesion pathways in high-risk women was also identified by pathway-based profiling applied to normal breast tissue data from two independent cohorts. The results of our genomic analyses were validated in normal primary mammary epithelial cells from high-risk and control women, using cell-based functional assays, drug-response assays, fluorescence microscopy, and Western blotting assays. Both genomic and cell-based experiments indicate that cell-cell and cell-extracellular matrix adhesion processes seem to be disrupted in non-malignant cells of women at high risk for FBC and suggest a potential role for these processes in FBC development. PMID:26969729

  18. Multifractal analyses of row sum signals of elementary cellular automata

    NASA Astrophysics Data System (ADS)

    Murguía, J. S.; Rosu, H. C.

    2012-07-01

    We first apply the WT-MFDFA, MFDFA, and WTMM multifractal methods to binomial multifractal time series of three different binomial parameters and find that the WTMM method indicates an enhanced difference between the fractal components than the known theoretical result. Next, we make use of the same methods for the time series of the row sum signals of the two complementary ECA pairs of rules (90,165) and (150,105) for ten initial conditions going from a single 1 in the central position up to a set of ten 1's covering the ten central positions in the first row. Since the members of the pairs are actually similar from the statistical point of view, we can check which method is the most stable numerically by recording the differences provided by the methods between the two members of the pairs for various important quantities of the scaling analyses, such as the multifractal support, the most frequent Hölder exponent, and the Hurst exponent and considering as the better one the method that provides the minimum differences. According to this criterion, our results show that the MFDFA performs better than WT-MFDFA and WTMM in the case of the multifractal support, while for the other two scaling parameters the WT-MFDFA is the best. The employed set of initial conditions does not generate any specific trend in the values of the multifractal parameters.

  19. Dynamic Redox Regulation of IL-4 Signaling

    PubMed Central

    Dwivedi, Gaurav; Gran, Margaret A.; Bagchi, Pritha; Kemp, Melissa L.

    2015-01-01

    Quantifying the magnitude and dynamics of protein oxidation during cell signaling is technically challenging. Computational modeling provides tractable, quantitative methods to test hypotheses of redox mechanisms that may be simultaneously operative during signal transduction. The interleukin-4 (IL-4) pathway, which has previously been reported to induce reactive oxygen species and oxidation of PTP1B, may be controlled by several other putative mechanisms of redox regulation; widespread proteomic thiol oxidation observed via 2D redox differential gel electrophoresis upon IL-4 treatment suggests more than one redox-sensitive protein implicated in this pathway. Through computational modeling and a model selection strategy that relied on characteristic STAT6 phosphorylation dynamics of IL-4 signaling, we identified reversible protein tyrosine phosphatase (PTP) oxidation as the primary redox regulatory mechanism in the pathway. A systems-level model of IL-4 signaling was developed that integrates synchronous pan-PTP oxidation with ROS-independent mechanisms. The model quantitatively predicts the dynamics of IL-4 signaling over a broad range of new redox conditions, offers novel hypotheses about regulation of JAK/STAT signaling, and provides a framework for interrogating putative mechanisms involving receptor-initiated oxidation. PMID:26562652

  20. Dynamic Redox Regulation of IL-4 Signaling.

    PubMed

    Dwivedi, Gaurav; Gran, Margaret A; Bagchi, Pritha; Kemp, Melissa L

    2015-11-01

    Quantifying the magnitude and dynamics of protein oxidation during cell signaling is technically challenging. Computational modeling provides tractable, quantitative methods to test hypotheses of redox mechanisms that may be simultaneously operative during signal transduction. The interleukin-4 (IL-4) pathway, which has previously been reported to induce reactive oxygen species and oxidation of PTP1B, may be controlled by several other putative mechanisms of redox regulation; widespread proteomic thiol oxidation observed via 2D redox differential gel electrophoresis upon IL-4 treatment suggests more than one redox-sensitive protein implicated in this pathway. Through computational modeling and a model selection strategy that relied on characteristic STAT6 phosphorylation dynamics of IL-4 signaling, we identified reversible protein tyrosine phosphatase (PTP) oxidation as the primary redox regulatory mechanism in the pathway. A systems-level model of IL-4 signaling was developed that integrates synchronous pan-PTP oxidation with ROS-independent mechanisms. The model quantitatively predicts the dynamics of IL-4 signaling over a broad range of new redox conditions, offers novel hypotheses about regulation of JAK/STAT signaling, and provides a framework for interrogating putative mechanisms involving receptor-initiated oxidation. PMID:26562652

  1. Comprehensive logic based analyses of Toll-like receptor 4 signal transduction pathway.

    PubMed

    Padwal, Mahesh Kumar; Sarma, Uddipan; Saha, Bhaskar

    2014-01-01

    Among the 13 TLRs in the vertebrate systems, only TLR4 utilizes both Myeloid differentiation factor 88 (MyD88) and Toll/Interleukin-1 receptor (TIR)-domain-containing adapter interferon-β-inducing Factor (TRIF) adaptors to transduce signals triggering host-protective immune responses. Earlier studies on the pathway combined various experimental data in the form of one comprehensive map of TLR signaling. But in the absence of adequate kinetic parameters quantitative mathematical models that reveal emerging systems level properties and dynamic inter-regulation among the kinases/phosphatases of the TLR4 network are not yet available. So, here we used reaction stoichiometry-based and parameter independent logical modeling formalism to build the TLR4 signaling network model that captured the feedback regulations, interdependencies between signaling kinases and phosphatases and the outcome of simulated infections. The analyses of the TLR4 signaling network revealed 360 feedback loops, 157 negative and 203 positive; of which, 334 loops had the phosphatase PP1 as an essential component. The network elements' interdependency (positive or negative dependencies) in perturbation conditions such as the phosphatase knockout conditions revealed interdependencies between the dual-specific phosphatases MKP-1 and MKP-3 and the kinases in MAPK modules and the role of PP2A in the auto-regulation of Calmodulin kinase-II. Our simulations under the specific kinase or phosphatase gene-deficiency or inhibition conditions corroborated with several previously reported experimental data. The simulations to mimic Yersinia pestis and E. coli infections identified the key perturbation in the network and potential drug targets. Thus, our analyses of TLR4 signaling highlights the role of phosphatases as key regulatory factors in determining the global interdependencies among the network elements; uncovers novel signaling connections; identifies potential drug targets for infections. PMID:24699232

  2. Microwave signal processing with photorefractive dynamic holography

    NASA Astrophysics Data System (ADS)

    Fotheringham, Edeline B.

    Have you ever found yourself listening to the music playing from the closest stereo rather than to the bromidic (uninspiring) person speaking to you? Your ears receive information from two sources but your brain listens to only one. What if your cell phone could distinguish among signals sharing the same bandwidth too? There would be no "full" channels to stop you from placing or receiving a call. This thesis presents a nonlinear optical circuit capable of distinguishing uncorrelated signals that have overlapping temporal bandwidths. This so called autotuning filter is the size of a U.S. quarter dollar and requires less than 3 mW of optical power to operate. It is basically an oscillator in which the losses are compensated with dynamic holographic gain. The combination of two photorefractive crystals in the resonator governs the filter's winner-take-all dynamics through signal-competition for gain. This physical circuit extracts what is mathematically referred to as the largest principal component of its spatio-temporal input space. The circuit's practicality is demonstrated by its incorporation in an RF-photonic system. An unknown mixture of unknown microwave signals, received by an antenna array, constitutes the input to the system. The output electronically returns one of the original microwave signals. The front-end of the system down converts the 10 GHz microwave signals and amplifies them before the signals phase modulate optical beams. The optical carrier is suppressed from these beams so that it may not be considered as a signal itself to the autotuning filter. The suppression is achieved with two-beam coupling in a single photorefractive crystal. The filter extracts the more intense of the signals present on the carrier-suppressed input beams. The detection of the extracted signal restores the microwave signal to an electronic form. The system, without the receiving antenna array, is packaged in a 13 x 18 x 6″ briefcase. Its power consumption equals that

  3. Pattern Selection by Dynamical Biochemical Signals

    PubMed Central

    Palau-Ortin, David; Formosa-Jordan, Pau; Sancho, José M.; Ibañes, Marta

    2015-01-01

    The development of multicellular organisms involves cells to decide their fate upon the action of biochemical signals. This decision is often spatiotemporally coordinated such that a spatial pattern arises. The dynamics that drive pattern formation usually involve genetic nonlinear interactions and positive feedback loops. These complex dynamics may enable multiple stable patterns for the same conditions. Under these circumstances, pattern formation in a developing tissue involves a selection process: why is a certain pattern formed and not another stable one? Herein we computationally address this issue in the context of the Notch signaling pathway. We characterize a dynamical mechanism for developmental selection of a specific pattern through spatiotemporal changes of the control parameters of the dynamics, in contrast to commonly studied situations in which initial conditions and noise determine which pattern is selected among multiple stable ones. This mechanism can be understood as a path along the parameter space driven by a sequence of biochemical signals. We characterize the selection process for three different scenarios of this dynamical mechanism that can take place during development: the signal either 1) acts in all the cells at the same time, 2) acts only within a cluster of cells, or 3) propagates along the tissue. We found that key elements for pattern selection are the destabilization of the initial pattern, the subsequent exploration of other patterns determined by the spatiotemporal symmetry of the parameter changes, and the speeds of the path compared to the timescales of the pattern formation process itself. Each scenario enables the selection of different types of patterns and creates these elements in distinct ways, resulting in different features. Our approach extends the concept of selection involved in cellular decision-making, usually applied to cell-autonomous decisions, to systems that collectively make decisions through cell

  4. Decoding dynamic Ca2+ signaling in the vascular endothelium

    PubMed Central

    Taylor, Mark S.; Francis, Michael

    2014-01-01

    Although acute and chronic vasoregulation is inherently driven by endothelial Ca2+, control and targeting of Ca2+-dependent signals are poorly understood. Recent studies have revealed localized and dynamic endothelial Ca2+ events comprising an intricate signaling network along the vascular intima. Discrete Ca2+ transients emerging from both internal stores and plasmalemmal cation channels couple to specific membrane K+ channels, promoting endothelial hyperpolarization and vasodilation. The spatiotemporal tuning of these signals, rather than global Ca2+ elevation, appear to direct endothelial functions under physiologic conditions. In fact, altered patterns of dynamic Ca2+ signaling may underlie essential endothelial dysfunction in a variety of cardiovascular diseases. Advances in imaging approaches and analyses in recent years have allowed for detailed detection, quantification, and evaluation of Ca2+ dynamics in intact endothelium. Here, we discuss recent insights into these signals, including their sources of origination and their functional encoding. We also address key aspects of data acquisition and interpretation, including broad applications of automated high-content analysis. PMID:25452732

  5. Structural and functional protein network analyses predict novel signaling functions for rhodopsin

    PubMed Central

    Kiel, Christina; Vogt, Andreas; Campagna, Anne; Chatr-aryamontri, Andrew; Swiatek-de Lange, Magdalena; Beer, Monika; Bolz, Sylvia; Mack, Andreas F; Kinkl, Norbert; Cesareni, Gianni; Serrano, Luis; Ueffing, Marius

    2011-01-01

    Orchestration of signaling, photoreceptor structural integrity, and maintenance needed for mammalian vision remain enigmatic. By integrating three proteomic data sets, literature mining, computational analyses, and structural information, we have generated a multiscale signal transduction network linked to the visual G protein-coupled receptor (GPCR) rhodopsin, the major protein component of rod outer segments. This network was complemented by domain decomposition of protein–protein interactions and then qualified for mutually exclusive or mutually compatible interactions and ternary complex formation using structural data. The resulting information not only offers a comprehensive view of signal transduction induced by this GPCR but also suggests novel signaling routes to cytoskeleton dynamics and vesicular trafficking, predicting an important level of regulation through small GTPases. Further, it demonstrates a specific disease susceptibility of the core visual pathway due to the uniqueness of its components present mainly in the eye. As a comprehensive multiscale network, it can serve as a basis to elucidate the physiological principles of photoreceptor function, identify potential disease-associated genes and proteins, and guide the development of therapies that target specific branches of the signaling pathway. PMID:22108793

  6. Dynamic behaviour of a rolling tyre: Experimental and numerical analyses

    NASA Astrophysics Data System (ADS)

    Gonzalez Diaz, Cristobal; Kindt, Peter; Middelberg, Jason; Vercammen, Stijn; Thiry, Christophe; Close, Roland; Leyssens, Jan

    2016-03-01

    Based on the results of experimental and numerical analyses, the effect of rotation on the tyre dynamic behaviour is investigated. Better understanding of these effects will further improve the ability to control and optimize the noise and vibrations that result from the interaction between the road surface and the rolling tyre. Therefore, more understanding in the complex tyre dynamic properties will contribute to develop tyre design strategies to lower the tyre/road noise while less affecting other tyre performances. The presented work is performed in the framework of the European industry-academia project TIRE-DYN, with partners Goodyear, Katholieke Universiteit Leuven and LMS International. The effect of rotation on the tyre dynamic behaviour is quantified for different operating conditions of the tyre, such as load, air pressure and rotation speed. By means of experimental and numerical analyses, the effects of rotation on the tyre dynamic behaviour are studied.

  7. STIM proteins: dynamic calcium signal transducers

    PubMed Central

    Soboloff, Jonathan; Rothberg, Brad S.; Madesh, Muniswamy; Gill, Donald L.

    2012-01-01

    Stromal interaction molecule (STIM) proteins function in cells as dynamic coordinators of cellular calcium (Ca2+) signals. Spanning the endoplasmic reticulum (ER) membrane, they sense tiny changes in the levels of Ca2+ stored within the ER lumen. As ER Ca2+ is released to generate primary Ca2+ signals, STIM proteins undergo an intricate activation reaction and rapidly translocate into junctions formed between the ER and the plasma membrane. There, STIM proteins tether and activate the highly Ca2+-selective Orai channels to mediate finely controlled Ca2+ signals and to homeostatically balance cellular Ca2+. Details are emerging on the remarkable organization within these STIM-induced junctional microdomains and the identification of new regulators and alternative target proteins for STIM. PMID:22914293

  8. Dynamic Analysis of Integrated Signaling, Metabolic, and Regulatory Networks

    PubMed Central

    Eddy, James A.; Papin, Jason A.

    2008-01-01

    Extracellular cues affect signaling, metabolic, and regulatory processes to elicit cellular responses. Although intracellular signaling, metabolic, and regulatory networks are highly integrated, previous analyses have largely focused on independent processes (e.g., metabolism) without considering the interplay that exists among them. However, there is evidence that many diseases arise from multifunctional components with roles throughout signaling, metabolic, and regulatory networks. Therefore, in this study, we propose a flux balance analysis (FBA)–based strategy, referred to as integrated dynamic FBA (idFBA), that dynamically simulates cellular phenotypes arising from integrated networks. The idFBA framework requires an integrated stoichiometric reconstruction of signaling, metabolic, and regulatory processes. It assumes quasi-steady-state conditions for “fast” reactions and incorporates “slow” reactions into the stoichiometric formalism in a time-delayed manner. To assess the efficacy of idFBA, we developed a prototypic integrated system comprising signaling, metabolic, and regulatory processes with network features characteristic of actual systems and incorporating kinetic parameters based on typical time scales observed in literature. idFBA was applied to the prototypic system, which was evaluated for different environments and gene regulatory rules. In addition, we applied the idFBA framework in a similar manner to a representative module of the single-cell eukaryotic organism Saccharomyces cerevisiae. Ultimately, idFBA facilitated quantitative, dynamic analysis of systemic effects of extracellular cues on cellular phenotypes and generated comparable time-course predictions when contrasted with an equivalent kinetic model. Since idFBA solves a linear programming problem and does not require an exhaustive list of detailed kinetic parameters, it may be efficiently scaled to integrated intracellular systems that incorporate signaling, metabolic, and

  9. Akt signaling dynamics in individual cells

    PubMed Central

    Gross, Sean M.; Rotwein, Peter

    2015-01-01

    ABSTRACT The protein kinase Akt (for which there are three isoforms) is a key intracellular mediator of many biological processes, yet knowledge of Akt signaling dynamics is limited. Here, we have constructed a fluorescent reporter molecule in a lentiviral delivery system to assess Akt kinase activity at the single cell level. The reporter, a fusion between a modified FoxO1 transcription factor and clover, a green fluorescent protein, rapidly translocates from the nucleus to the cytoplasm in response to Akt stimulation. Because of its long half-life and the intensity of clover fluorescence, the sensor provides a robust readout that can be tracked for days under a range of biological conditions. Using this reporter, we find that stimulation of Akt activity by IGF-I is encoded into stable and reproducible analog responses at the population level, but that single cell signaling outcomes are variable. This reporter, which provides a simple and dynamic measure of Akt activity, should be compatible with many cell types and experimental platforms, and thus opens the door to new insights into how Akt regulates its biological responses. PMID:26040286

  10. Noise reduction by dynamic signal preemphasis

    NASA Astrophysics Data System (ADS)

    Takeda, Kazuyuki; Takegoshi, K.

    2011-02-01

    In this work we propose an approach to reduce the digitization noise for a given dynamic range, i.e., the number of bits, of an analog to digital converter used in an NMR receiver. In this approach, the receiver gain is dynamically increased so that the free induction decay is recorded in such an emphasized way that the decaying signal is digitized using as many number of bits as possible, and at the stage of data processing, the original signal profile is restored by applying the apodization that compensates the effect of the preemphasis. This approach, which we call APodization after Receiver gain InCrement during Ongoing sequence with Time (APRICOT), is performed in a solid-state system containing a pair of 13C spins, one of which is fully isotopically labeled and the other is naturally abundant. It is demonstrated that the exceedingly smaller peak buried in the digitization noise in the conventional approach can be revealed by employing APRICOT.

  11. Preliminary Analyses of Beidou Signal-In Anomaly Since 2013

    NASA Astrophysics Data System (ADS)

    Wu, Y.; Ren, J.; Liu, W.

    2016-06-01

    As BeiDou navigation system has been operational since December 2012. There is an increasing desire to use multiple constellation to improve positioning performance. The signal-in-space (SIS) anomaly caused by the ground control and the space vehicle is one of the major threats to affect the integrity. For a young Global Navigation Satellite System, knowledge about SIS anomalies in history is very important for not only assessing the SIS integrity performance of a constellation but also providing the assumption for ARAIM (Advanced Receiver Autonomous Integrity Monitoring). In this paper, the broadcast ephemerides and the precise ones are pre-processed for avoiding the false anomaly identification. The SIS errors over the period of Mar. 2013-Feb. 2016 are computed by comparing the broadcast ephemerides with the precise ones. The time offsets between GPST (GPS time) and BDT (BeiDou time) are estimated and removed by an improved estimation algorithm. SIS worst-UREs are computed and a RMS criteria are investigated to identify the SIS anomalies. The results show that the probability of BeiDou SIS anomalies is in 10-3 level in last three years. Even though BeiDou SIS integrity performance currently cannot match the GPS integrity performances, the result indicates that BeiDou has a tendency to improve its integrity performance.

  12. Plant phosphoinositide signaling - dynamics on demand.

    PubMed

    Heilmann, Ingo

    2016-09-01

    Eukaryotic membranes contain small amounts of lipids with regulatory roles. An important class of such regulatory lipids are phosphoinositides (PIs). Within membranes, PIs serve as recruitment signals, as regulators of membrane protein function or as precursors for second messenger production, thereby influencing a multitude of cellular processes with key importance for plant function and development. Plant PIs occur locally and transiently within membrane microdomains, and their abundance is strictly controlled. To understand the functions of the plant PI-network it is important to understand not only downstream PI-effects, but also to identify and characterize factors contributing to dynamic PI formation. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. PMID:26924252

  13. Competitive aggregation dynamics using phase wave signals.

    PubMed

    Sakaguchi, Hidetsugu; Maeyama, Satomi

    2014-10-21

    Coupled equations of the phase equation and the equation of cell concentration n are proposed for competitive aggregation dynamics of slime mold in two dimensions. Phase waves are used as tactic signals of aggregation in this model. Several aggregation clusters are formed initially, and target patterns appear around the localized aggregation clusters. Owing to the competition among target patterns, the number of the localized aggregation clusters decreases, and finally one dominant localized pattern survives. If the phase equation is replaced with the complex Ginzburg-Landau equation, several spiral patterns appear, and n is localized near the center of the spiral patterns. After the competition among spiral patterns, one dominant spiral survives. PMID:24956327

  14. Dynamic membrane patterning, signal localization and polarity in living cells.

    PubMed

    Zamparo, M; Chianale, F; Tebaldi, C; Cosentino-Lagomarsino, M; Nicodemi, M; Gamba, A

    2015-02-01

    We review the molecular and physical aspects of the dynamic localization of signaling molecules on the plasma membranes of living cells. At the nanoscale, clusters of receptors and signaling proteins play an essential role in the processing of extracellular signals. At the microscale, "soft" and highly dynamic signaling domains control the interaction of individual cells with their environment. At the multicellular scale, individual polarity patterns control the forces that shape multicellular aggregates and tissues. PMID:25563791

  15. Fluorescence Ratio Imaging Of Dynamic Intracellular Signals

    NASA Astrophysics Data System (ADS)

    Harootunian, Alec T.; Kao, J. P.; Tsien, Roger Y.

    1989-12-01

    Traditional biochemical assays of cellular messengers require grinding up thousands or millions of cells for each data point. Such destructive measurements use up large amounts of tissue, have poor time resolution, and cannot assess heterogeneity between individual cells or dynamic spatial localizations. Recent technical advances now enable important ionic signals to be continuously imaged inside individual living cells with micron spatial resolution and subsecond time resolution. This methodology relies on the molecular engineering of indicator dyes whose fluorescence is strong and highly sensitive to ions such as Ca2+, H+, or Na+. Binding of these ions shifts the fluorescence excitation spectrum of the corresponding indicator. The ratio of excitation amplitudes at two wavelengths measures the free ion concentration while canceling out intensity variations due to nonuniform cell thickness or dye content. By rapidly alternating between the two ion-sensitive excitation wavelengths, a fluorescence microscope equipped with a low-light television camera and digital image processor can produce dynamic images of intracellular messenger levels. In many populations of cells traditionally assumed to be homogeneous, we find that neighboring individual cells can differ enormously in their cytosolic Ca2+ response to agonist stimulation, some ignoring the stimulus, others raising cytosolic Ca2+ transiently, others showing oscillations. Oscillations have been speculated to be important as a basis for frequency-coding of oscillations. Oscillations have been speculated to be important as a basis for frequency-coding of graded inputs; we are investigating the mechanism of their generation using light flashes to generate pulses of intracellular messengers. Spatial gradients of cytosolic Ca t+ within single cells have been observed in embryos during fertilization and development, neurons exposed to electrical or drug stimulation and in cytotoxic T lymphocytes during killing of target

  16. [Dynamic Pulse Signal Processing and Analyzing in Mobile System].

    PubMed

    Chou, Yongxin; Zhang, Aihua; Ou, Jiqing; Qi, Yusheng

    2015-09-01

    In order to derive dynamic pulse rate variability (DPRV) signal from dynamic pulse signal in real time, a method for extracting DPRV signal was proposed and a portable mobile monitoring system was designed. The system consists of a front end for collecting and wireless sending pulse signal and a mobile terminal. The proposed method is employed to extract DPRV from dynamic pulse signal in mobile terminal, and the DPRV signal is analyzed both in the time domain and the frequency domain and also with non-linear method in real time. The results show that the proposed method can accurately derive DPRV signal in real time, the system can be used for processing and analyzing DPRV signal in real time. PMID:26904868

  17. Analysing connectivity with Granger causality and dynamic causal modelling

    PubMed Central

    Friston, Karl; Moran, Rosalyn; Seth, Anil K

    2013-01-01

    This review considers state-of-the-art analyses of functional integration in neuronal macrocircuits. We focus on detecting and estimating directed connectivity in neuronal networks using Granger causality (GC) and dynamic causal modelling (DCM). These approaches are considered in the context of functional segregation and integration and — within functional integration — the distinction between functional and effective connectivity. We review recent developments that have enjoyed a rapid uptake in the discovery and quantification of functional brain architectures. GC and DCM have distinct and complementary ambitions that are usefully considered in relation to the detection of functional connectivity and the identification of models of effective connectivity. We highlight the basic ideas upon which they are grounded, provide a comparative evaluation and point to some outstanding issues. PMID:23265964

  18. Space station static and dynamic analyses using parallel methods

    NASA Technical Reports Server (NTRS)

    Gupta, V.; Newell, J.; Storaasli, O.; Baddourah, M.; Bostic, S.

    1993-01-01

    Algorithms for high-performance parallel computers are applied to perform static analyses of large-scale Space Station finite-element models (FEMs). Several parallel-vector algorithms under development at NASA Langley are assessed. Sparse matrix solvers were found to be more efficient than banded symmetric or iterative solvers for the static analysis of large-scale applications. In addition, new sparse and 'out-of-core' solvers were found superior to substructure (superelement) techniques which require significant additional cost and time to perform static condensation during global FEM matrix generation as well as the subsequent recovery and expansion. A method to extend the fast parallel static solution techniques to reduce the computation time for dynamic analysis is also described. The resulting static and dynamic algorithms offer design economy for preliminary multidisciplinary design optimization and FEM validation against test modes. The algorithms are being optimized for parallel computers to solve one-million degrees-of-freedom (DOF) FEMs. The high-performance computers at NASA afforded effective software development, testing, efficient and accurate solution with timely system response and graphical interpretation of results rarely found in industry. Based on the author's experience, similar cooperation between industry and government should be encouraged for similar large-scale projects in the future.

  19. Strength and dynamic characteristics analyses of wound composite axial impeller

    NASA Astrophysics Data System (ADS)

    Wang, Jifeng; Olortegui-Yume, Jorge; Müller, Norbert

    2012-03-01

    A low cost, light weight, high performance composite material turbomachinery impeller with a uniquely designed blade patterns is analyzed. Such impellers can economically enable refrigeration plants to use water as a refrigerant (R718). A strength and dynamic characteristics analyses procedure is developed to assess the maximum stresses and natural frequencies of these wound composite axial impellers under operating loading conditions. Numerical simulation using FEM for two-dimensional and three-dimensional impellers was investigated. A commercially available software ANSYS is used for the finite element calculations. Analysis is done for different blade geometries and then suggestions are made for optimum design parameters. In order to avoid operating at resonance, which can make impellers suffer a significant reduction in the design life, the designer must calculate the natural frequency and modal shape of the impeller to analyze the dynamic characteristics. The results show that using composite Kevlar fiber/epoxy matrix enables the impeller to run at high tip speed and withstand the stresses, no critical speed will be matched during start-up and shut-down, and that mass imbalances of the impeller shall not pose a critical problem.

  20. Dynamic and static error analyses of neutron radiography testing

    SciTech Connect

    Joo, H.; Glickstein, S.S.

    1999-03-01

    Neutron radiography systems are being used for real-time visualization of the dynamic behavior as well as time-averaged measurements of spatial vapor fraction distributions for two phase fluids. The data in the form of video images are typically recorded on videotape at 30 frames per second. Image analysis of he video pictures is used to extract time-dependent or time-averaged data. The determination of the average vapor fraction requires averaging of the logarithm of time-dependent intensity measurements of the neutron beam (gray scale distribution of the image) that passes through the fluid. This could be significantly different than averaging the intensity of the transmitted beam and then taking the logarithm of that term. This difference is termed the dynamic error (error in the time-averaged vapor fractions due to the inherent time-dependence of the measured data) and is separate from the static error (statistical sampling uncertainty). Detailed analyses of both sources of errors are discussed.

  1. Bias Analyses of Preclinical and Clinical D2 Dopamine Ligands: Studies with Immediate and Complex Signaling Pathways

    PubMed Central

    Brust, Tarsis F.; Hayes, Michael P.; Roman, David L.; Burris, Kevin D.

    2015-01-01

    G protein–coupled receptors (GPCRs) often activate multiple signaling pathways, and ligands may evoke functional responses through individual pathways. These unique responses provide opportunities for biased or functionally selective ligands to preferentially modulate one signaling pathway over another. Studies with several GPCRs have suggested that selective activation of signaling pathways downstream of a GPCR may lead to safer and more effective drug therapies. The dopamine D2 receptor (D2R) is one of the main drug targets in the therapies for Parkinson’s disease and schizophrenia. Recent studies suggest that selective modulation of individual signaling pathways downstream of the D2R may lead to safer antipsychotic drugs. In the present study, immediate effectors of the D2R (i.e., Gαi/o, Gβγ, β-arrestin recruitment) and more complex signaling pathways (i.e., extracellular signal-regulated kinase phosphorylation, heterologous sensitization, and dynamic mass redistribution) were examined in response to a series of D2R ligands. This was accomplished using Chinese hamster ovary cells stably expressing the human D2L dopamine receptor in the PathHunter β-Arrestin GPCR Assay Platform. The use of a uniform cellular background was designed to eliminate potential confounds associated with cell-to-cell variability, including expression levels of receptor as well as other components of signal transduction, including G protein subunits. Several well characterized and clinically relevant D2R ligands were evaluated across each signaling pathway in this cellular model. The most commonly used methods to measure ligand bias were compared. Functional selectivity analyses were also used as tools to explore the relative contribution of immediate D2R effectors for the activation of more complex signaling pathways. PMID:25539635

  2. Spatiotemporal dynamics of phosphorylation in lipid second messenger signaling.

    PubMed

    Antal, Corina E; Newton, Alexandra C

    2013-12-01

    The plasma membrane serves as a dynamic interface that relays information received at the cell surface into the cell. Lipid second messengers coordinate signaling on this platform by recruiting and activating kinases and phosphatases. Specifically, diacylglycerol and phosphatidylinositol 3,4,5-trisphosphate activate protein kinase C and Akt, respectively, which then phosphorylate target proteins to transduce downstream signaling. This review addresses how the spatiotemporal dynamics of protein kinase C and Akt signaling can be monitored using genetically encoded reporters and provides information on how the coordination of signaling at protein scaffolds or membrane microdomains affords fidelity and specificity in phosphorylation events. PMID:23788531

  3. How cells process information: Quantification of spatiotemporal signaling dynamics

    PubMed Central

    Ganesan, Ambhighainath; Zhang, Jin

    2012-01-01

    Arguably, one of the foremost distinctions between life and non-living matter is the ability to sense environmental changes and respond appropriately—an ability that is invested in every living cell. Within a single cell, this function is largely carried out by networks of signaling molecules. However, the details of how signaling networks help cells make complicated decisions are still not clear. For instance, how do cells read graded, analog stress signals but convert them into digital live-or-die responses? The answer to such questions may originate from the fact that signaling molecules are not static but dynamic entities, changing in numbers and activity over time and space. In the past two decades, researchers have been able to experimentally monitor signaling dynamics and use mathematical techniques to quantify and abstract general principles of how cells process information. In this review, the authors first introduce and discuss various experimental and computational methodologies that have been used to study signaling dynamics. The authors then discuss the different types of temporal dynamics such as oscillations and bistability that can be exhibited by signaling systems and highlight studies that have investigated such dynamics in physiological settings. Finally, the authors illustrate the role of spatial compartmentalization in regulating cellular responses with examples of second-messenger signaling in cardiac myocytes. PMID:22573643

  4. Temporal and evolutionary dynamics of two-component signaling pathways.

    PubMed

    Salazar, Michael E; Laub, Michael T

    2015-04-01

    Bacteria sense and respond to numerous environmental signals through two-component signaling pathways. Typically, a given stimulus will activate a sensor histidine kinase to autophosphorylate and then phosphotransfer to a cognate response regulator, which can mount an appropriate response. Although these signaling pathways often appear to be simple switches, they can also orchestrate surprisingly sophisticated and complex responses. These temporal dynamics arise from several key regulatory features, including the bifunctionality of histidine kinases as well as positive and negative feedback loops. Two-component signaling pathways are also dynamic on evolutionary time-scales, expanding dramatically in many species through gene duplication and divergence. Here, we review recent work probing the temporal and evolutionary dynamics of two-component signaling systems. PMID:25589045

  5. Temporal and Evolutionary Dynamics of Two-Component Signaling Pathways

    PubMed Central

    Salazar, Michael E.; Laub, Michael T.

    2015-01-01

    Bacteria sense and respond to numerous environmental signals through two-component signaling pathways. Typically, a given stimulus will activate a sensor histidine kinase to autophosphorylate and then phosphotransfer to a cognate response regulator, which can mount an appropriate response. Although these signaling pathways often appear to be simple switches, they can also orchestrate surprisingly sophisticated and complex responses. These temporal dynamics arise from several key regulatory features, including the bifunctionality of histidine kinases as well as positive and negative feedback loops. Two-component signaling pathways are also dynamic on evolutionary time-scales, expanding dramatically in many species through gene duplication and divergence. Here, we review recent work probing the temporal and evolutionary dynamics of two-component signaling systems. PMID:25589045

  6. Dynamical Analyses for Developmental Science: A Primer for Intrigued Scientists

    ERIC Educational Resources Information Center

    DiDonato, M. D.; England, D.; Martin, C. L.; Amazeen, P. G.

    2013-01-01

    Dynamical systems theory is becoming more popular in social and developmental science. However, unfamiliarity with dynamical analysis techniques remains an obstacle for developmentalists who would like to quantitatively apply dynamics in their own research. The goal of this article is to address this issue by clearly and simply presenting several…

  7. Dynamics of Mechanical Signal Transmission through Prestressed Stress Fibers

    PubMed Central

    Hwang, Yongyun; Barakat, Abdul I.

    2012-01-01

    Transmission of mechanical stimuli through the actin cytoskeleton has been proposed as a mechanism for rapid long-distance mechanotransduction in cells; however, a quantitative understanding of the dynamics of this transmission and the physical factors governing it remains lacking. Two key features of the actin cytoskeleton are its viscoelastic nature and the presence of prestress due to actomyosin motor activity. We develop a model of mechanical signal transmission through prestressed viscoelastic actin stress fibers that directly connect the cell surface to the nucleus. The analysis considers both temporally stationary and oscillatory mechanical signals and accounts for cytosolic drag on the stress fibers. To elucidate the physical parameters that govern mechanical signal transmission, we initially focus on the highly simplified case of a single stress fiber. The results demonstrate that the dynamics of mechanical signal transmission depend on whether the applied force leads to transverse or axial motion of the stress fiber. For transverse motion, mechanical signal transmission is dominated by prestress while fiber elasticity has a negligible effect. Conversely, signal transmission for axial motion is mediated uniquely by elasticity due to the absence of a prestress restoring force. Mechanical signal transmission is significantly delayed by stress fiber material viscosity, while cytosolic damping becomes important only for longer stress fibers. Only transverse motion yields the rapid and long-distance mechanical signal transmission dynamics observed experimentally. For simple networks of stress fibers, mechanical signals are transmitted rapidly to the nucleus when the fibers are oriented largely orthogonal to the applied force, whereas the presence of fibers parallel to the applied force slows down mechanical signal transmission significantly. The present results suggest that cytoskeletal prestress mediates rapid mechanical signal transmission and allows

  8. Dynamic Vibrotactile Signals for Forward Collision Avoidance Warning Systems

    PubMed Central

    Meng, Fanxing; Gray, Rob; Ho, Cristy; Ahtamad, Mujthaba

    2015-01-01

    Objective: Four experiments were conducted in order to assess the effectiveness of dynamic vibrotactile collision-warning signals in potentially enhancing safe driving. Background: Auditory neuroscience research has demonstrated that auditory signals that move toward a person are more salient than those that move away. If this looming effect were found to extend to the tactile modality, then it could be utilized in the context of in-car warning signal design. Method: The effectiveness of various vibrotactile warning signals was assessed using a simulated car-following task. The vibrotactile warning signals consisted of dynamic toward-/away-from-torso cues (Experiment 1), dynamic versus static vibrotactile cues (Experiment 2), looming-intensity- and constant-intensity-toward-torso cues (Experiment 3), and static cues presented on the hands or on the waist, having either a low or high vibration intensity (Experiment 4). Results: Braking reaction times (BRTs) were significantly faster for toward-torso as compared to away-from-torso cues (Experiments 1 and 2) and static cues (Experiment 2). This difference could not have been attributed to differential responses to signals delivered to different body parts (i.e., the waist vs. hands; Experiment 4). Embedding a looming-intensity signal into the toward-torso signal did not result in any additional BRT benefits (Experiment 3). Conclusion: Dynamic vibrotactile cues that feel as though they are approaching the torso can be used to communicate information concerning external events, resulting in a significantly faster reaction time to potential collisions. Application: Dynamic vibrotactile warning signals that move toward the body offer great potential for the design of future in-car collision-warning system. PMID:25850161

  9. Marginal Utility of Conditional Sensitivity Analyses for Dynamic Models

    EPA Science Inventory

    Background/Question/MethodsDynamic ecological processes may be influenced by many factors. Simulation models thatmimic these processes often have complex implementations with many parameters. Sensitivityanalyses are subsequently used to identify critical parameters whose uncertai...

  10. Dynamic loads analyses of flexible airplanes - New and existing techniques

    NASA Technical Reports Server (NTRS)

    Pototzky, A. S.; Perry, B., III

    1985-01-01

    This paper reviews existing techniques for calculating dynamic loads for flexible airplanes and presents a new technique. The new technique involves the summation-of-forces method of writing dynamic loads equations. Until now this form of the dynamic loads equations has been formulated in the frequency domain. The new technique uses s-plane approximation methods (previously applied only to the equations of motion) to transform the dynamic loads equations from a second-order frequency-domain formulation with frequency-dependent coefficients into a linear-time-invariant state-space formulation. Several numerical examples demonstrate the usefulfness of the new technique and the high quality of the results. In addition, a convergence investigation establishes that the summation-of-forces method converges more quickly (that is, with fewer modes) than does the mode displacement method.

  11. Dynamic Signal Tracking in a Simple V1 Spiking Model.

    PubMed

    Lajoie, Guillaume; Young, Lai-Sang

    2016-09-01

    This work is part of an effort to understand the neural basis for our visual system's ability, or failure, to accurately track moving visual signals. We consider here a ring model of spiking neurons, intended as a simplified computational model of a single hypercolumn of the primary visual cortex of primates. Signals that consist of edges with time-varying orientations localized in space are considered. Our model is calibrated to produce spontaneous and driven firing rates roughly consistent with experiments, and our two main findings, for which we offer dynamical explanation on the level of neuronal interactions, are the following. First, we have documented consistent transient overshoots in signal perception following signal switches due to emergent interactions of the E- and I-populations. Second, for continuously moving signals, we have found that accuracy is considerably lower at reversals of orientation than when continuing in the same direction (as when the signal is a rotating bar). To measure performance, we use two metrics, called fidelity and reliability, to compare signals reconstructed by the system to the ones presented and assess trial-to-trial variability. We propose that the same population mechanisms responsible for orientation selectivity also impose constraints on dynamic signal tracking that manifest in perception failures consistent with psychophysical observations. PMID:27391687

  12. All-optical signal processing using dynamic Brillouin gratings

    NASA Astrophysics Data System (ADS)

    Santagiustina, Marco; Chin, Sanghoon; Primerov, Nicolay; Ursini, Leonora; Thévenaz, Luc

    2013-04-01

    The manipulation of dynamic Brillouin gratings in optical fibers is demonstrated to be an extremely flexible technique to achieve, with a single experimental setup, several all-optical signal processing functions. In particular, all-optical time differentiation, time integration and true time reversal are theoretically predicted, and then numerically and experimentally demonstrated. The technique can be exploited to process both photonic and ultra-wide band microwave signals, so enabling many applications in photonics and in radio science.

  13. All-optical signal processing using dynamic Brillouin gratings

    PubMed Central

    Santagiustina, Marco; Chin, Sanghoon; Primerov, Nicolay; Ursini, Leonora; Thévenaz, Luc

    2013-01-01

    The manipulation of dynamic Brillouin gratings in optical fibers is demonstrated to be an extremely flexible technique to achieve, with a single experimental setup, several all-optical signal processing functions. In particular, all-optical time differentiation, time integration and true time reversal are theoretically predicted, and then numerically and experimentally demonstrated. The technique can be exploited to process both photonic and ultra-wide band microwave signals, so enabling many applications in photonics and in radio science. PMID:23549159

  14. Regulation of Mitoflash Biogenesis and Signaling by Mitochondrial Dynamics.

    PubMed

    Li, Wenwen; Sun, Tao; Liu, Beibei; Wu, Di; Qi, Wenfeng; Wang, Xianhua; Ma, Qi; Cheng, Heping

    2016-01-01

    Mitochondria are highly dynamic organelles undergoing constant network reorganization and exhibiting stochastic signaling events in the form of mitochondrial flashes (mitoflashes). Here we investigate whether and how mitochondrial network dynamics regulate mitoflash biogenesis and signaling. We found that mitoflash frequency was largely invariant when network fragmentized or redistributed in the absence of mitofusin (Mfn) 1, Mfn2, or Kif5b. However, Opa1 deficiency decreased spontaneous mitoflash frequency due to superimposing changes in respiratory function, whereas mitoflash response to non-metabolic stimulation was unchanged despite network fragmentation. In Drp1- or Mff-deficient cells whose mitochondria hyperfused into a single whole-cell reticulum, the frequency of mitoflashes of regular amplitude and duration was again unaltered, although brief and low-amplitude "miniflashes" emerged because of improved detection ability. As the network reorganized, however, the signal mass of mitoflash signaling was dynamically regulated in accordance with the degree of network connectivity. These findings demonstrate a novel functional role of mitochondrial network dynamics and uncover a magnitude- rather than frequency-modulatory mechanism in the regulation of mitoflash signaling. In addition, our data support a stochastic trigger model for the ignition of mitoflashes. PMID:27623243

  15. Study of simulating dynamic polarization laser echo signal

    NASA Astrophysics Data System (ADS)

    Yang, Di; Liu, Qing; Zhan, Yong-hong; Zeng, Chang-e.

    2014-12-01

    In the test for the laser seeker in the hardware-in-loop simulation, acquiring the effect of polarization laser echo wave to optical stress polarization of the seeker and to the polarization guidance performance was not considered. A new method to generating the dynamic polarization laser echo signal was provided based on the scene model; furthermore, the method to adding the polarization characters to the energy scene was introduced. At last, the insufficient of the method to generating and simulating the dynamic polarization signal was analyzed.

  16. Analysing Dynamical Behavior of Cellular Networks via Stochastic Bifurcations

    PubMed Central

    Zakharova, Anna; Kurths, Jürgen; Vadivasova, Tatyana; Koseska, Aneta

    2011-01-01

    The dynamical structure of genetic networks determines the occurrence of various biological mechanisms, such as cellular differentiation. However, the question of how cellular diversity evolves in relation to the inherent stochasticity and intercellular communication remains still to be understood. Here, we define a concept of stochastic bifurcations suitable to investigate the dynamical structure of genetic networks, and show that under stochastic influence, the expression of given proteins of interest is defined via the probability distribution of the phase variable, representing one of the genes constituting the system. Moreover, we show that under changing stochastic conditions, the probabilities of expressing certain concentration values are different, leading to different functionality of the cells, and thus to differentiation of the cells in the various types. PMID:21647432

  17. Dynamic Ca(2+) signal modalities in the vascular endothelium.

    PubMed

    Taylor, Mark S; Francis, Michael; Qian, Xun; Solodushko, Viktoriya

    2012-07-01

    The endothelium is vital to normal vasoregulation. Although acute vasodilation associated with broad endothelial Ca(2+) elevation is well known, the control and targeting of Ca(2+) -dependent signals in the endothelium are poorly understood. Recent studies have revealed localized IP(3) -motivated Ca(2+) events occurring basally along the intima that may provide the fundamental basis for various endothelial influences. Here, we provide an overview of dynamic endothelial Ca(2+) signals and discuss the potential role of these signals in constant endothelial control of arterial tone and the titration of functional responses in vivo. In particular, we focus on the functional architecture contributing to the properties and ultimate impact of these signals, and explore new avenues in evaluating their prevalence and specific modalities in intact tissue. Finally, we discuss spatial and temporal effector recruitment through modification of these inherent signals. It is suggested that endothelial Ca(2+) signaling is a continuum in which the specific framework of store-release components and cellular targets along the endothelium allows for differential modes of Ca(2+) signal expansion and distinctive profiles of effector recruitment. The precise composition and distribution of these inherent components may underlie dynamic endothelial control and specialized functions of different vascular beds. PMID:22443172

  18. Dynamic analysis of heartbeat rate signals of epileptics using multidimensional phase space reconstruction approach

    NASA Astrophysics Data System (ADS)

    Su, Zhi-Yuan; Wu, Tzuyin; Yang, Po-Hua; Wang, Yeng-Tseng

    2008-04-01

    The heartbeat rate signal provides an invaluable means of assessing the sympathetic-parasympathetic balance of the human autonomic nervous system and thus represents an ideal diagnostic mechanism for detecting a variety of disorders such as epilepsy, cardiac disease and so forth. The current study analyses the dynamics of the heartbeat rate signal of known epilepsy sufferers in order to obtain a detailed understanding of the heart rate pattern during a seizure event. In the proposed approach, the ECG signals are converted into heartbeat rate signals and the embedology theorem is then used to construct the corresponding multidimensional phase space. The dynamics of the heartbeat rate signal are then analyzed before, during and after an epileptic seizure by examining the maximum Lyapunov exponent and the correlation dimension of the attractors in the reconstructed phase space. In general, the results reveal that the heartbeat rate signal transits from an aperiodic, highly-complex behaviour before an epileptic seizure to a low dimensional chaotic motion during the seizure event. Following the seizure, the signal trajectories return to a highly-complex state, and the complex signal patterns associated with normal physiological conditions reappear.

  19. Signal-detection analyses of conditional discrimination and delayed matching-to-sample performance.

    PubMed Central

    Alsop, Brent

    2004-01-01

    Quantitative analyses of stimulus control and reinforcer control in conditional discriminations and delayed matching-to-sample procedures often encounter a problem; it is not clear how to analyze data when subjects have not made errors. The present article examines two common methods for overcoming this problem. Monte Carlo simulations of performance demonstrated that both methods introduced systematic deviations into the results, and that there were genuine risks of drawing misleading conclusions concerning behavioral models of signal detection and animal short-term memory. PMID:15484871

  20. Phosphoproteomic analyses reveal novel cross-modulation mechanisms between two signaling pathways in yeast.

    PubMed

    Vaga, Stefania; Bernardo-Faura, Marti; Cokelaer, Thomas; Maiolica, Alessio; Barnes, Christopher A; Gillet, Ludovic C; Hegemann, Björn; van Drogen, Frank; Sharifian, Hoda; Klipp, Edda; Peter, Matthias; Saez-Rodriguez, Julio; Aebersold, Ruedi

    2014-01-01

    Cells respond to environmental stimuli via specialized signaling pathways. Concurrent stimuli trigger multiple pathways that integrate information, predominantly via protein phosphorylation. Budding yeast responds to NaCl and pheromone via two mitogen-activated protein kinase cascades, the high osmolarity, and the mating pathways, respectively. To investigate signal integration between these pathways, we quantified the time-resolved phosphorylation site dynamics after pathway co-stimulation. Using shotgun mass spectrometry, we quantified 2,536 phosphopeptides across 36 conditions. Our data indicate that NaCl and pheromone affect phosphorylation events within both pathways, which thus affect each other at more levels than anticipated, allowing for information exchange and signal integration. We observed a pheromone-induced down-regulation of Hog1 phosphorylation due to Gpd1, Ste20, Ptp2, Pbs2, and Ptc1. Distinct Ste20 and Pbs2 phosphosites responded differently to the two stimuli, suggesting these proteins as key mediators of the information exchange. A set of logic models was then used to assess the role of measured phosphopeptides in the crosstalk. Our results show that the integration of the response to different stimuli requires complex interconnections between signaling pathways. PMID:25492886

  1. Phosphoproteomic analyses reveal novel cross-modulation mechanisms between two signaling pathways in yeast

    PubMed Central

    Vaga, Stefania; Bernardo-Faura, Marti; Cokelaer, Thomas; Maiolica, Alessio; Barnes, Christopher A; Gillet, Ludovic C; Hegemann, Björn; van Drogen, Frank; Sharifian, Hoda; Klipp, Edda; Peter, Matthias; Saez-Rodriguez, Julio; Aebersold, Ruedi

    2014-01-01

    Cells respond to environmental stimuli via specialized signaling pathways. Concurrent stimuli trigger multiple pathways that integrate information, predominantly via protein phosphorylation. Budding yeast responds to NaCl and pheromone via two mitogen-activated protein kinase cascades, the high osmolarity, and the mating pathways, respectively. To investigate signal integration between these pathways, we quantified the time-resolved phosphorylation site dynamics after pathway co-stimulation. Using shotgun mass spectrometry, we quantified 2,536 phosphopeptides across 36 conditions. Our data indicate that NaCl and pheromone affect phosphorylation events within both pathways, which thus affect each other at more levels than anticipated, allowing for information exchange and signal integration. We observed a pheromone-induced down-regulation of Hog1 phosphorylation due to Gpd1, Ste20, Ptp2, Pbs2, and Ptc1. Distinct Ste20 and Pbs2 phosphosites responded differently to the two stimuli, suggesting these proteins as key mediators of the information exchange. A set of logic models was then used to assess the role of measured phosphopeptides in the crosstalk. Our results show that the integration of the response to different stimuli requires complex interconnections between signaling pathways. PMID:25492886

  2. Improved Aerodynamic Influence Coefficients for Dynamic Aeroelastic Analyses

    NASA Astrophysics Data System (ADS)

    Gratton, Patrice

    2011-12-01

    Currently at Bombardier Aerospace, aeroelastic analyses are performed using the Doublet Lattice Method (DLM) incorporated in the NASTRAN solver. This method proves to be very reliable and fast in preliminary design stages where wind tunnel experimental results are often not available. Unfortunately, the geometric simplifications and limitations of the DLM, based on the lifting surfaces theory, reduce the ability of this method to give reliable results for all flow conditions, particularly in transonic flow. Therefore, a new method has been developed involving aerodynamic data from high-fidelity CFD codes which solve the Euler or Navier-Stokes equations. These new aerodynamic loads are transmitted to the NASTRAN aeroelastic module through improved aerodynamic influence coefficients (AIC). A cantilevered wing model is created from the Global Express structural model and a set of natural modes is calculated for a baseline configuration of the structure. The baseline mode shapes are then combined with an interpolation scheme to deform the 3-D CFD mesh necessary for Euler and Navier-Stokes analyses. An uncoupled approach is preferred to allow aerodynamic information from different CFD codes. Following the steady state CFD analyses, pressure differences ( DeltaCp), calculated between the deformed models and the original geometry, lead to aerodynamic loads which are transferred to the DLM model. A modal-based AIC method is applied to the aerodynamic matrices of NASTRAN based on a least-square approximation to evaluate aerodynamic loads of a different wing configuration which displays similar types of mode shapes. The methodology developed in this research creates weighting factors based on steady CFD analyses which have an equivalent reduced frequency of zero. These factors are applied to both the real and imaginary part of the aerodynamic matrices as well as all reduced frequencies used in the PK-Method which solves flutter problems. The modal-based AIC method

  3. Coupled Thermo-Mechanical Analyses of Dynamically Loaded Rubber Cylinders

    NASA Technical Reports Server (NTRS)

    Johnson, Arthur R.; Chen, Tzi-Kang

    2000-01-01

    A procedure that models coupled thermo-mechanical deformations of viscoelastic rubber cylinders by employing the ABAQUS finite element code is described. Computational simulations of hysteretic heating are presented for several tall and short rubber cylinders both with and without a steel disk at their centers. The cylinders are compressed axially and are then cyclically loaded about the compressed state. The non-uniform hysteretic heating of the rubber cylinders containing a steel disk is presented. The analyses performed suggest that the coupling procedure should be considered for further development as a design tool for rubber degradation studies.

  4. Aggregation Dynamics Using Phase Wave Signals and Branching Patterns

    NASA Astrophysics Data System (ADS)

    Sakaguchi, Hidetsugu; Kusagaki, Takuma

    2016-09-01

    The aggregation dynamics of slime mold is studied using coupled equations of phase ϕ and cell concentration n. Phase waves work as tactic signals for aggregation. Branching structures appear during the aggregation. A stationary branching pattern appears like a river network, if cells are uniformly supplied into the system.

  5. Dynamic multiprotein assemblies shape the spatial structure of cell signaling.

    PubMed

    Nussinov, Ruth; Jang, Hyunbum

    2014-01-01

    Cell signaling underlies critical cellular decisions. Coordination, efficiency as well as fail-safe mechanisms are key elements. How the cell ensures that these hallmarks are at play are important questions. Cell signaling is often viewed as taking place through discrete and cross-talking pathways; oftentimes these are modularized to emphasize distinct functions. While simple, convenient and clear, such models largely neglect the spatial structure of cell signaling; they also convey inter-modular (or inter-protein) spatial separation that may not exist. Here our thesis is that cell signaling is shaped by a network of multiprotein assemblies. While pre-organized, the assemblies and network are loose and dynamic. They contain transiently-associated multiprotein complexes which are often mediated by scaffolding proteins. They are also typically anchored in the membrane, and their continuum may span the cell. IQGAP1 scaffolding protein which binds proteins including Raf, calmodulin, Mek, Erk, actin, and tens more, with actin shaping B-cell (and likely other) membrane-anchored nanoclusters and allosterically polymerizing in dynamic cytoskeleton formation, and Raf anchoring in the membrane along with Ras, provides a striking example. The multivalent network of dynamic proteins and lipids, with specific interactions forming and breaking, can be viewed as endowing gel-like properties. Collectively, this reasons that efficient, productive and reliable cell signaling takes place primarily through transient, preorganized and cooperative protein-protein interactions spanning the cell rather than stochastic, diffusion-controlled processes. PMID:25046855

  6. Defective insulin signaling and mitochondrial dynamics in diabetic cardiomyopathy

    PubMed Central

    Westermeier, Francisco; Navarro-Marquez, Mario; López-Crisosto, Camila; Bravo-Sagua, Roberto; Quiroga, Clara; Bustamante, Mario; Verdejo, Hugo E.; Zalaquett, Ricardo; Ibacache, Mauricio; Parra, Valentina; Castro, Pablo F.; Rothermel, Beverly A.; Hill, Joseph A.; Lavandero, Sergio

    2015-01-01

    Diabetic cardiomyopathy (DCM) is a common consequence of longstanding type 2 diabetes mellitus (T2DM) and encompasses structural, morphological, functional, and metabolic abnormalities in the heart. Myocardial energy metabolism depends on mitochondria, which must generate sufficient ATP to meet the high energy demands of the myocardium. Dysfunctional mitochondria are involved in the pathophysiology of diabetic heart disease. A large body of evidence implicates myocardial insulin resistance in the pathogenesis of DCM. Recent studies show that insulin signaling influences myocardial energy metabolism by impacting cardiomyocyte mitochondrial dynamics and function under physiological conditions. However, comprehensive understanding of molecular mechanisms linking insulin signaling and changes in the architecture of the mitochondrial network in diabetic cardiomyopathy is lacking. This review summarizes our current understanding of how defective insulin signaling impacts cardiac function in diabetic cardiomyopathy and discusses the potential role of mitochondrial dynamics. PMID:25686534

  7. Probing the dynamic nature of signalling pathways by IMAC and SELDI-tof MS.

    PubMed

    Foucher, Aude L; Späth, Gerald F; Pemberton, Iain K

    2010-01-01

    One major obstacle to the analysis of signalling pathways is the dynamic nature of signalling response to environmental stimuli. To overcome this limitation we applied immobilized metal affinity chromatography (IMAC) in combination with SELDI-tof MS to investigate the temporal variation of protein phosphorylation. We analysed the phospho-proteome variations in our model organism, Leishmania donovani, in response to changes in pH and temperature, which induce differentiation from promastigotes to amastigotes. Investigation of total cell extracts did not allow promastigote and amastigote life cycle stages to be distinguished. However, using IMAC enriched samples, the pattern and intensity of phospho-proteins analysed distinguished both stages reproducibly. Approximately 61% of the phospho-proteins analysed were significantly different in abundance (p<0.02). Of these 61%, 73% showed an increased phosphorylation in promastigotes while 27% showed an increase phosphorylation in amastigotes. The workflow developed is currently being applied to the temporal analysis of environmental stimuli. PMID:20590411

  8. Three-dimensional nonlinear transient dynamic accident analyses of waste packages

    SciTech Connect

    Bennett, S.M.; Ceylan, Z.; Doering, T.W.

    1996-02-01

    The analyses presented in this paper describe advanced methods of performing accident analyses by using finite element analysis. The models created to obtain solutions for these accident conditions are three-dimensional solid models which are solved in transient dynamic analyses. Previous solutions to similar problems were found by applying dynamic load factors to static solutions. By solving the analyses using the transient dynamic approach, the use of dynamic load factors is eliminated, leading to more accurate solutions and better control of the amount of conservatism included in the design. These analyses are also performed using nonlinear material properties to represent the elastic and plastic regions of stress and strain. The use of elastic-plastic material properties is necessary to accurately determine if breach of waste package containment occurs.

  9. Unsteady flow and dynamic response analyses for helicopter rotor blades

    NASA Technical Reports Server (NTRS)

    Bratanow, T.

    1979-01-01

    Research is presented on helicopter rotor blade vibration and on two and three dimensional analyses of unsteady incompressible viscous flow past oscillating helicopter rotor blades. A summary is presented of the two international research collaborations which resulted from the NASA project: the collaboration under the auspices of NATO between the University of Wisconsin-Milwaukee, University of Brussels, Belgium and the Aerodynamics Research Establishment in Goettingen, West Germany, and the collaboration under the auspices of the National Science Foundation between UWM and the University of Hamburg and the Ship Research Establishment in Hamburg, West Germany. A summary is given of the benefits from the NASA project to UWM, the College of Engineering and Applied Science, and the participants on the project.

  10. Thermo-Mechanical Analyses of Dynamically Loaded Rubber Cylinders

    NASA Technical Reports Server (NTRS)

    Johnson, Arthur R.; Chen, Tzi-Kang

    2002-01-01

    Thick rubber components are employed by the Army to carry large loads. In tanks, rubber covers road wheels and track systems to protect roadways. It is difficult for design engineers to simulate the details of the hysteretic heating for large strain viscoelastic deformations. In this study, an approximation to the viscoelastic energy dissipated per unit time is investigated for use in estimating mechanically induced viscoelastic heating. Coupled thermo-mechanical simulations of large cyclic deformations of rubber cylinders are presented. The cylinders are first compressed axially and then cyclically loaded about the compressed state. Details of the algorithm and some computational issues are discussed. The coupled analyses are conducted for tall and short rubber cylinders both with and without imbedded metal disks.

  11. Dynamic and thermal analyses of flexible structures in orbit

    NASA Astrophysics Data System (ADS)

    Lin, Chijie

    Due to the launch cost and functional requirements, space structures, such as satellite antenna, deployable structures, solar sails, the space station, and solar panels, are necessarily built lightweight, large, and very flexible. These space structures undergo large orbital rigid body motions as well as large structural deformations caused by gravitational force and other disturbances, such as shuttle jet impingement loading, deployment factor, thermal effects, and debris impact. It is of utmost importance to study thoroughly the dynamic behavior of flexible structures in orbit under various external forces. In this study, first a finite element methodology program based on the absolute nodal coordinate formulation is developed to determine the coupled structural and orbital response of the flexible structure under gravitational and external loading, i.e., gravitational force, impact force, and jet impingement, and thermal loading. It is found from the simulation results that pitch and structural response of the flexible structures are greatly impacted by the initial and loading conditions, such as orbit eccentricity, initial misalignment, etc. The absolute nodal coordinate formulation may lead to inaccurate results due to the fact that the orbit radius is used for element coordinate, which is much greater than the amplitude of the pitch (attitude) motion and deformations of the orbiting structures. Therefore, to improve the accuracy of structural response in the simulation, a floating (moving) frame that is attached with the orbiting structure's center of mass and that moves parallel to the inertia frame fixed at the Earth's center is introduced to separate the attitude motion and structural deformation from the orbit radius. The finite element formulation is developed in this parallel reference frame system for two and three dimensional beam structures. It is then used to study dynamic response of flexible structures in two and three dimensional orbits. In some

  12. MRI dynamic range and its compatibility with signal transmission media

    NASA Astrophysics Data System (ADS)

    Gabr, Refaat E.; Schär, Michael; Edelstein, Arthur D.; Kraitchman, Dara L.; Bottomley, Paul A.; Edelstein, William A.

    2009-06-01

    As the number of MRI phased array coil elements grows, interactions among cables connecting them to the system receiver become increasingly problematic. Fiber optic or wireless links would reduce electromagnetic interference, but their dynamic range (DR) is generally less than that of coaxial cables. Raw MRI signals, however, have a large DR because of the high signal amplitude near the center of k-space. Here, we study DR in MRI in order to determine the compatibility of MRI multicoil imaging with non-coaxial cable signal transmission. Since raw signal data are routinely discarded, we have developed an improved method for estimating the DR of MRI signals from conventional magnitude images. Our results indicate that the DR of typical surface coil signals at 3 T for human subjects is less than 88 dB, even for three-dimensional acquisition protocols. Cardiac and spine coil arrays had a maximum DR of less than 75 dB and head coil arrays less than 88 dB. The DR derived from magnitude images is in good agreement with that measured from raw data. The results suggest that current analog fiber optic links, with a spurious-free DR of 60-70 dB at 500 kHz bandwidth, are not by themselves adequate for transmitting MRI data from volume or array coils with DR ˜90 dB. However, combining analog links with signal compression might make non-coaxial cable signal transmission viable.

  13. Classifying transient signals with nonlinear dynamic filter banks

    SciTech Connect

    Brush, J.S.

    1996-06-01

    In recent years, several specific advances in the study of chaotic processes have been made which appear to have immediate applicability to signal processing. This paper describes two applications of one of these advances, nonlinear modeling, to signal detection & classification, in particular for short-lived or transient or signals. The first method uses the coefficients from an adaptively fit model as a set of features for signal detection and classification. In the second method, a library of predictive nonlinear dynamic equations is used as a filter bank, and statistics on the prediction residuals are used to form feature vectors for input data segments. These feature vectors provide a mechanism for detecting and classifying model transients at signal-to-noise ratios as low as {minus}10 dB, even when the generating dynamics of the transient signals are not present in the filter bank. The second method and some validating experiments are described in detail. {copyright} {ital 1996 American Institute of Physics.}

  14. Mapping growth-factor-modulated Akt signaling dynamics.

    PubMed

    Gross, Sean M; Rotwein, Peter

    2016-05-15

    Growth factors alter cellular behavior through shared signaling cascades, raising the question of how specificity is achieved. Here, we have determined how growth factor actions are encoded into Akt signaling dynamics by real-time tracking of a fluorescent sensor. In individual cells, Akt activity was encoded in an analog pattern, with similar latencies (∼2 min) and half-maximal peak response times (range of 5-8 min). Yet, different growth factors promoted dose-dependent and heterogeneous changes in signaling dynamics. Insulin treatment caused sustained Akt activity, whereas EGF or PDGF-AA promoted transient signaling; PDGF-BB produced sustained responses at higher concentrations, but short-term effects at low doses, actions that were independent of the PDGF-α receptor. Transient responses to EGF were caused by negative feedback at the receptor level, as a second treatment yielded minimal responses, whereas parallel exposure to IGF-I caused full Akt activation. Small-molecule inhibitors reduced PDGF-BB signaling to transient responses, but only decreased the magnitude of IGF-I actions. Our observations reveal distinctions among growth factors that use shared components, and allow us to capture the consequences of receptor-specific regulatory mechanisms on Akt signaling. PMID:27044757

  15. Fractal and complex network analyses of protein molecular dynamics

    NASA Astrophysics Data System (ADS)

    Zhou, Yuan-Wu; Liu, Jin-Long; Yu, Zu-Guo; Zhao, Zhi-Qin; Anh, Vo

    2014-12-01

    Based on protein molecular dynamics, we investigate the fractal properties of energy, pressure and volume time series using the multifractal detrended fluctuation analysis (MF-DFA) and the topological and fractal properties of their converted horizontal visibility graphs (HVGs). The energy parameters of protein dynamics we considered are bonded potential, angle potential, dihedral potential, improper potential, kinetic energy, Van der Waals potential, electrostatic potential, total energy and potential energy. The shape of the h(q) curves from MF-DFA indicates that these time series are multifractal. The numerical values of the exponent h(2) of MF-DFA show that the series of total energy and potential energy are non-stationary and anti-persistent; the other time series are stationary and persistent apart from series of pressure (with H≈0.5 indicating the absence of long-range correlation). The degree distributions of their converted HVGs show that these networks are exponential. The results of fractal analysis show that fractality exists in these converted HVGs. For each energy, pressure or volume parameter, it is found that the values of h(2) of MF-DFA on the time series, exponent λ of the exponential degree distribution and fractal dimension dB of their converted HVGs do not change much for different proteins (indicating some universality). We also found that after taking average over all proteins, there is a linear relationship between (from MF-DFA on time series) and of the converted HVGs for different energy, pressure and volume.

  16. Discrete dynamic modeling of T cell survival signaling networks

    NASA Astrophysics Data System (ADS)

    Zhang, Ranran

    2009-03-01

    Biochemistry-based frameworks are often not applicable for the modeling of heterogeneous regulatory systems that are sparsely documented in terms of quantitative information. As an alternative, qualitative models assuming a small set of discrete states are gaining acceptance. This talk will present a discrete dynamic model of the signaling network responsible for the survival and long-term competence of cytotoxic T cells in the blood cancer T-LGL leukemia. We integrated the signaling pathways involved in normal T cell activation and the known deregulations of survival signaling in leukemic T-LGL, and formulated the regulation of each network element as a Boolean (logic) rule. Our model suggests that the persistence of two signals is sufficient to reproduce all known deregulations in leukemic T-LGL. It also indicates the nodes whose inactivity is necessary and sufficient for the reversal of the T-LGL state. We have experimentally validated several model predictions, including: (i) Inhibiting PDGF signaling induces apoptosis in leukemic T-LGL. (ii) Sphingosine kinase 1 and NFκB are essential for the long-term survival of T cells in T-LGL leukemia. (iii) T box expressed in T cells (T-bet) is constitutively activated in the T-LGL state. The model has identified potential therapeutic targets for T-LGL leukemia and can be used for generating long-term competent CTL necessary for tumor and cancer vaccine development. The success of this model, and of other discrete dynamic models, suggests that the organization of signaling networks has an determining role in their dynamics. Reference: R. Zhang, M. V. Shah, J. Yang, S. B. Nyland, X. Liu, J. K. Yun, R. Albert, T. P. Loughran, Jr., Network Model of Survival Signaling in LGL Leukemia, PNAS 105, 16308-16313 (2008).

  17. Translatome analyses capture of opposing tissue-specific brassinosteroid signals orchestrating root meristem differentiation.

    PubMed

    Vragović, Kristina; Sela, Ayala; Friedlander-Shani, Lilach; Fridman, Yulia; Hacham, Yael; Holland, Neta; Bartom, Elizabeth; Mockler, Todd C; Savaldi-Goldstein, Sigal

    2015-01-20

    The mechanisms ensuring balanced growth remain a critical question in developmental biology. In plants, this balance relies on spatiotemporal integration of hormonal signaling pathways, but the understanding of the precise contribution of each hormone is just beginning to take form. Brassinosteroid (BR) hormone is shown here to have opposing effects on root meristem size, depending on its site of action. BR is demonstrated to both delay and promote onset of stem cell daughter differentiation, when acting in the outer tissue of the root meristem, the epidermis, and the innermost tissue, the stele, respectively. To understand the molecular basis of this phenomenon, a comprehensive spatiotemporal translatome mapping of Arabidopsis roots was performed. Analyses of wild type and mutants featuring different distributions of BR revealed autonomous, tissue-specific gene responses to BR, implying its contrasting tissue-dependent impact on growth. BR-induced genes were primarily detected in epidermal cells of the basal meristem zone and were enriched by auxin-related genes. In contrast, repressed BR genes prevailed in the stele of the apical meristem zone. Furthermore, auxin was found to mediate the growth-promoting impact of BR signaling originating in the epidermis, whereas BR signaling in the stele buffered this effect. We propose that context-specific BR activity and responses are oppositely interpreted at the organ level, ensuring coherent growth. PMID:25561530

  18. An Integrated Signaling-Encryption Mechanism to Reduce Error Propagation in Wireless Communications: Performance Analyses

    SciTech Connect

    Olama, Mohammed M; Matalgah, Mustafa M; Bobrek, Miljko

    2015-01-01

    Traditional encryption techniques require packet overhead, produce processing time delay, and suffer from severe quality of service deterioration due to fades and interference in wireless channels. These issues reduce the effective transmission data rate (throughput) considerably in wireless communications, where data rate with limited bandwidth is the main constraint. In this paper, performance evaluation analyses are conducted for an integrated signaling-encryption mechanism that is secure and enables improved throughput and probability of bit-error in wireless channels. This mechanism eliminates the drawbacks stated herein by encrypting only a small portion of an entire transmitted frame, while the rest is not subject to traditional encryption but goes through a signaling process (designed transformation) with the plaintext of the portion selected for encryption. We also propose to incorporate error correction coding solely on the small encrypted portion of the data to drastically improve the overall bit-error rate performance while not noticeably increasing the required bit-rate. We focus on validating the signaling-encryption mechanism utilizing Hamming and convolutional error correction coding by conducting an end-to-end system-level simulation-based study. The average probability of bit-error and throughput of the encryption mechanism are evaluated over standard Gaussian and Rayleigh fading-type channels and compared to the ones of the conventional advanced encryption standard (AES).

  19. Observational analyses and idealized numerical simulations of African wave dynamics

    NASA Astrophysics Data System (ADS)

    Smith, Travis Allen

    The role of the Tropical Easterly Jet (TEJ) in West African rainfall climatology has received little attention in the research community to date. Therefore, this dissertation will examine the instabilities and wave activity associated with the TEJ and their implications regarding interannual rainfall variability over western Africa. First, the instability of the TEJ is examined using potential vorticity (PV) concepts to contrast wet and dry years in West Africa. Analyses of the meridional PV gradient indicate an abrupt shift in both location and magnitude of the instability associated with the TEJ during the transition from wet to dry years in the Sahel. Additionally, the signs of the climatological anomalies of PV at the TEJ level strongly reflect the four primary modes (wet, dry, wet dipole, and dry dipole) of interannual rainfall variability in West Africa. Several examples of PV perturbation analyses at the TEJ level confirm that the upper-level development of African Easterly Waves (AEWs) differs considerably between the two periods. These results support recent observations and modeling studies that suggest that the interaction between the TEJ and the African Easterly Jet (AEJ) plays an important role in the development and structure of AEWs. In addition to the observational study, a multi-layer primitive equation model is utilized to examine easterly wave activity and vertical motion patterns based on the juxtaposition of the three primary jets located over western Africa. Idealized simulations based on the basic states of the low-level westerly jet (LLWJ), African Easterly Jet (AEJ), and the Tropical Easterly Jet (TEJ) for several anomalously wet and dry years in the Sahel are studied. Results are compared to several linearized GCM simulations that are initialized with NCEP observational data. Results show that the location, intensity, and scale of wave perturbations are sensitive to the position and intensity of the jets. Vertical motion patterns also

  20. Signal classification using global dynamical models, Part I: Theory

    SciTech Connect

    Kadtke, J.; Kremliovsky, M.

    1996-06-01

    Detection and classification of signals is one of the principal areas of signal processing, and the utilization of nonlinear information has long been considered as a way of improving performance beyond standard linear (e.g. spectral) techniques. Here, we develop a method for using global models of chaotic dynamical systems theory to define a signal classification processing chain, which is sensitive to nonlinear correlations in the data. We use it to demonstrate classification in high noise regimes (negative SNR), and argue that classification probabilities can be directly computed from ensemble statistics in the model coefficient space. We also develop a modification for non-stationary signals (i.e. transients) using non-autonomous ODEs. In Part II of this paper, we demonstrate the analysis on actual open ocean acoustic data from marine biologics. {copyright} {ital 1996 American Institute of Physics.}

  1. Dynamic Analyses of Polymer Surface using Dielectric Relaxation

    NASA Astrophysics Data System (ADS)

    Ishii, Masashi

    A new dielectric relaxation measurement technique for analyses of polymer surface was developed. In this technique, in order to maintain the original surface, probing electrodes were placed away from the sample, and a liquid to stabilize the surface was filled in the space between the sample and the electrodes. From difference of dielectric relaxation between a bare polyimide and gold-coated polyimide, the surface of polyimide was characterized. The surface dielectric relaxation spectrum at room temperature depended on the liquid species: The Debye relaxation was obtained for ethanol, while multiple-relaxation was observed for ultrapure water. A thermal activation process of the polyimide surface was investigated using temperature-controlled ultrapure water, and it was found that the surface transited from the multiple-relaxation to the Debye relaxation at ∼95°C. In the Debye relaxation condition, the surface can be characterized with a capacitance independent of the liquid species. The capacitance estimated at 110 pF provided a characteristic curve of the polyimide surface. A surface model was proposed to explain the thermal activation process.

  2. Dynamic Bayesian filtering for real-time seismic analyses

    SciTech Connect

    Blough, D.K.; Rohay, A.C.; Anderson, K.K.; Nicholson, W.L.

    1994-04-01

    State space modeling, which includes techniques such as the Kalman filter, has been used to analyze many non-stationary time series. The ability of these dynamic models to adapt and track changes in the underlying process makes them attractive for application to the real-time analysis of three-component seismic waveforms. The authors are investigating the application of state space models formulated as Bayesian time series models to phase detection, polarization, and spectrogram estimation of seismograms. This approach removes the need to specify data windows in the time series for time averaging estimation (e.g., spectrum estimation). They are using this model to isolate particular seismic phases based on polarization parameters that are determined at a spectrum of frequencies. They plan to use polarization parameters, frequency spectra, and magnitudes to discriminate between different types of seismic sources. They present the application of this technique to artificial time series and to several real seismic events including the Non-Proliferation Experiment (NPE) two nuclear tests and three earthquakes from the Nevada Test site, as recorded on several regional broadband seismic stations. A preliminary result of this analysis indicates that earthquakes and explosions can potentially be discriminated on the bass of the polarization characteristics of scattered seismic phases. However, the chemical (NPE) and nuclear explosions appear to have very similar polarization characteristics.

  3. Signal integration enhances the dynamic range in neuronal systems

    NASA Astrophysics Data System (ADS)

    Gollo, Leonardo L.; Mirasso, Claudio; Eguíluz, Víctor M.

    2012-04-01

    The dynamic range measures the capacity of a system to discriminate the intensity of an external stimulus. Such an ability is fundamental for living beings to survive: to leverage resources and to avoid danger. Consequently, the larger is the dynamic range, the greater is the probability of survival. We investigate how the integration of different input signals affects the dynamic range, and in general the collective behavior of a network of excitable units. By means of numerical simulations and a mean-field approach, we explore the nonequilibrium phase transition in the presence of integration. We show that the firing rate in random and scale-free networks undergoes a discontinuous phase transition depending on both the integration time and the density of integrator units. Moreover, in the presence of external stimuli, we find that a system of excitable integrator units operating in a bistable regime largely enhances its dynamic range.

  4. GNSS Signal Tracking Performance Improvement for Highly Dynamic Receivers by Gyroscopic Mounting Crystal Oscillator.

    PubMed

    Abedi, Maryam; Jin, Tian; Sun, Kewen

    2015-01-01

    In this paper, the efficiency of the gyroscopic mounting method is studied for a highly dynamic GNSS receiver's reference oscillator for reducing signal loss. Analyses are performed separately in two phases, atmospheric and upper atmospheric flights. Results show that the proposed mounting reduces signal loss, especially in parts of the trajectory where its probability is the highest. This reduction effect appears especially for crystal oscillators with a low elevation angle g-sensitivity vector. The gyroscopic mounting influences frequency deviation or jitter caused by dynamic loads on replica carrier and affects the frequency locked loop (FLL) as the dominant tracking loop in highly dynamic GNSS receivers. In terms of steady-state load, the proposed mounting mostly reduces the frequency deviation below the one-sigma threshold of FLL (1σ(FLL)). The mounting method can also reduce the frequency jitter caused by sinusoidal vibrations and reduces the probability of signal loss in parts of the trajectory where the other error sources accompany this vibration load. In the case of random vibration, which is the main disturbance source of FLL, gyroscopic mounting is even able to suppress the disturbances greater than the three-sigma threshold of FLL (3σ(FLL)). In this way, signal tracking performance can be improved by the gyroscopic mounting method for highly dynamic GNSS receivers. PMID:26404286

  5. GNSS Signal Tracking Performance Improvement for Highly Dynamic Receivers by Gyroscopic Mounting Crystal Oscillator

    PubMed Central

    Abedi, Maryam; Jin, Tian; Sun, Kewen

    2015-01-01

    In this paper, the efficiency of the gyroscopic mounting method is studied for a highly dynamic GNSS receiver’s reference oscillator for reducing signal loss. Analyses are performed separately in two phases, atmospheric and upper atmospheric flights. Results show that the proposed mounting reduces signal loss, especially in parts of the trajectory where its probability is the highest. This reduction effect appears especially for crystal oscillators with a low elevation angle g-sensitivity vector. The gyroscopic mounting influences frequency deviation or jitter caused by dynamic loads on replica carrier and affects the frequency locked loop (FLL) as the dominant tracking loop in highly dynamic GNSS receivers. In terms of steady-state load, the proposed mounting mostly reduces the frequency deviation below the one-sigma threshold of FLL (1σFLL). The mounting method can also reduce the frequency jitter caused by sinusoidal vibrations and reduces the probability of signal loss in parts of the trajectory where the other error sources accompany this vibration load. In the case of random vibration, which is the main disturbance source of FLL, gyroscopic mounting is even able to suppress the disturbances greater than the three-sigma threshold of FLL (3σFLL). In this way, signal tracking performance can be improved by the gyroscopic mounting method for highly dynamic GNSS receivers. PMID:26404286

  6. Distinct Signaling Roles of Ceramide Species in Yeast Revealed Through Systematic Perturbation and Systems Biology Analyses

    PubMed Central

    Montefusco, David J.; Chen, Lujia; Matmati, Nabil; Lu, Songjian; Newcomb, Benjamin; Cooper, Gregory F.; Hannun, Yusuf A.; Lu, Xinghua

    2014-01-01

    Ceramide, the central molecule of sphingolipid metabolism, is an important bioactive molecule participating in cellular regulatory events and having implications for disease. A challenge in deciphering ceramide signaling emanates from the myriad of ceramide species that exist and the possibility that many of them may have distinct functions. Here, we applied systems biology and molecular approaches to perturb ceramide metabolism in the yeast (Saccharomyces cerevisiae) and inferred causal relationships between ceramide species and their potential targets by combining lipidomic, genomic, and transcriptomic analyses. We find that during heat stress distinct metabolic mechanisms control the abundance of different groups of ceramide species. Additionally, distinct groups of ceramide species regulated different sets of functionally related genes, indicating that specific sub-groups of lipids participated in different regulatory pathways. These results indicate a previously unrecognized complexity and versatility of lipid-mediated cell regulation. PMID:24170935

  7. Unveiling Hidden Dynamics of Hippo Signalling: A Systems Analysis

    PubMed Central

    Shin, Sung-Young; Nguyen, Lan K.

    2016-01-01

    The Hippo signalling pathway has recently emerged as an important regulator of cell apoptosis and proliferation with significant implications in human diseases. In mammals, the pathway contains the core kinases MST1/2, which phosphorylate and activate LATS1/2 kinases. The pro-apoptotic function of the MST/LATS signalling axis was previously linked to the Akt and ERK MAPK pathways, demonstrating that the Hippo pathway does not act alone but crosstalks with other signalling pathways to coordinate network dynamics and cellular outcomes. These crosstalks were characterised by a multitude of complex regulatory mechanisms involving competitive protein-protein interactions and phosphorylation mediated feedback loops. However, how these different mechanisms interplay in different cellular contexts to drive the context-specific network dynamics of Hippo-ERK signalling remains elusive. Using mathematical modelling and computational analysis, we uncovered that the Hippo-ERK network can generate highly diverse dynamical profiles that can be clustered into distinct dose-response patterns. For each pattern, we offered mechanistic explanation that defines when and how the observed phenomenon can arise. We demonstrated that Akt displays opposing, dose-dependent functions towards ERK, which are mediated by the balance between the Raf-1/MST2 protein interaction module and the LATS1 mediated feedback regulation. Moreover, Ras displays a multi-functional role and drives biphasic responses of both MST2 and ERK activities; which are critically governed by the competitive protein interaction between MST2 and Raf-1. Our study represents the first in-depth and systematic analysis of the Hippo-ERK network dynamics and provides a concrete foundation for future studies. PMID:27527217

  8. Unveiling Hidden Dynamics of Hippo Signalling: A Systems Analysis.

    PubMed

    Shin, Sung-Young; Nguyen, Lan K

    2016-01-01

    The Hippo signalling pathway has recently emerged as an important regulator of cell apoptosis and proliferation with significant implications in human diseases. In mammals, the pathway contains the core kinases MST1/2, which phosphorylate and activate LATS1/2 kinases. The pro-apoptotic function of the MST/LATS signalling axis was previously linked to the Akt and ERK MAPK pathways, demonstrating that the Hippo pathway does not act alone but crosstalks with other signalling pathways to coordinate network dynamics and cellular outcomes. These crosstalks were characterised by a multitude of complex regulatory mechanisms involving competitive protein-protein interactions and phosphorylation mediated feedback loops. However, how these different mechanisms interplay in different cellular contexts to drive the context-specific network dynamics of Hippo-ERK signalling remains elusive. Using mathematical modelling and computational analysis, we uncovered that the Hippo-ERK network can generate highly diverse dynamical profiles that can be clustered into distinct dose-response patterns. For each pattern, we offered mechanistic explanation that defines when and how the observed phenomenon can arise. We demonstrated that Akt displays opposing, dose-dependent functions towards ERK, which are mediated by the balance between the Raf-1/MST2 protein interaction module and the LATS1 mediated feedback regulation. Moreover, Ras displays a multi-functional role and drives biphasic responses of both MST2 and ERK activities; which are critically governed by the competitive protein interaction between MST2 and Raf-1. Our study represents the first in-depth and systematic analysis of the Hippo-ERK network dynamics and provides a concrete foundation for future studies. PMID:27527217

  9. Signaling networks regulating leukocyte podosome dynamics and function

    PubMed Central

    Dovas, Athanassios; Cox, Dianne

    2011-01-01

    Podosomes are ventral adhesion structures prominent in cells of the myeloid lineage. A common aspect of these cells is that they are highly motile and are required to traverse multiple tissue barriers in order to perform their functions. Recently podosomes have gathered attention from researchers as important cellular structures that can influence cell adhesion, motility and matrix remodeling. Adhesive and soluble ligands act via transmembrane receptors and propagate signals to the leukocyte cytoskeleton via small G proteins of the Rho family, tyrosine kinases and scaffold proteins and are able to induce podosome formation and rearrangements. Manipulation of the signals that regulate podosome formation and dynamics can therefore be a strategy to interfere with leukocyte functions in a multitude of pathological settings, such as infections, atherosclerosis and arthritis. Here, we review the major signaling molecules that act in the formation and regulation of podosomes. PMID:21342664

  10. Fault diagnosis of motor drives using stator current signal analysis based on dynamic time warping

    NASA Astrophysics Data System (ADS)

    Zhen, D.; Wang, T.; Gu, F.; Ball, A. D.

    2013-01-01

    Electrical motor stator current signals have been widely used to monitor the condition of induction machines and their downstream mechanical equipment. The key technique used for current signal analysis is based on Fourier transform (FT) to extract weak fault sideband components from signals predominated with supply frequency component and its higher order harmonics. However, the FT based method has limitations such as spectral leakage and aliasing, leading to significant errors in estimating the sideband components. Therefore, this paper presents the use of dynamic time warping (DTW) to process the motor current signals for detecting and quantifying common faults in a downstream two-stage reciprocating compressor. DTW is a time domain based method and its algorithm is simple and easy to be embedded into real-time devices. In this study DTW is used to suppress the supply frequency component and highlight the sideband components based on the introduction of a reference signal which has the same frequency component as that of the supply power. Moreover, a sliding window is designed to process the raw signal using DTW frame by frame for effective calculation. Based on the proposed method, the stator current signals measured from the compressor induced with different common faults and under different loads are analysed for fault diagnosis. Results show that DTW based on residual signal analysis through the introduction of a reference signal allows the supply components to be suppressed well so that the fault related sideband components are highlighted for obtaining accurate fault detection and diagnosis results. In particular, the root mean square (RMS) values of the residual signal can indicate the differences between the healthy case and different faults under varying discharge pressures. It provides an effective and easy approach to the analysis of motor current signals for better fault diagnosis of the downstream mechanical equipment of motor drives in the time

  11. Motion adaptive signal integration-high dynamic range (MASI-HDR) video processing for dynamic platforms

    NASA Astrophysics Data System (ADS)

    Piacentino, Michael R.; Berends, David C.; Zhang, David C.; Gudis, Eduardo

    2013-05-01

    Two of the biggest challenges in designing U×V vision systems are properly representing high dynamic range scene content using low dynamic range components and reducing camera motion blur. SRI's MASI-HDR (Motion Adaptive Signal Integration-High Dynamic Range) is a novel technique for generating blur-reduced video using multiple captures for each displayed frame while increasing the effective camera dynamic range by four bits or more. MASI-HDR processing thus provides high performance video from rapidly moving platforms in real-world conditions in low latency real time, enabling even the most demanding applications on air, ground and water.

  12. Dynamic tracking down-conversion signal processing method based on reference signal for grating heterodyne interferometer

    NASA Astrophysics Data System (ADS)

    Wang, Guochao; Yan, Shuhua; Zhou, Weihong; Gu, Chenhui

    2012-08-01

    Traditional displacement measurement systems by grating, which purely make use of fringe intensity to implement fringe count and subdivision, have rigid demands for signal quality and measurement condition, so they are not easy to realize measurement with nanometer precision. Displacement measurement with the dual-wavelength and single-grating design takes advantage of the single grating diffraction theory and the heterodyne interference theory, solving quite well the contradiction between large range and high precision in grating displacement measurement. To obtain nanometer resolution and nanometer precision, high-power subdivision of interference fringes must be realized accurately. A dynamic tracking down-conversion signal processing method based on the reference signal is proposed. Accordingly, a digital phase measurement module to realize high-power subdivision on field programmable gate array (FPGA) was designed, as well as a dynamic tracking down-conversion module using phase-locked loop (PLL). Experiments validated that a carrier signal after down-conversion can constantly maintain close to 100 kHz, and the phase-measurement resolution and phase precision are more than 0.05 and 0.2 deg, respectively. The displacement resolution and the displacement precision, corresponding to the phase results, are 0.139 and 0.556 nm, respectively.

  13. Sequence and structural analyses of nuclear export signals in the NESdb database

    PubMed Central

    Xu, Darui; Farmer, Alicia; Collett, Garen; Grishin, Nick V.; Chook, Yuh Min

    2012-01-01

    We compiled >200 nuclear export signal (NES)–containing CRM1 cargoes in a database named NESdb. We analyzed the sequences and three-dimensional structures of natural, experimentally identified NESs and of false-positive NESs that were generated from the database in order to identify properties that might distinguish the two groups of sequences. Analyses of amino acid frequencies, sequence logos, and agreement with existing NES consensus sequences revealed strong preferences for the Φ1-X3-Φ2-X2-Φ3-X-Φ4 pattern and for negatively charged amino acids in the nonhydrophobic positions of experimentally identified NESs but not of false positives. Strong preferences against certain hydrophobic amino acids in the hydrophobic positions were also revealed. These findings led to a new and more precise NES consensus. More important, three-dimensional structures are now available for 68 NESs within 56 different cargo proteins. Analyses of these structures showed that experimentally identified NESs are more likely than the false positives to adopt α-helical conformations that transition to loops at their C-termini and more likely to be surface accessible within their protein domains or be present in disordered or unobserved parts of the structures. Such distinguishing features for real NESs might be useful in future NES prediction efforts. Finally, we also tested CRM1-binding of 40 NESs that were found in the 56 structures. We found that 16 of the NES peptides did not bind CRM1, hence illustrating how NESs are easily misidentified. PMID:22833565

  14. Luminal Ca(2+) dynamics during IP3R mediated signals.

    PubMed

    Lopez, Lucia F; Dawson, Silvina Ponce

    2016-01-01

    The role of cytosolic Ca(2+) on the kinetics of Inositol 1,4,5-triphosphate receptors (IP3Rs) and on the dynamics of IP3R-mediated Ca(2+) signals has been studied at large both experimentally and by modeling. The role of luminal Ca(2+) has not been investigated with that much detail although it has been found that it is relevant for signal termination in the case of Ca(2+) release through ryanodine receptors. In this work we present the results of observing the dynamics of luminal and cytosolic Ca(2+) simultaneously in Xenopus laevis oocytes. Combining observations and modeling we conclude that there is a rapid mechanism that guarantees the availability of free Ca(2+) in the lumen even when a relatively large Ca(2+) release is evoked. Comparing the dynamics of cytosolic and luminal Ca(2+) during a release, we estimate that they are consistent with a 80% of luminal Ca(2+) being buffered. The rapid availability of free luminal Ca(2+) correlates with the observation that the lumen occupies a considerable volume in several regions across the images. PMID:27232767

  15. Luminal Ca2+ dynamics during IP3R mediated signals

    NASA Astrophysics Data System (ADS)

    Lopez, Lucia F.; Ponce Dawson, Silvina

    2016-06-01

    The role of cytosolic Ca2+ on the kinetics of Inositol 1,4,5-triphosphate receptors (IP3Rs) and on the dynamics of IP3R-mediated Ca2+ signals has been studied at large both experimentally and by modeling. The role of luminal Ca2+ has not been investigated with that much detail although it has been found that it is relevant for signal termination in the case of Ca2+ release through ryanodine receptors. In this work we present the results of observing the dynamics of luminal and cytosolic Ca2+ simultaneously in Xenopus laevis oocytes. Combining observations and modeling we conclude that there is a rapid mechanism that guarantees the availability of free Ca2+ in the lumen even when a relatively large Ca2+ release is evoked. Comparing the dynamics of cytosolic and luminal Ca2+ during a release, we estimate that they are consistent with a 80% of luminal Ca2+ being buffered. The rapid availability of free luminal Ca2+ correlates with the observation that the lumen occupies a considerable volume in several regions across the images.

  16. Evolving from static to dynamic signals: evolutionary compensation between two communicative signals

    PubMed Central

    Martins, Emília P.; Ossip-Klein, Alison G.; Zúñiga-Vega, J. Jaime; García, Cuauhcihuatl Vital; Campos, Stephanie M.; Hews, Diana K.

    2015-01-01

    Signals that convey related information may impose selection on each other, creating evolutionary links between different components of the communicative repertoire. Here, we ask about the consequences of the evolutionary loss of one signal (a colour patch) on another (a motion display) in Sceloporus lizards. We present data on male lizards of four species: two pairs of sister taxa representing two independent evolutionary losses of the static colour patch (Sceloporus cozumelae and Sceloporus parvus; Sceloporus siniferus and Sceloporus merriami). Males of the two species that have undergone an evolutionary loss of blue-belly patches (S. cozumelae, S. siniferus) were less active than their blue-bellied sister taxa (S. parvus, S. merriami), consistent with the suggestion that the belly patches were lost to reduce conspicuousness of species with high predation pressure. In contrast, the headbob display appears to have become more, rather than less, conspicuous over evolutionary time. The colour patch is exhibited primarily during aggressive encounters, whereas headbob displays are multifunction signals used in several different contexts, including aggressive encounters. Males of species that have lost the colour patch produced more motion displays, and the structure of those motion displays were more similar to those produced during combat. In both evolutionary episodes, a static colour signal appears to have been replaced by dynamic motion displays that can be turned off in the presence of predators and other unwanted receivers. The predominant pattern is one of evolutionary compensation and interactions between multiple signals that convey related information. PMID:25892737

  17. Platelet receptors and signaling in the dynamics of thrombus formation

    PubMed Central

    Rivera, José; Lozano, María Luisa; Navarro-Núñez, Leyre; Vicente, Vicente

    2009-01-01

    Hemostasis and pathological thrombus formation are dynamic processes that require a co-ordinated series of events involving platelet membrane receptors, bidirectional intracellular signals, and release of platelet proteins and inflammatory substances. This review aims to summarize current knowledge in the key steps in the dynamics of thrombus formation, with special emphasis on the crucial participation of platelet receptors and signaling in this process. Initial tethering and firm adhesion of platelets to the exposed subendothelium is mediated by glycoprotein (GP) Ib/IX/V complex and collagen receptors, GP VI and α2β1 integrin, in the platelet surface, and by VWF and fibrillar collagen in the vascular site. Interactions between these elements are largely influenced by flow and trigger signaling events that reinforce adhesion and promote platelet activation. Thereafter, soluble agonists, ADP, thrombin, TxA2, produced/released at the site of vascular injury act in autocrine and paracrine mode to amplify platelet activation and to recruit circulating platelets to the developing thrombus. Specific interactions of these agonists with their G-protein coupled receptors generate inside-out signaling leading to conformational activation of integrins, in particular αIIbβ3, increasing their ligand affinity. Binding of αIIbβ3 to its ligands, mainly fibrinogen, supports processes such as clot retraction and platelet aggregation. Stabilization of thrombi is supported by the late wave of signaling events promoted by close contact between aggregated platelets. The best known contact-dependent signaling is outside-in signaling through αIb β3, but new ones are being clarified such as those mediated by interaction of Eph receptors with ephrins, or by Sema 4D and Gas-6 binding to their receptors. Finally, newly identified mechanisms appear to control thrombus growth, including back-shifting of activated integrins and actuation of compensatory molecules such as ESAM or PECAM-1

  18. A real-time and fine resolution analyser used to estimate the instantaneous energy distribution of Doppler signals.

    PubMed

    Fan, L; Evans, D H

    1994-01-01

    Doppler ultrasound signal analysers in current use require that the signal be stationary within the time interval of processing, and yield average results for that interval. A real-time instantaneous frequency analyser based on the Wigner distribution function (WDF) has been developed, which provides a means of analysing time-varying signals or signals with short stationary time periods, and also produces results with very high instantaneous temporal resolution without causing significant deterioration of frequency resolution. In addition to the real-time processing, the most recent 2.4 s of Doppler signal is stored in the analyser so that the operator can perform further fine analysis and obtain results with very high resolutions in both the time and frequency domains. The pseudo-instantaneous mean frequency (PIMF) and the Pseudo-Instantaneous Power Distribution (PIPD) are calculated and displayed every 4.0 ms in the real-time processing mode, and with a resolution of between 80 microseconds and 2 ms in the fine resolution analysis mode. The analyser utilises an algorithm developed so that the WDF can be calculated efficiently using the conventional Fast Fourier Transform (FFT) method, and the PIPDs are calculated from data that contribute equally. PMID:7941102

  19. Fluorescent protein-based biosensors: resolving spatiotemporal dynamics of signaling

    PubMed Central

    DiPilato, Lisa M.; Zhang, Jin

    2009-01-01

    Summary Cellular processes are orchestrated by the precise coordination and regulation of molecular events in the cell. Fluorescent protein-based biosensors coupled with live-cell imaging have enabled the visualization of these events in real time and helped shape some of the current concepts of signal transduction, such as spatial compartmentation. The quantitative information produced by these tools has been incorporated into mathematical models that are capable of predicting highly complex and dynamic behaviors of cellular signaling networks, thus providing a systems level understanding of how pathways interact to produce a functional response. Finally, with technological advances in high throughput and in vivo imaging, these molecular tools promise to continually engender significant contributions to our understanding of cellular processes under normal and diseased conditions. PMID:19910237

  20. Application of commercial star couplers to increase signal dynamic range

    SciTech Connect

    Whitcomb, B.M.; Smiley, V.N.; Flurer, R.L.; Nelson, L.K.

    1984-01-01

    Fused biconical tapered (FBT) fiber optic star couplers have been used in a variety of applications at the Nevada Test Site (NTS) in several diagnostic experiments to provide increased dynamic range for the recording devices or to divide the available signal between different recording devices. A number of installation problems have been manifested in this application of FBT couplers. The most severe problem results from the modal selection mechanism inherent in the design of FBT couplers. Substantial work has been done to characterize a variety of commercial couplers for this application.

  1. Multiparticle collision dynamics for diffusion-influenced signaling pathways

    NASA Astrophysics Data System (ADS)

    Strehl, R.; Rohlf, K.

    2016-08-01

    An efficient yet accurate simulation method for modeling diffusion-influenced reaction networks is presented. The method extends existing reactive multiparticle collision dynamics by incorporating species-dependent diffusion coefficients, and developing theoretical expressions for the reactant-dependent diffusion control. This off-lattice particle-based mesoscopic simulation tool is particularly suited for problems in which detailed descriptions of particle trajectories and local reactions are required. Numerical simulations of an intracellular signaling pathway for bacterial chemotaxis are carried out to validate our approach, and to demonstrate its efficiency.

  2. Information for Coarticulation: Static Signal Properties or Formant Dynamics?

    PubMed Central

    Viswanathan, Navin; Magnuson, James S.; Fowler, Carol A.

    2014-01-01

    Perception of a speech segment changes depending on properties of surrounding segments in a phenomenon called compensation for coarticulation (Mann, 1980). The nature of information that drives these perceptual changes is a matter of debate. One account attributes perceptual shifts to low-level auditory system contrast effects based on static portions of the signal (e.g., third formant [F3] center or average frequency; Lotto & Kluender, 1998). An alternative account is that listeners' perceptual shifts result from listeners attuning to the acoustic effects of gestural overlap and that this information for coarticulation is necessarily dynamic (Fowler, 2006). In a pair of experiments, we used sinewave speech precursors to investigate the nature of information for compensation for coarticulation. In Experiment 1, as expected by both accounts, we found that sinewave speech precursors produce shifts in following segments. In Experiment 2, we investigated whether effects in Experiment 1 were driven by static F3 offsets of sinewave speech precursors, or by dynamic relationships among their formants. We temporally reversed F1 and F2 in sinewave precursors, preserving static F3 offset and average F1, F2, and F3 frequencies, but disrupting dynamic formant relationships. Despite having identical F3s, selectively-reversed precursors produced effects that were significantly smaller and restricted to only a small portion of the continuum. We conclude that dynamic formant relations rather than static properties of the precursor provide information for compensation for coarticulation. PMID:24730744

  3. Information for coarticulation: Static signal properties or formant dynamics?

    PubMed

    Viswanathan, Navin; Magnuson, James S; Fowler, Carol A

    2014-06-01

    Perception of a speech segment changes depending on properties of surrounding segments in a phenomenon called compensation for coarticulation (Mann, 1980). The nature of information that drives these perceptual changes is a matter of debate. One account attributes perceptual shifts to low-level auditory system contrast effects based on static portions of the signal (e.g., third formant [F3] center or average frequency; Lotto & Kluender, 1998). An alternative account is that listeners' perceptual shifts result from listeners attuning to the acoustic effects of gestural overlap and that this information for coarticulation is necessarily dynamic (Fowler, 2006). In a pair of experiments, we used sinewave speech precursors to investigate the nature of information for compensation for coarticulation. In Experiment 1, as expected by both accounts, we found that sinewave speech precursors produce shifts in following segments. In Experiment 2, we investigated whether effects in Experiment 1 were driven by static F3 offsets of sinewave speech precursors, or by dynamic relationships among their formants. We temporally reversed F1 and F2 in sinewave precursors, preserving static F3 offset and average F1, F2 and F3 frequencies, but disrupting dynamic formant relationships. Despite having identical F3s, selectively reversed precursors produced effects that were significantly smaller and restricted to only a small portion of the continuum. We conclude that dynamic formant relations rather than static properties of the precursor provide information for compensation for coarticulation. PMID:24730744

  4. Phase-compensation-based dynamic time warping for fault diagnosis using the motor current signal

    NASA Astrophysics Data System (ADS)

    Zhen, D.; Zhao, H. L.; Gu, F.; Ball, A. D.

    2012-05-01

    Dynamic time warping (DTW) is a time-domain-based method and widely used in various similar recognition and data mining applications. This paper presents a phase-compensation-based DTW to process the motor current signals for detecting and quantifying various faults in a two-stage reciprocating compressor under different operating conditions. DTW is an effective method to align two signals for dissimilarity analysis. However, it has drawbacks such as singularities and high computational demands that limit its application in processing motor current signals for obtaining modulation characteristics accurately in diagnosing compressor faults. Therefore, a phase compensation approach is developed to reduce the singularity effect and a sliding window is designed to improve computing efficiency. Based on the proposed method, the motor current signals measured from the compressor induced with different common faults are analysed for fault diagnosis. Results show that residual signal analysis using the phase-compensation-based DTW allows the fault-related sideband features to be resolved more accurately for obtaining reliable fault detection and diagnosis. It provides an effective and easy approach to the analysis of motor current signals for better diagnosis in the time domain in comparison with conventional Fourier-transform-based methods.

  5. Summary of dynamic analyses of the advanced neutron source reactor inner control rods

    SciTech Connect

    Hendrich, W.R.

    1995-08-01

    A summary of the structural dynamic analyses that were instrumental in providing design guidance to the Advanced Neutron source (ANS) inner control element system is presented in this report. The structural analyses and the functional constraints that required certain performance parameters were combined to shape and guide the design effort toward a prediction of successful and reliable control and scram operation to be provided by these inner control rods.

  6. Promoter nucleosome dynamics regulated by signalling through the CTD code.

    PubMed

    Materne, Philippe; Anandhakumar, Jayamani; Migeot, Valerie; Soriano, Ignacio; Yague-Sanz, Carlo; Hidalgo, Elena; Mignion, Carole; Quintales, Luis; Antequera, Francisco; Hermand, Damien

    2015-01-01

    The phosphorylation of the RNA polymerase II C-terminal domain (CTD) plays a key role in delineating transcribed regions within chromatin by recruiting histone methylases and deacetylases. Using genome-wide nucleosome mapping, we show that CTD S2 phosphorylation controls nucleosome dynamics in the promoter of a subset of 324 genes, including the regulators of cell differentiation ste11 and metabolic adaptation inv1. Mechanistic studies on these genes indicate that during gene activation a local increase of phospho-S2 CTD nearby the promoter impairs the phospho-S5 CTD-dependent recruitment of Set1 and the subsequent recruitment of specific HDACs, which leads to nucleosome depletion and efficient transcription. The early increase of phospho-S2 results from the phosphorylation of the CTD S2 kinase Lsk1 by MAP kinase in response to cellular signalling. The artificial tethering of the Lsk1 kinase at the ste11 promoter is sufficient to activate transcription. Therefore, signalling through the CTD code regulates promoter nucleosomes dynamics. PMID:26098123

  7. Promoter nucleosome dynamics regulated by signalling through the CTD code

    PubMed Central

    Materne, Philippe; Anandhakumar, Jayamani; Migeot, Valerie; Soriano, Ignacio; Yague-Sanz, Carlo; Hidalgo, Elena; Mignion, Carole; Quintales, Luis; Antequera, Francisco; Hermand, Damien

    2015-01-01

    The phosphorylation of the RNA polymerase II C-terminal domain (CTD) plays a key role in delineating transcribed regions within chromatin by recruiting histone methylases and deacetylases. Using genome-wide nucleosome mapping, we show that CTD S2 phosphorylation controls nucleosome dynamics in the promoter of a subset of 324 genes, including the regulators of cell differentiation ste11 and metabolic adaptation inv1. Mechanistic studies on these genes indicate that during gene activation a local increase of phospho-S2 CTD nearby the promoter impairs the phospho-S5 CTD-dependent recruitment of Set1 and the subsequent recruitment of specific HDACs, which leads to nucleosome depletion and efficient transcription. The early increase of phospho-S2 results from the phosphorylation of the CTD S2 kinase Lsk1 by MAP kinase in response to cellular signalling. The artificial tethering of the Lsk1 kinase at the ste11 promoter is sufficient to activate transcription. Therefore, signalling through the CTD code regulates promoter nucleosomes dynamics. DOI: http://dx.doi.org/10.7554/eLife.09008.001 PMID:26098123

  8. Pinning down response inhibition in the brain – conjunction analyses of the Stop-signal task

    PubMed Central

    Boehler, CN; Appelbaum, LG; Krebs, RM; Hopf, JM; Woldorff, MG

    2010-01-01

    Successful behavior requires a finely-tuned interplay of initiating and inhibiting motor programs to react effectively to constantly changing environmental demands. One particularly useful paradigm for investigating inhibitory motor control is the Stop-signal task, where already-initiated responses to Go-stimuli are to be inhibited upon the rapid subsequent presentation of a Stop-stimulus (yielding successful and unsuccessful Stop-trials). Despite the extensive use of this paradigm in functional neuroimaging, there is no consensus on which functional comparison to use to characterize response-inhibition-related brain activity. Here, we utilize conjunction analyses of successful and unsuccessful Stop-trials that are each contrasted against a reference condition. This conjunction approach identifies processes common to both Stop-trial types while excluding processes specific to either, thereby capitalizing on the presence of some response-inhibition-related activity in both conditions. Using this approach on fMRI data from human subjects, we identify a network of brain structures that was linked to both types of Stop-trials, including lateral-inferior-frontal and medial-frontal cortical areas and the caudate nucleus. In addition, comparisons with a reference condition matched for visual stimulation identified additional activity in the right inferior parietal cortex that may play a role in enhancing the processing of the Stop-stimuli. Finally, differences in stopping efficacy across subjects were associated with variations in activity in the left anterior insula. However, this region was also associated with general task accuracy (which furthermore correlated directly with stopping efficacy), suggesting that it might actually reflect a more general mechanism of performance control that supports response inhibition in a relatively nonspecific way. PMID:20452445

  9. Dynamic shaping of dopamine signals during probabilistic Pavlovian conditioning

    PubMed Central

    Phillips, Paul E. M.

    2014-01-01

    Cue- and reward-evoked phasic dopamine activity during Pavlovian and operant conditioning paradigms is well correlated with reward-prediction errors from formal reinforcement learning models, which feature teaching signals in the form of discrepancies between actual and expected reward outcomes. Additionally, in learning tasks where conditioned cues probabilistically predict rewards, dopamine neurons show sustained cue-evoked responses that are correlated with the variance of reward and are maximal to cues predicting rewards with a probability of 0.5. Therefore, it has been suggested that sustained dopamine activity after cue presentation encodes the uncertainty of impending reward delivery. In the current study we examined the acquisition and maintenance of these neural correlates using fast-scan cyclic voltammetry in rats implanted with carbon fiber electrodes in the nucleus accumbens core during probabilistic Pavlovian conditioning. The advantage of this technique is that we can sample from the same animal and recording location throughout learning with single trial resolution. We report that dopamine release in the nucleus accumbens core contains correlates of both expected value and variance. A quantitative analysis of these signals throughout learning, and during the ongoing updating process after learning in probabilistic conditions, demonstrates that these correlates are dynamically encoded during these phases. Peak CS-evoked responses are correlated with expected value and predominate during early learning while a variance-correlated sustained CS signal develops during the post-asymptotic updating phase. PMID:25172480

  10. Smad Signaling Dynamics: Insights from a Parsimonious Model

    SciTech Connect

    Wiley, H. S.; Shankaran, Harish

    2008-09-09

    The molecular mechanisms that transmit information from cell surface receptors to the nucleus are exceedingly complex; thus, much effort has been expended in developing computational models to understand these processes. A recent study on modeling the nuclear-cytoplasmic shuttling of Smad2-Smad4 complexes in response to transforming growth factor β (TGF-β) receptor activation has provided substantial insight into how this signaling network translates the degree of TGF-β receptor activation (input) into the amount of nuclear Smad2-Smad4 complexes (output). The study addressed this question by combining a simple, mechanistic model with targeted experiments, an approach that proved particularly powerful for exploring the fundamental properties of a complex signaling network. The mathematical model revealed that Smad nuclear-cytoplasmic dynamics enables a proportional, but time-delayed coupling between the input and the output. As a result, the output can faithfully track gradual changes in the input, while the rapid input fluctuations that constitute signaling noise are dampened out.

  11. Apperceptive signals demonstrating the dynamic disturbance of myocardial ischemia.

    PubMed

    Moulder, P V; Flauto, B; Gallet, B; Galansky, S; Alexander, J A

    1979-01-01

    Analog pressure signals (catheter-tip manometers) from the left atrium, left ventricle, and aorta and a flow signal from the arota were obtained in 25, open-chest, anesthetized dogs in which 115 episodes of ischemia were produced in an area of the left ventricle subtended by the distal left anterior descending coronary artery and its last major diagonal branch. The left ventricular pressure and its first derivative (dP/dt) were displayed as an X-Y loop. The character of this loop went through a unique series of dynamic changes in 110 of the 115 ischemic episodes, indicating that this is a useful tool for monitoring myocardial ischemia. Spectrum pairs of the above signals were analyzed with digital computational transfer functions in 14 ischemic episodes of three experiments and preliminary assessment reveals unique pole and zero changes in many pairs during each episode which also may prove to be a useful indicator of the hemodynamic disturbance incurred during myocardial ischemia. PMID:758716

  12. Response dynamics of phosphorelays suggest their potential utility in cell signalling

    PubMed Central

    Csikász-Nagy, Attila; Cardelli, Luca; Soyer, Orkun S.

    2011-01-01

    Phosphorelays are extended two-component signalling systems found in diverse bacteria, lower eukaryotes and plants. Only few of these systems are characterized, and we still lack a full understanding of their signalling abilities. Here, we aim to achieve a global understanding of phosphorelay signalling and its dynamical properties. We develop a generic model, allowing us to systematically analyse response dynamics under different assumptions. Using this model, we find that the steady-state concentration of phosphorylated protein at the final layer of a phosphorelay is a linearly increasing, but eventually saturating function of the input. In contrast, the intermediate layers can display ultrasensitivity. We find that such ultrasensitivity is a direct result of the phosphorelay biochemistry; shuttling of a single phosphate group from the first to the last layer. The response dynamics of the phosphorelay results in tolerance of cross-talk, especially when it occurs as cross-deactivation. Further, it leads to a high signal-to-noise ratio for the final layer. We find that a relay length of four, which is most commonly observed, acts as a saturating point for these dynamic properties. These findings suggest that phosphorelays could act as a mechanism to reduce noise and effects of cross-talk on the final layer of the relay and enforce its input–response relation to be linear. In addition, our analysis suggests that middle layers of phosphorelays could embed thresholds. We discuss the consequence of these findings in relation to why cells might use phosphorelays along with enzymatic kinase cascades. PMID:20702449

  13. Optimal BLS: Optimizing transit-signal detection for Keplerian dynamics

    NASA Astrophysics Data System (ADS)

    Ofir, Aviv

    2015-08-01

    Transit surveys, both ground- and space-based, have already accumulated a large number of light curves that span several years. We optimize the search for transit signals for both detection and computational efficiencies by assuming that the searched systems can be described by Keplerian, and propagating the effects of different system parameters to the detection parameters. Importnantly, we mainly consider the information content of the transit signal and not any specific algorithm - and use BLS (Kovács, Zucker, & Mazeh 2002) just as a specific example.We show that the frequency information content of the light curve is primarily determined by the duty cycle of the transit signal, and thus the optimal frequency sampling is found to be cubic and not linear. Further optimization is achieved by considering duty-cycle dependent binning of the phased light curve. By using the (standard) BLS, one is either fairly insensitive to long-period planets or less sensitive to short-period planets and computationally slower by a significant factor of ~330 (for a 3 yr long dataset). We also show how the physical system parameters, such as the host star's size and mass, directly affect transit detection. This understanding can then be used to optimize the search for every star individually.By considering Keplerian dynamics explicitly rather than implicitly one can optimally search the transit signal parameter space. The presented Optimal BLS enhances the detectability of both very short and very long period planets, while allowing such searches to be done with much reduced resources and time. The Matlab/Octave source code for Optimal BLS is made available.

  14. Analysis of Signaling Endosome Composition and Dynamics Using SILAC in Embryonic Stem Cell-Derived Neurons*

    PubMed Central

    Debaisieux, Solène; Encheva, Vesela; Chakravarty, Probir; Snijders, Ambrosius P.; Schiavo, Giampietro

    2016-01-01

    Neurons require efficient transport mechanisms such as fast axonal transport to ensure neuronal homeostasis and survival. Neurotrophins and their receptors are conveyed via fast axonal retrograde transport of signaling endosomes to the soma, where they elicit transcriptional responses. Despite the essential roles of signaling endosomes in neuronal differentiation and survival, little is known about their molecular identity, dynamics, and regulation. Gaining a better mechanistic understanding of these organelles and their kinetics is crucial, given the growing evidence linking vesicular trafficking deficits to neurodegeneration. Here, we exploited an affinity purification strategy using the binding fragment of tetanus neurotoxin (HCT) conjugated to monocrystalline iron oxide nanoparticles (MIONs), which in motor neurons, is transported in the same carriers as neurotrophins and their receptors. To quantitatively assess the molecular composition of HCT-containing signaling endosomes, we have developed a protocol for triple Stable Isotope Labeling with Amino acids in Cell culture (SILAC) in embryonic stem cell-derived motor neurons. After HCT internalization, retrograde carriers were magnetically isolated at different time points and subjected to mass-spectrometry and Gene Ontology analyses. This purification strategy is highly specific, as confirmed by the presence of essential regulators of fast axonal transport in the make-up of these organelles. Our results indicate that signaling endosomes undergo a rapid maturation with the acquisition of late endosome markers following a specific time-dependent kinetics. Strikingly, signaling endosomes are specifically enriched in proteins known to be involved in neurodegenerative diseases and neuroinfection. Moreover, we highlighted the presence of novel components, whose precise temporal recruitment on signaling endosomes might be essential for proper sorting and/or transport of these organelles. This study provides the first

  15. Comparisons of several aerodynamic methods for application to dynamic loads analyses

    NASA Technical Reports Server (NTRS)

    Kroll, R. I.; Miller, R. D.

    1976-01-01

    The results of a study are presented in which the applicability at subsonic speeds of several aerodynamic methods for predicting dynamic gust loads on aircraft, including active control systems, was examined and compared. These aerodynamic methods varied from steady state to an advanced unsteady aerodynamic formulation. Brief descriptions of the structural and aerodynamic representations and of the motion and load equations are presented. Comparisons of numerical results achieved using the various aerodynamic methods are shown in detail. From these results, aerodynamic representations for dynamic gust analyses are identified. It was concluded that several aerodynamic methods are satisfactory for dynamic gust analyses of configurations having either controls fixed or active control systems that primarily affect the low frequency rigid body aircraft response.

  16. Detecting early-warning signals for sudden deterioration of complex diseases by dynamical network biomarkers

    PubMed Central

    Chen, Luonan; Liu, Rui; Liu, Zhi-Ping; Li, Meiyi; Aihara, Kazuyuki

    2012-01-01

    Considerable evidence suggests that during the progression of complex diseases, the deteriorations are not necessarily smooth but are abrupt, and may cause a critical transition from one state to another at a tipping point. Here, we develop a model-free method to detect early-warning signals of such critical transitions, even with only a small number of samples. Specifically, we theoretically derive an index based on a dynamical network biomarker (DNB) that serves as a general early-warning signal indicating an imminent bifurcation or sudden deterioration before the critical transition occurs. Based on theoretical analyses, we show that predicting a sudden transition from small samples is achievable provided that there are a large number of measurements for each sample, e.g., high-throughput data. We employ microarray data of three diseases to demonstrate the effectiveness of our method. The relevance of DNBs with the diseases was also validated by related experimental data and functional analysis. PMID:22461973

  17. Dynamic neural activity during stress signals resilient coping.

    PubMed

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

    2016-08-01

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

  18. Are Patient-Specific Joint and Inertial Parameters Necessary for Accurate Inverse Dynamics Analyses of Gait?

    PubMed Central

    Reinbolt, Jeffrey A.; Haftka, Raphael T.; Chmielewski, Terese L.; Fregly, Benjamin J.

    2013-01-01

    Variations in joint parameter values (axis positions and orientations in body segments) and inertial parameter values (segment masses, mass centers, and moments of inertia) as well as kinematic noise alter the results of inverse dynamics analyses of gait. Three-dimensional linkage models with joint constraints have been proposed as one way to minimize the effects of noisy kinematic data. Such models can also be used to perform gait optimizations to predict post-treatment function given pre-treatment gait data. This study evaluates whether accurate patient-specific joint and inertial parameter values are needed in three-dimensional linkage models to produce accurate inverse dynamics results for gait. The study was performed in two stages. First, we used optimization analyses to evaluate whether patient-specific joint and inertial parameter values can be calibrated accurately from noisy kinematic data, and second, we used Monte Carlo analyses to evaluate how errors in joint and inertial parameter values affect inverse dynamics calculations. Both stages were performed using a dynamic, 27 degree-of-freedom, full-body linkage model and synthetic (i.e., computer generated) gait data corresponding to a nominal experimental gait motion. In general, joint but not inertial parameter values could be found accurately from noisy kinematic data. Root-mean-square (RMS) errors were 3° and 4 mm for joint parameter values and 1 kg, 22 mm, and 74,500 kg*mm2 for inertial parameter values. Furthermore, errors in joint but not inertial parameter values had a significant effect on calculated lower-extremity inverse dynamics joint torques. The worst RMS torque error averaged 4% bodyweight*height (BW*H) due to joint parameter variations but less than 0.25% BW*H due to inertial parameter variations. These results suggest that inverse dynamics analyses of gait utilizing linkage models with joint constraints should calibrate the model’s joint parameter values to obtain accurate joint

  19. On signals of phase transitions in salmon population dynamics.

    PubMed

    Krkošek, Martin; Drake, John M

    2014-06-01

    Critical slowing down (CSD) reflects the decline in resilience of equilibria near a bifurcation and may reveal early warning signals (EWS) of ecological phase transitions. We studied CSD in the recruitment dynamics of 120 stocks of three Pacific salmon (Oncorhynchus spp.) species in relation to critical transitions in fishery models. Pink salmon (Oncorhynchus gorbuscha) exhibited increased variability and autocorrelation in populations that had a growth parameter, r, close to zero, consistent with EWS of extinction. However, models and data for sockeye salmon (Oncorhynchus nerka) indicate that portfolio effects from heterogeneity in age-at-maturity may obscure EWS. Chum salmon (Oncorhynchus keta) show intermediate results. The data do not reveal EWS of Ricker-type bifurcations that cause oscillations and chaos at high r. These results not only provide empirical support for CSD in some ecological systems, but also indicate that portfolio effects of age structure may conceal EWS of some critical transitions. PMID:24759855

  20. Nuclear proton dynamics and interactions with calcium signaling.

    PubMed

    Hulikova, Alzbeta; Swietach, Pawel

    2016-07-01

    Biochemical signals acting on the nucleus can regulate gene expression. Despite the inherent affinity of nucleic acids and nuclear proteins (e.g. transcription factors) for protons, little is known about the mechanisms that regulate nuclear pH (pHnuc), and how these could be exploited to control gene expression. Here, we show that pHnuc dynamics can be imaged using the DNA-binding dye Hoechst 33342. Nuclear pores allow the passage of medium-sized molecules (calcein), but protons must first bind to mobile buffers in order to gain access to the nucleoplasm. Fixed buffering residing in the nucleus of permeabilized cells was estimated to be very weak on the basis of the large amplitude of pHnuc transients evoked by photolytic H(+)-uncaging or exposure to weak acids/bases. Consequently, the majority of nuclear pH buffering is sourced from the cytoplasm in the form of mobile buffers. Effective proton diffusion was faster in nucleoplasm than in cytoplasm, in agreement with the higher mobile-to-fixed buffering ratio in the nucleus. Cardiac myocyte pHnuc changed in response to maneuvers that alter nuclear Ca(2+) signals. Blocking Ca(2+) release from inositol-1,4,5-trisphosphate receptors stably alkalinized the nucleus. This Ca(2+)-pH interaction may arise from competitive binding to common chemical moieties. Competitive binding to mobile buffers may couple the efflux of Ca(2+)via nuclear pores with a counterflux of protons. This would generate a stable pH gradient between cytoplasm and nucleus that is sensitive to the state of nuclear Ca(2+) signaling. The unusual behavior of protons in the nucleus provides new mechanisms for regulating cardiac nuclear biology. PMID:26183898

  1. Dynamic conformal arc therapy: transmitted signal in vivo dosimetry.

    PubMed

    Piermattei, Angelo; Stimato, Gerardina; Gaudino, Diego; Ramella, Sara; D'Angelillo, Rolando Maria; Cellini, Francesco; Trodella, Lucio; D'Onofrio, Guido; Grimaldi, Luca; Cilla, Savino; Fidanzio, Andrea; Placidi, Elisa; Azario, Luigi

    2008-05-01

    A method for the determination of the in vivo isocenter dose, D(iso), has been applied to the dynamic conformal are therapy (DCAT) for thoracic tumors. The method makes use of the transmitted signal, S(t,alpha), measured at different gantry angles, a, by a small ion chamber positioned on the electronic portal imaging device. The in vivo method is implemented by a set of correlation functions obtained by the ratios between the transmitted signal and the midplane dose in a solid phantom, irradiated by static fields. The in vivo dosimetry at the isocenter for the DCAT requires the convolution between the signals, S(t,alpha), and the dose reconstruction factors, C(alpha), that depend on the patient's anatomy and on its tissue inhomogeneities along the beam central axis in the a direction. The C(alpha) factors are obtained by processing the patient's computed tomography scan. The method was tested by taking measurements in a cylindrical phantom and in a Rando Alderson phantom. The results show that the difference between the convolution calculations and the phantom measurements is within +/-2%. The in vivo dosimetry of the stereotactic DCAT for six lung tumors, irradiated with three or four arcs, is reported. The isocenter dose up to 17 Gy per therapy fraction was delivered on alternating days for three fractions. The agreement obtained in this pilot study between the total in vivo dose D(iso) and the planned dose D(iso,TPS) at the isocenter is +/-4%. The method has been applied on the DCAT obtaining a more extensive monitoring of possible systematic errors, the effect of which can invalidate the current therapy which uses a few high-dose fractions. PMID:18561658

  2. Dynamic conformal arc therapy: Transmitted signal in vivo dosimetry

    SciTech Connect

    Piermattei, Angelo; Stimato, Gerardina; Gaudino, Diego; Ramella, Sara; D'Angelillo, Rolando Maria; Cellini, Francesco; Trodella, Lucio; D'Onofrio, Guido; Grimaldi, Luca; Cilla, Savino; Fidanzio, Andrea; Placidi, Elisa; Azario, Luigi

    2008-05-15

    A method for the determination of the in vivo isocenter dose, D{sub iso}, has been applied to the dynamic conformal arc therapy (DCAT) for thoracic tumors. The method makes use of the transmitted signal, S{sub t,{alpha}}, measured at different gantry angles, {alpha}, by a small ion chamber positioned on the electronic portal imaging device. The in vivo method is implemented by a set of correlation functions obtained by the ratios between the transmitted signal and the midplane dose in a solid phantom, irradiated by static fields. The in vivo dosimetry at the isocenter for the DCAT requires the convolution between the signals , S{sub t,{alpha}}, and the dose reconstruction factors, C{sub {alpha}}, that depend on the patient's anatomy and on its tissue inhomogeneities along the beam central axis in the {alpha} direction. The C{sub {alpha}} factors are obtained by processing the patient's computed tomography scan. The method was tested by taking measurements in a cylindrical phantom and in a Rando Alderson phantom. The results show that the difference between the convolution calculations and the phantom measurements is within {+-}2%. The in vivo dosimetry of the stereotactic DCAT for six lung tumors, irradiated with three or four arcs, is reported. The isocenter dose up to 17 Gy per therapy fraction was delivered on alternating days for three fractions. The agreement obtained in this pilot study between the total in vivo dose D{sub iso} and the planned dose D{sub iso,TPS} at the isocenter is {+-}4%. The method has been applied on the DCAT obtaining a more extensive monitoring of possible systematic errors, the effect of which can invalidate the current therapy which uses a few high-dose fractions.

  3. Sources of dynamic variability in NF-κB signal transduction: A mechanistic model

    PubMed Central

    Mothes, Janina; Busse, Dorothea; Kofahl, Bente; Wolf, Jana

    2015-01-01

    The transcription factor NF-κB (p65/p50) plays a central role in the coordination of cellular responses by activating the transcription of numerous target genes. The precise role of the dynamics of NF-κB signalling in regulating gene expression is still an open question. Here, we show that besides external stimulation intracellular parameters can influence the dynamics of NF-κB. By applying mathematical modelling and bifurcation analyses, we show that NF-κB is capable of exhibiting different types of dynamics in response to the same stimulus. We identified the total NF-κB concentration and the IκBα transcription rate constant as two critical parameters that modulate the dynamics and the fold change of NF-κB. Both parameters might vary as a result of cell-to-cell variability. The regulation of the IκBα transcription rate constant, e.g. by co-factors, provides the possibility of regulating the NF-κB dynamics by crosstalk. PMID:25640005

  4. Improved Protein Arrays for Quantitative Systems Analysis of the Dynamics of Signaling Pathway Interactions

    SciTech Connect

    YANG, CHIN-RANG

    2013-12-11

    Astronauts and workers in nuclear plants who repeatedly exposed to low doses of ionizing radiation (IR, <10 cGy) are likely to incur specific changes in signal transduction and gene expression in various tissues of their body. Remarkable advances in high throughput genomics and proteomics technologies enable researchers to broaden their focus from examining single gene/protein kinetics to better understanding global gene/protein expression profiling and biological pathway analyses, namely Systems Biology. An ultimate goal of systems biology is to develop dynamic mathematical models of interacting biological systems capable of simulating living systems in a computer. This Glue Grant is to complement Dr. Boothman’s existing DOE grant (No. DE-FG02-06ER64186) entitled “The IGF1/IGF-1R-MAPK-Secretory Clusterin (sCLU) Pathway: Mediator of a Low Dose IR-Inducible Bystander Effect” to develop sensitive and quantitative proteomic technology that suitable for low dose radiobiology researches. An improved version of quantitative protein array platform utilizing linear Quantum dot signaling for systematically measuring protein levels and phosphorylation states for systems biology modeling is presented. The signals are amplified by a confocal laser Quantum dot scanner resulting in ~1000-fold more sensitivity than traditional Western blots and show the good linearity that is impossible for the signals of HRP-amplification. Therefore this improved protein array technology is suitable to detect weak responses of low dose radiation. Software is developed to facilitate the quantitative readout of signaling network activities. Kinetics of EGFRvIII mutant signaling was analyzed to quantify cross-talks between EGFR and other signaling pathways.

  5. Observation of Wetland Dynamics with Global Navigation Satellite Signals Reflectometry

    NASA Astrophysics Data System (ADS)

    Zuffada, C.; Shah, R.; Nghiem, S. V.; Cardellach, E.; Chew, C. C.

    2015-12-01

    Wetland dynamics is crucial to changes in both atmospheric methane and terrestrial water storage. The Intergovernmental Panel on Climate Change's Fifth Assessment Report (IPCC AR5) highlights the role of wetlands as a key driver of methane (CH4) emission, which is more than one order of magnitude stronger than carbon dioxide as a greenhouse gas in the centennial time scale. Among the multitude of methane emission sources (hydrates, livestock, rice cultivation, freshwaters, landfills and waste, fossil fuels, biomass burning, termites, geological sources, and soil oxidation), wetlands constitute the largest contributor with the widest uncertainty range of 177-284 Tg(CH4) yr-1 according to the IPCC estimate. Wetlands are highly susceptible to climate change that might lead to wetland collapse. Such wetland destruction would decrease the terrestrial water storage capacity and thus contribute to sea level rise, consequently exacerbating coastal flooding problems. For both methane change and water storage change, wetland dynamics is a crucial factor with the largest uncertainty. Nevertheless, a complete and consistent map of global wetlands still needs to be obtained as the Ramsar Convention calls for a wetlands inventory and impact assessment. We develop a new method for observations of wetland change using Global Navigation Satellite Signals Reflectometry (GNSS-R) signatures for global wetland mapping in synergy with the existing capability, not only as a static inventory but also as a temporal dataset, to advance the capability for monitoring the dynamics of wetland extent relevant to addressing the science issues of CH4 emission change and terrestrial water storage change. We will demonstrate the capability of the new GNSS-R method over a rice field in the Ebro Delta wetland in Spain.

  6. Performing dynamic time history analyses by extension of the response spectrum method

    SciTech Connect

    Hulbert, G.M.

    1983-01-01

    A method is presented to calculate the dynamic time history response of finite-element models using results from response spectrum analyses. The proposed modified time history method does not represent a new mathamatical approach to dynamic analysis but suggests a more efficient ordering of the analytical equations and procedures. The modified time history method is considerably faster and less expensive to use than normal time hisory methods. This paper presents the theory and implementation of the modified time history approach along with comparisons of the modified and normal time history methods for a prototypic seismic piping design problem.

  7. Assessment of Tools and Data for System-Level Dynamic Analyses

    SciTech Connect

    Steven J. Piet; Nick R. Soelberg

    2011-06-01

    The only fuel cycle for which dynamic analyses and assessments are not needed is the null fuel cycle - no nuclear power. For every other concept, dynamic analyses are needed and can influence relative desirability of options. Dynamic analyses show how a fuel cycle might work during transitions from today's partial fuel cycle to something more complete, impact of technology deployments, location of choke points, the key time lags, when benefits can manifest, and how well parts of fuel cycles work together. This report summarizes the readiness of existing Fuel Cycle Technology (FCT) tools and data for conducting dynamic analyses on the range of options. VISION is the primary dynamic analysis tool. Not only does it model mass flows, as do other dynamic system analysis models, but it allows users to explore various potential constraints. The only fuel cycle for which constraints are not important are those in concept advocates PowerPoint presentations; in contrast, comparative analyses of fuel cycles must address what constraints exist and how they could impact performance. The most immediate tool need is extending VISION to the thorium/U233 fuel cycle. Depending on further clarification of waste management strategies in general and for specific fuel cycle candidates, waste management sub-models in VISION may need enhancement, e.g., more on 'co-flows' of non-fuel materials, constraints in waste streams, or automatic classification of waste streams on the basis of user-specified rules. VISION originally had an economic sub-model. The economic calculations were deemed unnecessary in later versions so it was retired. Eventually, the program will need to restore and improve the economics sub-model of VISION to at least the cash flow stage and possibly to incorporating cost constraints and feedbacks. There are multiple sources of data that dynamic analyses can draw on. In this report, 'data' means experimental data, data from more detailed theoretical or empirical

  8. Comparative survey of dynamic analyses of free-piston stirling engines

    SciTech Connect

    Kankam, M.D.; Rauch, J.S.

    1994-09-01

    This paper compares reported dynamic analyses for evaluating the steady-state response and stability of free-piston Stirling engine (FPSE) systems. Various analytical approaches are discussed to provide guidance on their salient features. Recommendations are made in the recommendations remarks for an approach which captures most of the inherent properties of the engine. Such an approach has the potential for yielding results which will closely match practical FPSE-load systems.

  9. Comparative survey of dynamic analyses of free-piston Stirling engines

    NASA Technical Reports Server (NTRS)

    Kankam, M. David; Rauch, Jeffrey S.

    1991-01-01

    Reported dynamics analyses for evaluating the steady-state response and stability of free-piston Stirling engine (FPSE) systems are compared. Various analytical approaches are discussed to provide guidance on their salient features. Recommendations are made in the recommendations remarks for an approach which captures most of the inherent properties of the engine. Such an approach has the potential for yielding results which will closely match practical FPSE-load systems.

  10. Use of operational analyses to study the dynamics of troposphere-stratosphere interactions in polar regions

    NASA Technical Reports Server (NTRS)

    Salstein, David A.; Rosen, Richard D.; Miller, Alvin J.

    1988-01-01

    Operational analyses produced by large weather centers have been used in the past to monitor various aspects of the general circulation as well as address dynamical questions. For a number years researchers have been monitoring National Meteorological Center (NMC) analyses at 100 millibars because it is the level from which stratospheric analyses are built. In particular, they closely examined the pressure-work term at that level which is an important parameter related to the forcing of the stratosphere by the troposphere. Rapid fluctuations typically seen in this quanity during the months of July-November, and similarly noted by Randel et al., (1987) may raise some concern about the quality of the analyses. Researchers investigated the behavior of the term mainly responsible for these variations, namely the eddy flux of heat, and furthermore have corroborated the presence of these variations in contemporaneous analyses produced by the European Centre for Medium Range Forecasts (ECMWF). Researchers demonstrated that fluctuations in standing eddy heat fluxes, related to the forcing of the stratosphere by the troposphere, agree in two largely independent meteorological analyses. Researchers believe, that these fluctuations are mostly real.

  11. Investigating dynamics of inhibitory and feedback loops in ERK signalling using power-law models.

    PubMed

    Vera, Julio; Rath, Oliver; Balsa-Canto, Eva; Banga, Julio R; Kolch, Walter; Wolkenhauer, Olaf

    2010-11-01

    The investigation of the structure and dynamics of signal transduction systems through data-based mathematical models in ordinary differential equations or other paradigms has proven to be a successful approach in recent times. Extending this concept, we here analysed the use of kinetic models based on power-law terms with non-integer kinetic orders in the validation of hypotheses concerning regulatory structures in signalling systems. We integrated pre-existent biological knowledge, hypotheses and experimental quantitative data into a power-law model to validate the existence of certain regulatory loops in the Ras/Raf-1/MEK/ERK pathway, a MAPK pathway involved in the transduction of mitogenic and differentiation signals. Towards this end, samples of a human mammary epithelial cell line (MCF-10A) were used to obtain time-series data, characterising the behaviour of the system after epidermal growth factor stimulation in different scenarios of expression for the critical players of the system regarding the investigated loops (e.g., the inhibitory protein RKIP). The mathematical model was calibrated using a computational procedure that included: analysis of structural identifiability, global ranking of parameters to detect the most sensitivity ones towards the experimental setup, model calibration using global optimization methods to find the parameter values that better fit the data, and practical identifiability analysis to estimate the confidence in the estimated values for the parameters. The obtained model was used to perform computational simulations concerning the role of the investigated regulatory loops in the time response of the signalling pathway. Our findings suggest that the special regularity in the structure of the power-law terms make them suitable for a data-based validation of regulatory loops in signalling pathways. The model-based analysis performed identified RKIP as an actual inhibitor of the activation of the ERK pathway, but also suggested

  12. Static and dynamic stress analyses of the prototype high head Francis runner based on site measurement

    NASA Astrophysics Data System (ADS)

    Huang, X.; Oram, C.; Sick, M.

    2014-03-01

    More efforts are put on hydro-power to balance voltage and frequency within seconds for primary control in modern smart grids. This requires hydraulic turbines to run at off-design conditions. especially at low load or speed-no load. Besides. the tendency of increasing power output and decreasing weight of the turbine runners has also led to the high level vibration problem of the runners. especially high head Francis runners. Therefore. it is important to carry out the static and dynamic stress analyses of prototype high head Francis runners. This paper investigates the static and dynamic stresses on the prototype high head Francis runner based on site measurements and numerical simulations. The site measurements are performed with pressure transducers and strain gauges. Based on the measured results. computational fluid dynamics (CFD) simulations for the flow channel from stay vane to draft tube cone are performed. Static pressure distributions and dynamic pressure pulsations caused by rotor-stator interaction (RSI) are obtained under various operating conditions. With the CFD results. static and dynamic stresses on the runner at different operating points are calculated by means of the finite element method (FEM). The agreement between simulation and measurement is analysed with linear regression method. which indicates that the numerical result agrees well with that of measurement. Furthermore. the maximum static and dynamic stresses on the runner blade are obtained at various operating points. The relations of the maximum stresses and the power output are discussed in detail. The influences of the boundary conditions on the structural behaviour of the runner are also discussed.

  13. Signal-Detection Analyses of Conditional Discrimination and Delayed Matching-to-Sample Performance

    ERIC Educational Resources Information Center

    Alsop, Brent

    2004-01-01

    Quantitative analyses of stimulus control and reinforcer control in conditional discriminations and delayed matching-to-sample procedures often encounter a problem; it is not clear how to analyze data when subjects have not made errors. The present article examines two common methods for overcoming this problem. Monte Carlo simulations of…

  14. Cell cycle dynamics in a response/signalling feedback system with a gap

    PubMed Central

    Gong, Xue; Buckalew, Richard; Young, Todd; Boczko, Erik

    2014-01-01

    We consider a dynamical model of cell cycles of n cells in a culture in which cells in one specific phase (S for signalling) of the cell cycle produce chemical agents that influence the growth/cell cycle progression of cells in another phase (R for responsive). In the case that the feedback is negative, it is known that subpopulations of cells tend to become clustered in the cell cycle; while for a positive feedback, all the cells tend to become synchronized. In this paper, we suppose that there is a gap between the two phases. The gap can be thought of as modelling the physical reality of a time delay in the production and action of the signalling agents. We completely analyse the dynamics of this system when the cells are arranged into two cell cycle clusters. We also consider the stability of certain important periodic solutions in which clusters of cells have a cyclic arrangement and there are just enough clusters to allow interactions between them. We find that the inclusion of a small gap does not greatly alter the global dynamics of the system; there are still large open sets of parameters for which clustered solutions are stable. Thus, we add to the evidence that clustering can be a robust phenomenon in biological systems. However, the gap does effect the system by enhancing the stability of the stable clustered solutions. We explain this phenomenon in terms of contraction rates (Floquet exponents) in various invariant subspaces of the system. We conclude that in systems for which these models are reasonable, a delay in signalling is advantageous to the emergence of clustering. PMID:24963979

  15. Interaction between telencephalic signals and respiratory dynamics in songbirds

    PubMed Central

    Méndez, Jorge M.; Mindlin, Gabriel B.

    2012-01-01

    The mechanisms by which telencephalic areas affect motor activities are largely unknown. They could either take over motor control from downstream motor circuits or interact with the intrinsic dynamics of these circuits. Both models have been proposed for telencephalic control of respiration during learned vocal behavior in birds. The interactive model postulates that simple signals from the telencephalic song control areas are sufficient to drive the nonlinear respiratory network into producing complex temporal sequences. We tested this basic assumption by electrically stimulating telencephalic song control areas and analyzing the resulting respiratory patterns in zebra finches and in canaries. We found strong evidence for interaction between the rhythm of stimulation and the intrinsic respiratory rhythm, including naturally emerging subharmonic behavior and integration of lateralized telencephalic input. The evidence for clear interaction in our experimental paradigm suggests that telencephalic vocal control also uses a similar mechanism. Furthermore, species differences in the response of the respiratory system to stimulation show parallels to differences in the respiratory patterns of song, suggesting that the interactive production of respiratory rhythms is manifested in species-specific specialization of the involved circuitry. PMID:22402649

  16. Variational Assimilation of Global Microwave Rainfall Retrievals: Physical and Dynamical Impact on GEOS Analyses and Forecasts

    NASA Technical Reports Server (NTRS)

    Lin, Xin; Zhang, Sara Q.; Hou, Arthur Y.

    2006-01-01

    Global microwave rainfall retrievals from a 5-satellite constellation, including TMI from TRMM, SSWI from DMSP F13, F14 and F15, and AMSR-E from EOS-AQUA, are assimilated into the NASA Goddard Earth Observing System (GEOS) Data Assimilation System (DAS) using a 1-D variational continuous assimilation (VCA) algorithm. The physical and dynamical impact of rainfall assimilation on GEOS analyses and forecasts is examined at various temporal and spatial scales. This study demonstrates that the 1-D VCA algorithm, which was originally developed and evaluated for rainfall assimilations over tropical oceans, can effectively assimilate satellite microwave rainfall retrievals and improve GEOS analyses over both the Tropics and the extratropics where the atmospheric processes are dominated by different large-scale dynamics and moist physics, and also over the land, where rainfall estimates from passive microwave radiometers are believed to be less accurate. Results show that rainfall assimilation renders the GEOS analysis physically and dynamically more consistent with the observed precipitation at the monthly-mean and 6-hour time scales. Over regions where the model precipitation tends to misbehave in distinctly different rainy regimes, the 1-D VCA algorithm, by compensating for errors in the model s moist time-tendency in a 6-h analysis window, is able to bring the rainfall analysis closer to the observed. The radiation and cloud fields also tend to be in better agreement with independent satellite observations in the rainfall-assimilation m especially over regions where rainfall analyses indicate large improvements. Assimilation experiments with and without rainfall data for a midlatitude frontal system clearly indicates that the GEOS analysis is improved through changes in the thermodynamic and dynamic fields that respond to the rainfall assimilation. The synoptic structures of temperature, moisture, winds, divergence, and vertical motion, as well as vorticity are more

  17. Development of microbial-enzyme-mediated decomposition model parameters through steady-state and dynamic analyses

    SciTech Connect

    Wang, Gangsheng; Post, Wilfred M; Mayes, Melanie

    2013-01-01

    We developed a Microbial-ENzyme-mediated Decomposition (MEND) model, based on the Michaelis-Menten kinetics, that describes the dynamics of physically defined pools of soil organic matter (SOC). These include particulate, mineral-associated, dissolved organic matter (POC, MOC, and DOC, respectively), microbial biomass, and associated exoenzymes. The ranges and/or distributions of parameters were determined by both analytical steady-state and dynamic analyses with SOC data from the literature. We used an improved multi-objective parameter sensitivity analysis (MOPSA) to identify the most important parameters for the full model: maintenance of microbial biomass, turnover and synthesis of enzymes, and carbon use efficiency (CUE). The model predicted an increase of 2 C (baseline temperature =12 C) caused the pools of POC-Cellulose, MOC, and total SOC to increase with dynamic CUE and decrease with constant CUE, as indicated by the 50% confidence intervals. Regardless of dynamic or constant CUE, the pool sizes of POC, MOC, and total SOC varied from 8% to 8% under +2 C. The scenario analysis using a single parameter set indicates that higher temperature with dynamic CUE might result in greater net increases in both POC-Cellulose and MOC pools. Different dynamics of various SOC pools reflected the catalytic functions of specific enzymes targeting specific substrates and the interactions between microbes, enzymes, and SOC. With the feasible parameter values estimated in this study, models incorporating fundamental principles of microbial-enzyme dynamics can lead to simulation results qualitatively different from traditional models with fast/slow/passive pools.

  18. Expression and functional analyses of the Arabidopsis QUA1 gene in light signal transduction.

    PubMed

    Zhaojin, Chen; Chuanyu, Ding; Yuan, Zheng

    2016-05-01

    Plants not only use light as an energy source for photosynthesis, but also have to monitor the light quality and quantity input to execute appropriate physiological and developmental responses, such as cell differentiation, structural and functional changes, as well as the formation of tissues and organs. The process is referred to as photomorphogenesis. Arabidopsis QUA1 (QUASIMODO1), which functions in pectin synthesis, is identified as a member of glycosyltransferases. Previously, the hypocotyl elongation of the qua1-1 mutant was shown to be inhibited under dark conditions. In this study, we used the qua1-1/cry1 and qua1-1/phyB double mutants as the materials to study the function of the QUA1 gene in light signal transduction. The results showed that QUA1 not only participated in hypocotyl elongation under dark conditions, but also in blue light, red light and far red light conditions. In qua1-1 mutant seedlings, both the cell length of hypocotyl and the light-regulated gene expression were affected. Compared with cry1 and phyB mutants, qua1-1/cry1 and qua1-1/phyB double mutants had the shorter hypocotyl. Light-regulated gene expression was also affected in the double mutants. These data indicated that QUA1 might participate in the light signal transduction regulated by CRY1 and PHYB. Hence, the QUA1 gene may play multiple roles in light signal transduction by regulating the cell elongation and light-regulated gene expression. PMID:27232492

  19. The importance of replicating genomic analyses to verify phylogenetic signal for recently evolved lineages.

    PubMed

    Fraser, Ceridwen I; McGaughran, Angela; Chuah, Aaron; Waters, Jonathan M

    2016-08-01

    Genomewide SNP data generated by nontargeted methods such as RAD and GBS are increasingly being used in phylogenetic and phylogeographic analyses. When these methods are used in the absence of a reference genome, however, little is known about the locations and evolution of the SNPs. In using such data to address phylogenetic questions, researchers risk drawing false conclusions, particularly if a representative number of SNPs is not obtained. Here, we empirically test the robustness of phylogenetic inference based on SNP data for closely related lineages. We conducted a genomewide analysis of 75 712 SNPs, generated via GBS, of southern bull-kelp (Durvillaea). Durvillaea chathamensis co-occurs with D. antarctica on Chatham Island, but the two species have previously been found to be so genetically similar that the status of the former has been questioned. Our results show that D. chathamensis, which differs from D. antarctica ecologically as well as morphologically, is indeed a reproductively isolated species. Furthermore, our replicated analyses show that D. chathamensis cannot be reliably distinguished phylogenetically from closely related D. antarctica using subsets (ranging in size from 400 to 10 000 sites) of the 40 912 parsimony-informative SNPs in our data set and that bootstrap values alone can give misleading impressions of the strength of phylogenetic inferences. These results highlight the importance of independently replicating SNP analyses to verify that phylogenetic inferences based on nontargeted SNP data are robust. Our study also demonstrates that modern genomic approaches can be used to identify cases of recent or incipient speciation that traditional approaches (e.g. Sanger sequencing of a few loci) may be unable to detect or resolve. PMID:27238591

  20. Prediction of Seismic Slope Displacements by Dynamic Stick-Slip Analyses

    SciTech Connect

    Ausilio, Ernesto; Costanzo, Antonio; Silvestri, Francesco; Tropeano, Giuseppe

    2008-07-08

    A good-working balance between simplicity and reliability in assessing seismic slope stability is represented by displacement-based methods, in which the effects of deformability and ductility can be either decoupled or coupled in the dynamic analyses. In this paper, a 1D lumped mass 'stick-slip' model is developed, accounting for soil heterogeneity and non-linear behaviour, with a base sliding mechanism at a potential rupture surface. The results of the preliminary calibration show a good agreement with frequency-domain site response analysis in no-slip conditions. The comparison with rigid sliding block analyses and with the decoupled approach proves that the stick-slip procedure can result increasingly unconservative for soft soils and deep sliding depths.

  1. Static and dynamic theoretical analyses of a scanning tip on suspended graphene surface

    NASA Astrophysics Data System (ADS)

    Yu, Yan-Zi; Guo, Jian-Gang

    2016-08-01

    Recent research progress shows that graphene exhibits distinct adhesion and friction behaviors. In the paper, the static and dynamic analyses of a diamond tip sliding on suspended graphene surface are conducted via theoretical and numerical research methods, and the adhesion and friction properties between them are investigated. The analytical expression of interaction potential between a diamond tip and graphene surface is derived based on the interatomic pairwise potential, and then, the lateral and normal interaction forces are calculated. The equilibrium heights and adhesion energy of the diamond tip are calculated on three particular sites of graphene surface. The influence of vertical distance between the tip and graphene surface is studied on the maximum static frictional force and initial velocity of tip. What is more, the influence of scanning velocity and damping are also analyzed on the frictional force and dynamic behaviors of the scanning tip, and the "stick-slip" phenomenon is observed and discussed by the numerical calculation.

  2. Comparing of Normal Stress Distribution in Static and Dynamic Soil-Structure Interaction Analyses

    NASA Astrophysics Data System (ADS)

    Kholdebarin, Alireza; Massumi, Ali; Davoodi, Mohammad; Tabatabaiefar, Hamid Reza

    2008-07-01

    It is important to consider the vertical component of earthquake loading and inertia force in soil-structure interaction analyses. In most circumstances, design engineers are primarily concerned about the analysis of behavior of foundations subjected to earthquake-induced forces transmitted from the bedrock. In this research, a single rigid foundation with designated geometrical parameters located on sandy-clay soil has been modeled in FLAC software with Finite Different Method and subjected to three different vertical components of earthquake records. In these cases, it is important to evaluate effect of footing on underlying soil and to consider normal stress in soil with and without footing. The distribution of normal stress under the footing in static and dynamic states has been studied and compared. This Comparison indicated that, increasing in normal stress under the footing caused by vertical component of ground excitations, has decreased dynamic vertical settlement in comparison with static state.

  3. Comparing of Normal Stress Distribution in Static and Dynamic Soil-Structure Interaction Analyses

    SciTech Connect

    Kholdebarin, Alireza; Massumi, Ali; Davoodi, Mohammad; Tabatabaiefar, Hamid Reza

    2008-07-08

    It is important to consider the vertical component of earthquake loading and inertia force in soil-structure interaction analyses. In most circumstances, design engineers are primarily concerned about the analysis of behavior of foundations subjected to earthquake-induced forces transmitted from the bedrock. In this research, a single rigid foundation with designated geometrical parameters located on sandy-clay soil has been modeled in FLAC software with Finite Different Method and subjected to three different vertical components of earthquake records. In these cases, it is important to evaluate effect of footing on underlying soil and to consider normal stress in soil with and without footing. The distribution of normal stress under the footing in static and dynamic states has been studied and compared. This Comparison indicated that, increasing in normal stress under the footing caused by vertical component of ground excitations, has decreased dynamic vertical settlement in comparison with static state.

  4. Radiation-induced signals of gypsum crystals analysed by ESR and TL techniques applied to dating

    NASA Astrophysics Data System (ADS)

    Aydaş, Canan; Engin, Birol; Aydın, Talat

    2011-02-01

    Natural crystals of terrestrial gypsum were investigated concerning the radiation effects on Electron spin resonance (ESR) and Thermoluminescence (TL) properties and their application for geological dating. ESR signals of Fe 3+, Mn 2+, G1 ( SO3-, g = 2.003) and G2 ( SO4-, g∥=2.018g⊥=2.009) centers were observed. The thermal stability and dose response of the ESR signals were found to be suitable for an age determination using a signal at g = 2.009. The intensity of this center increased with γ-radiation and the additive dose method for this ESR center yielded accumulated dose GD of 67.4 ± 10.1 Gy. Using U, Th and K contents plus the cosmic-ray contribution, a dose rate of 1.92 ± 0.22 mGy/year has been obtained. We have determined the ESR age of the gypsums to be (35 ± 4) × 10 3 years. TL peaks at 157 and 278 °C were observed. By using initial rise method the thermal activation energy of 278 °C TL peak was found to be underestimated, probably due to the thermal quenching. Activation energies and frequency factors obtained by the method of varying the heating rate indicate lifetime of 4.09 × 10 7 years (at 15 °C) for 278 °C peak. The additive dose method applied to this TL peak yielded GD of 75 ± 11 Gy. The corresponding TL age using the 278 °C TL peak was found to be (39 ± 5) × 10 3 years for gypsum sample. The TL age of this sample is consistent with the ESR age within experimental error limits. The obtained ESR and TL ages are not consistent with the expectations of geologists. This contradiction is probably due to the repeatedly recrystallisation of gypsum samples under the environmental conditions after their formation in the upper Miocene-Pliocene Epoch.

  5. Signal enhancement in ligand-receptor interactions using dynamic polymers at quartz crystal microbalance sensors.

    PubMed

    Dunér, Gunnar; Anderson, Henrik; Pei, Zhichao; Ingemarsson, Björn; Aastrup, Teodor; Ramström, Olof

    2016-06-20

    The signal enhancement properties of QCM sensors based on dynamic, biotinylated poly(acrylic acid) brushes has been studied in interaction studies with an anti-biotin Fab fragment. The poly(acrylic acid) sensors showed a dramatic increase in signal response with more than ten times higher signal than the carboxyl-terminated self-assembled monolayer surface. PMID:27196531

  6. Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells.

    PubMed

    Luo, Yuping; Coskun, Volkan; Liang, Aibing; Yu, Juehua; Cheng, Liming; Ge, Weihong; Shi, Zhanping; Zhang, Kunshan; Li, Chun; Cui, Yaru; Lin, Haijun; Luo, Dandan; Wang, Junbang; Lin, Connie; Dai, Zachary; Zhu, Hongwen; Zhang, Jun; Liu, Jie; Liu, Hailiang; deVellis, Jean; Horvath, Steve; Sun, Yi Eve; Li, Siguang

    2015-05-21

    The scarcity of tissue-specific stem cells and the complexity of their surrounding environment have made molecular characterization of these cells particularly challenging. Through single-cell transcriptome and weighted gene co-expression network analysis (WGCNA), we uncovered molecular properties of CD133(+)/GFAP(-) ependymal (E) cells in the adult mouse forebrain neurogenic zone. Surprisingly, prominent hub genes of the gene network unique to ependymal CD133(+)/GFAP(-) quiescent cells were enriched for immune-responsive genes, as well as genes encoding receptors for angiogenic factors. Administration of vascular endothelial growth factor (VEGF) activated CD133(+) ependymal neural stem cells (NSCs), lining not only the lateral but also the fourth ventricles and, together with basic fibroblast growth factor (bFGF), elicited subsequent neural lineage differentiation and migration. This study revealed the existence of dormant ependymal NSCs throughout the ventricular surface of the CNS, as well as signals abundant after injury for their activation. PMID:26000486

  7. Ibutilide Increases the Variability and Complexity of Atrial Fibrillation Electrograms: Antiarrhythmic Insights Using Signal Analyses

    PubMed Central

    Biviano, Angelo B.; Ciaccio, Edward J.; Whang, William; Garan, Hasan

    2013-01-01

    Introduction Intravenous ibutilide is used to convert atrial fibrillation (AF) to sinus rhythm due to its Class III antiarrhythmic mechanisms. However, the effects of ibutilide on local electrograms during AF have not been elucidated. Methods and Results We used electrogram (EGM) analysis techniques to characterize how ibutilide administration changes the frequency, morphology, and repeatability of AF EGM signals, thereby providing insight into ibutilide’s antiarrhythmic mechanism of action. AF recordings were collected from 21 patients with AF both before and after ibutilide administration. The effects of ibutilide on the following AF EGM parameters were assessed: 1) dominant frequency, 2) variations in EGM amplitude and overall morphology, 3) repetition of electrogram patterns, and 4) complexity of the AF frequency spectra. When comparing pre- vs. post-ibutilide administration EGMs, DF decreased from 5.45 to 4.02 Hz (p<0.0001). There was an increase both in the variability of AF EGM amplitudes (p=0.003) and variability of overall AF EGM morphologies (p=0.003). AF EGM pattern repetitiveness decreased (p=0.01), and the AF frequency spectral profile manifested greater complexity (p=0.02). Conclusions Novel electrogram signal analysis techniques reveal that ibutilide administration causes increased complexity in the atrial electrical activation pattern while decreasing rate. These findings may be explained by the progressive destabilization of higher frequency, more homogeneous primary drivers of AF over the course of ibutilide administration and/or less uniform propagation of atrial activation, until AF maintenance becomes more difficult and either transforms to atrial tachycardia or terminates to sinus rhythm. PMID:23875908

  8. Combination of transcriptomic and metabolomic analyses reveals a JAZ repressor in the jasmonate signaling pathway of Salvia miltiorrhiza

    PubMed Central

    Ge, Qian; Zhang, Yuan; Hua, Wen-Ping; Wu, Yu-Cui; Jin, Xin-Xin; Song, Shuang-Hong; Wang, Zhe-Zhi

    2015-01-01

    Jasmonates (JAs) are plant-specific key signaling molecules that respond to various stimuli and are involved in the synthesis of secondary metabolites. However, little is known about the JA signal pathway, especially in economically significant medicinal plants. To determine the functions of novel genes that participate in the JA-mediated accumulation of secondary metabolites, we examined the metabolomic and transcriptomic signatures from Salvia miltiorrhiza. For the metabolome, 35 representative metabolites showing significant changes in rates of accumulation were extracted and identified. We also screened out 2131 differentially expressed unigenes, of which 30 were involeved in the phenolic secondary metabolic pathway, while 25 were in the JA biosynthesis and signal pathways. Among several MeJA-induced novel genes, SmJAZ8 was selected for detailed functional analysis. Transgenic plants over-expressing SmJAZ8 exhibited a JA-insensitive phenotype, suggesting that the gene is a transcriptional regulator in the JA signal pathway of S. miltiorrhiza. Furthermore, this transgenic tool revealed that JAZ genes have novel function in the constitutive accumulation of secondary metabolites. Based on these findings, we propose that the combined strategy of transcriptomic and metabolomic analyses is valuable for efficient discovery of novel genes in plants. PMID:26388160

  9. Deep sequencing and in silico analyses identify MYB-regulated gene networks and signaling pathways in pancreatic cancer

    PubMed Central

    Azim, Shafquat; Zubair, Haseeb; Srivastava, Sanjeev K.; Bhardwaj, Arun; Zubair, Asif; Ahmad, Aamir; Singh, Seema; Khushman, Moh’d.; Singh, Ajay P.

    2016-01-01

    We have recently demonstrated that the transcription factor MYB can modulate several cancer-associated phenotypes in pancreatic cancer. In order to understand the molecular basis of these MYB-associated changes, we conducted deep-sequencing of transcriptome of MYB-overexpressing and -silenced pancreatic cancer cells, followed by in silico pathway analysis. We identified significant modulation of 774 genes upon MYB-silencing (p < 0.05) that were assigned to 25 gene networks by in silico analysis. Further analyses placed genes in our RNA sequencing-generated dataset to several canonical signalling pathways, such as cell-cycle control, DNA-damage and -repair responses, p53 and HIF1α. Importantly, we observed downregulation of the pancreatic adenocarcinoma signaling pathway in MYB-silenced pancreatic cancer cells exhibiting suppression of EGFR and NF-κB. Decreased expression of EGFR and RELA was validated by both qPCR and immunoblotting and they were both shown to be under direct transcriptional control of MYB. These observations were further confirmed in a converse approach wherein MYB was overexpressed ectopically in a MYB-null pancreatic cancer cell line. Our findings thus suggest that MYB potentially regulates growth and genomic stability of pancreatic cancer cells via targeting complex gene networks and signaling pathways. Further in-depth functional studies are warranted to fully understand MYB signaling in pancreatic cancer. PMID:27354262

  10. Deep sequencing and in silico analyses identify MYB-regulated gene networks and signaling pathways in pancreatic cancer.

    PubMed

    Azim, Shafquat; Zubair, Haseeb; Srivastava, Sanjeev K; Bhardwaj, Arun; Zubair, Asif; Ahmad, Aamir; Singh, Seema; Khushman, Moh'd; Singh, Ajay P

    2016-01-01

    We have recently demonstrated that the transcription factor MYB can modulate several cancer-associated phenotypes in pancreatic cancer. In order to understand the molecular basis of these MYB-associated changes, we conducted deep-sequencing of transcriptome of MYB-overexpressing and -silenced pancreatic cancer cells, followed by in silico pathway analysis. We identified significant modulation of 774 genes upon MYB-silencing (p < 0.05) that were assigned to 25 gene networks by in silico analysis. Further analyses placed genes in our RNA sequencing-generated dataset to several canonical signalling pathways, such as cell-cycle control, DNA-damage and -repair responses, p53 and HIF1α. Importantly, we observed downregulation of the pancreatic adenocarcinoma signaling pathway in MYB-silenced pancreatic cancer cells exhibiting suppression of EGFR and NF-κB. Decreased expression of EGFR and RELA was validated by both qPCR and immunoblotting and they were both shown to be under direct transcriptional control of MYB. These observations were further confirmed in a converse approach wherein MYB was overexpressed ectopically in a MYB-null pancreatic cancer cell line. Our findings thus suggest that MYB potentially regulates growth and genomic stability of pancreatic cancer cells via targeting complex gene networks and signaling pathways. Further in-depth functional studies are warranted to fully understand MYB signaling in pancreatic cancer. PMID:27354262

  11. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

    PubMed

    Day, Felix R; Ruth, Katherine S; Thompson, Deborah J; Lunetta, Kathryn L; Pervjakova, Natalia; Chasman, Daniel I; Stolk, Lisette; Finucane, Hilary K; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D; Elks, Cathy E; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A; Franke, Lude L; Huffman, Jennifer E; Keller, Margaux F; McArdle, Patrick F; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M; Schick, Ursula M; Smith, Jennifer A; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V; Tanaka, Toshiko; Abecasis, Gonçalo R; Andrulis, Irene L; Anton-Culver, Hoda; Antoniou, Antonis C; Arndt, Volker; Arnold, Alice M; Barbieri, Caterina; Beckmann, Matthias W; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J; Chapman, J Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J; Coviello, Andrea D; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dunning, Alison M; Eicher, John D; Fasching, Peter A; Faul, Jessica D; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E; García-Closas, Montserrat; Giles, Graham G; Girotto, Giorgia G; Goldberg, Mark S; González-Neira, Anna; Goodarzi, Mark O; Grove, Megan L; Gudbjartsson, Daniel F; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A; Hall, Per; Hamann, Ute; Henderson, Brian E; Hocking, Lynne J; Hofman, Albert; Homuth, Georg; Hooning, Maartje J; Hopper, John L; Hu, Frank B; Huang, Jinyan; Humphreys, Keith; Hunter, David J; Jakubowska, Anna; Jones, Samuel E; Kabisch, Maria; Karasik, David; Knight, Julia A; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian'an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Benjamin M; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B; Nordestgaard, Børge G; Olson, Janet E; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D P; Pirastu, Nicola N; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F; Sanna, Serena; Sawyer, Elinor J; Schlessinger, David; Schmidt, Marjanka K; Schmidt, Frank; Schmutzler, Rita K; Schoemaker, Minouk J; Scott, Robert A; Seynaeve, Caroline M; Simard, Jacques; Sorice, Rossella; Southey, Melissa C; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D; Thorsteinsdottir, Unnur; Toland, Amanda E; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F; Winqvist, Robert; Wolffenbuttel, Bruce B H R; Wright, Alan F; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I; Buring, Julie E; Ferrucci, Luigi; Montgomery, Grant W; Gudnason, Vilmundur; Spector, Tim D; van Duijn, Cornelia M; Alizadeh, Behrooz Z; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F; Gasparini, Paolo P; Gieger, Christian; Harris, Tamara B; Hayward, Caroline; Kardia, Sharon L R; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C; Reiner, Alex P; Ridker, Paul M; Rotter, Jerome I; Toniolo, Daniela; Uitterlinden, André G; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J; Weir, David R; Yerges-Armstrong, Laura M; Price, Alkes L; Stefansson, Kari; Visser, Jenny A; Ong, Ken K; Chang-Claude, Jenny; Murabito, Joanne M; Perry, John R B; Murray, Anna

    2015-11-01

    Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms. PMID:26414677

  12. Large-scale genomic analyses link reproductive ageing to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair

    PubMed Central

    Lunetta, Kathryn L.; Pervjakova, Natalia; Chasman, Daniel I.; Stolk, Lisette; Finucane, Hilary K.; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D.; Elks, Cathy E.; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A.; Franke, Lude L.; Huffman, Jennifer E.; Keller, Margaux F.; McArdle, Patrick F.; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M.; Schick, Ursula M.; Smith, Jennifer A.; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V.; Tanaka, Toshiko; Abecasis, Goncalo; Andrulis, Irene L.; Anton-Culver, Hoda; Antoniou, Antonis C.; Arndt, Volker; Arnold, Alice M.; Barbieri, Caterina; Beckmann, Matthias W.; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J.; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J.; Chapman, J. Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J.; Coviello, Andrea D.; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W.; Dennis, Joe; Devilee, Peter; Dörk, Thilo; dos-Santos-Silva, Isabel; Dunning, Alison M.; Eicher, John D.; Fasching, Peter A.; Faul, Jessica D.; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E.; García-Closas, Montserrat; Giles, Graham G.; Girotto, Giorgia G.; Goldberg, Mark S.; González-Neira, Anna; Goodarzi, Mark O.; Grove, Megan L.; Gudbjartsson, Daniel F.; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A.; Hall, Per; Hamann, Ute; Henderson, Brian E.; Hocking, Lynne J.; Hofman, Albert; Homuth, Georg; Hooning, Maartje J.; Hopper, John L.; Hu, Frank B.; Huang, Jinyan; Humphreys, Keith; Hunter, David J.; Jakubowska, Anna; Jones, Samuel E.; Kabisch, Maria; Karasik, David; Knight, Julia A.; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian’an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G.; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L.; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Ben M.; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B.; Nordestgaard, Børge G.; Olson, Janet E.; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D.P.; Pirastu, Nicola N.; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M.; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J.; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F.; Sanna, Serena; Sawyer, Elinor J.; Schlessinger, David; Schmidt, Marjanka K.; Schmidt, Frank; Schmutzler, Rita K.; Schoemaker, Minouk J.; Scott, Robert A.; Seynaeve, Caroline M.; Simard, Jacques; Sorice, Rossella; Southey, Melissa C.; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D.; Thorsteinsdottir, Unnur; Toland, Amanda E.; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T.; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F.; Winqvist, Robert; Wolffenbuttel, Bruce B.H.R.; Wright, Alan F.; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I.; Buring, Julie E.; Ferrucci, Luigi; Montgomery, Grant W.; Gudnason, Vilmundur; Spector, Tim D.; van Duijn, Cornelia M; Alizadeh, Behrooz Z.; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F.; Gasparini, Paolo P.; Gieger, Christian; Harris, Tamara B.; Hayward, Caroline; Kardia, Sharon L.R.; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C.; Reiner, Alex P.; Ridker, Paul M.; Rotter, Jerome I.; Toniolo, Daniela; Uitterlinden, André G.; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J.; Weir, David R.; Yerges-Armstrong, Laura M.; Price, Alkes L.; Stefansson, Kari; Visser, Jenny A.; Ong, Ken K.; Chang-Claude, Jenny; Murabito, Joanne M.; Perry, John R.B.; Murray, Anna

    2015-01-01

    Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ~70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two harbouring additional rare missense alleles of large effect. We found enrichment of signals in/near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses revealed a major association with DNA damage-response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomisation analyses supported a causal effect of later ANM on breast cancer risk (~6% risk increase per-year, P=3×10−14), likely mediated by prolonged sex hormone exposure, rather than DDR mechanisms. PMID:26414677

  13. Analysing calcium signalling of cells under high shear flows using discontinuous dielectrophoresis.

    PubMed

    Soffe, Rebecca; Baratchi, Sara; Tang, Shi-Yang; Nasabi, Mahyar; McIntyre, Peter; Mitchell, Arnan; Khoshmanesh, Khashayar

    2015-01-01

    Immobilisation of cells is an important feature of many cellular assays, as it enables the physical/chemical stimulation of cells; whilst, monitoring cellular processes using microscopic techniques. Current approaches for immobilising cells, however, are hampered by time-consuming processes, the need for specific antibodies or coatings, and adverse effects on cell integrity. Here, we present a dielectrophoresis-based approach for the robust immobilisation of cells, and analysis of their responses under high shear flows. This approach is quick and label-free, and more importantly, minimises the adverse effects of electric field on the cell integrity, by activating the field for a short duration of 120 s, just long enough to immobilise the cells, after which cell culture media (such as HEPES) is flushed through the platform. In optimal conditions, at least 90% of the cells remained stably immobilised, when exposed to a shear stress of 63 dyn/cm(2). This approach was used to examine the shear-induced calcium signalling of HEK-293 cells expressing a mechanosensitive ion channel, transient receptor potential vaniloid type 4 (TRPV4), when exposed to the full physiological range of shear stress. PMID:26202725

  14. Analysing calcium signalling of cells under high shear flows using discontinuous dielectrophoresis

    NASA Astrophysics Data System (ADS)

    Soffe, Rebecca; Baratchi, Sara; Tang, Shi-Yang; Nasabi, Mahyar; McIntyre, Peter; Mitchell, Arnan; Khoshmanesh, Khashayar

    2015-07-01

    Immobilisation of cells is an important feature of many cellular assays, as it enables the physical/chemical stimulation of cells; whilst, monitoring cellular processes using microscopic techniques. Current approaches for immobilising cells, however, are hampered by time-consuming processes, the need for specific antibodies or coatings, and adverse effects on cell integrity. Here, we present a dielectrophoresis-based approach for the robust immobilisation of cells, and analysis of their responses under high shear flows. This approach is quick and label-free, and more importantly, minimises the adverse effects of electric field on the cell integrity, by activating the field for a short duration of 120 s, just long enough to immobilise the cells, after which cell culture media (such as HEPES) is flushed through the platform. In optimal conditions, at least 90% of the cells remained stably immobilised, when exposed to a shear stress of 63 dyn/cm2. This approach was used to examine the shear-induced calcium signalling of HEK-293 cells expressing a mechanosensitive ion channel, transient receptor potential vaniloid type 4 (TRPV4), when exposed to the full physiological range of shear stress.

  15. Analysing calcium signalling of cells under high shear flows using discontinuous dielectrophoresis

    PubMed Central

    Soffe, Rebecca; Baratchi, Sara; Tang, Shi-Yang; Nasabi, Mahyar; McIntyre, Peter; Mitchell, Arnan; Khoshmanesh, Khashayar

    2015-01-01

    Immobilisation of cells is an important feature of many cellular assays, as it enables the physical/chemical stimulation of cells; whilst, monitoring cellular processes using microscopic techniques. Current approaches for immobilising cells, however, are hampered by time-consuming processes, the need for specific antibodies or coatings, and adverse effects on cell integrity. Here, we present a dielectrophoresis-based approach for the robust immobilisation of cells, and analysis of their responses under high shear flows. This approach is quick and label-free, and more importantly, minimises the adverse effects of electric field on the cell integrity, by activating the field for a short duration of 120 s, just long enough to immobilise the cells, after which cell culture media (such as HEPES) is flushed through the platform. In optimal conditions, at least 90% of the cells remained stably immobilised, when exposed to a shear stress of 63 dyn/cm2. This approach was used to examine the shear-induced calcium signalling of HEK-293 cells expressing a mechanosensitive ion channel, transient receptor potential vaniloid type 4 (TRPV4), when exposed to the full physiological range of shear stress. PMID:26202725

  16. Dynamics and spatial structure of ENSO from re-analyses versus CMIP5 models

    NASA Astrophysics Data System (ADS)

    Serykh, Ilya; Sonechkin, Dmitry

    2016-04-01

    Basing on a mathematical idea about the so-called strange nonchaotic attractor (SNA) in the quasi-periodically forced dynamical systems, the currently available re-analyses data are considered. It is found that the El Niño - Southern Oscillation (ENSO) is driven not only by the seasonal heating, but also by three more external periodicities (incommensurate to the annual period) associated with the ~18.6-year lunar-solar nutation of the Earth rotation axis, ~11-year sunspot activity cycle and the ~14-month Chandler wobble in the Earth's pole motion. Because of the incommensurability of their periods all four forces affect the system in inappropriate time moments. As a result, the ENSO time series look to be very complex (strange in mathematical terms) but nonchaotic. The power spectra of ENSO indices reveal numerous peaks located at the periods that are multiples of the above periodicities as well as at their sub- and super-harmonic. In spite of the above ENSO complexity, a mutual order seems to be inherent to the ENSO time series and their spectra. This order reveals itself in the existence of a scaling of the power spectrum peaks and respective rhythms in the ENSO dynamics that look like the power spectrum and dynamics of the SNA. It means there are no limits to forecast ENSO, in principle. In practice, it opens a possibility to forecast ENSO for several years ahead. Global spatial structures of anomalies during El Niño and power spectra of ENSO indices from re-analyses are compared with the respective output quantities in the CMIP5 climate models (the Historical experiment). It is found that the models reproduce global spatial structures of the near surface temperature and sea level pressure anomalies during El Niño very similar to these fields in the re-analyses considered. But the power spectra of the ENSO indices from the CMIP5 models show no peaks at the same periods as the re-analyses power spectra. We suppose that it is possible to improve modeled

  17. Nonlinear estimation of coherent phase vibrations for statistical signals through multivariable analyses

    NASA Astrophysics Data System (ADS)

    Deng, Linhua

    2015-07-01

    Three nonlinear analysis techniques, including cross-recurrence plot, line of synchronization, and cross-wavelet transform, are proposed to estimate the coherent phase vibrations of nonlinear and non-stationary time series. The case study utilizes the monthly averages of sunspot areas during the time interval from May 1874 to August 2014. The following prominent results are found: (1) the phase-leading hemisphere of long-term sunspot areas has changed twice in the past 140 years, indicating that the hemispheric imbalances and apparent phase differences on both hemispheres are a prevalent behavior and are not anomalous; (2) the alternating regularity of hemispheric asynchronism exhibits a cyclical pattern of 4.5+3.5 cycles, and the magnetic flux excess in a certain hemisphere during the ascending branch of a cycle can be taken as an indication of the phase-leading hemisphere in this cycle. We firmly believe that powerful nonlinear approaches are more advanced than classical linear methods when they are combined to determine the dynamic complexity of nonlinear physical systems.

  18. A Dynamic Stimulus-Driven Model of Signal Detection

    ERIC Educational Resources Information Center

    Turner, Brandon M.; Van Zandt, Trisha; Brown, Scott

    2011-01-01

    Signal detection theory forms the core of many current models of cognition, including memory, choice, and categorization. However, the classic signal detection model presumes the a priori existence of fixed stimulus representations--usually Gaussian distributions--even when the observer has no experience with the task. Furthermore, the classic…

  19. Phosphoproteomic Analyses Reveal Early Signaling Events in the Osmotic Stress Response1[W][OPEN

    PubMed Central

    E. Stecker, Kelly; Minkoff, Benjamin B.; Sussman, Michael R.

    2014-01-01

    Elucidating how plants sense and respond to water loss is important for identifying genetic and chemical interventions that may help sustain crop yields in water-limiting environments. Currently, the molecular mechanisms involved in the initial perception and response to dehydration are not well understood. Modern mass spectrometric methods for quantifying changes in the phosphoproteome provide an opportunity to identify key phosphorylation events involved in this process. Here, we have used both untargeted and targeted isotope-assisted mass spectrometric methods of phosphopeptide quantitation to characterize proteins in Arabidopsis (Arabidopsis thaliana) whose degree of phosphorylation is rapidly altered by hyperosmotic treatment. Thus, protein phosphorylation events responsive to 5 min of 0.3 m mannitol treatment were first identified using 15N metabolic labeling and untargeted mass spectrometry with a high-resolution ion-trap instrument. The results from these discovery experiments were then validated using targeted Selected Reaction Monitoring mass spectrometry with a triple quadrupole. Targeted Selected Reaction Monitoring experiments were conducted with plants treated under nine different environmental perturbations to determine whether the phosphorylation changes were specific for osmosignaling or involved cross talk with other signaling pathways. The results indicate that regulatory proteins such as members of the mitogen-activated protein kinase family are specifically phosphorylated in response to osmotic stress. Proteins involved in 5′ messenger RNA decapping and phosphatidylinositol 3,5-bisphosphate synthesis were also identified as targets of dehydration-induced phosphoregulation. The results of these experiments demonstrate the utility of targeted phosphoproteomic analysis in understanding protein regulation networks and provide new insight into cellular processes involved in the osmotic stress response. PMID:24808101

  20. STRUCTURAL ANALYSES OF FUEL CASKS SUBJECTED TO BOLT PRELOAD, INTERNAL PRESSURE AND SEQUENTIAL DYNAMIC IMPACTS

    SciTech Connect

    Wu, T

    2009-06-25

    Large fuel casks subjected to the combined loads of closure bolt tightening, internal pressure and sequential dynamic impacts present challenges when evaluating their performance in the Hypothetical Accident Conditions (HAC) specified in the Code of Federal Regulations Title 10 Part 71 (10CFR71). Testing is often limited by cost, difficulty in preparing test units and the limited availability of facilities which can carry out such tests. In the past, many casks were evaluated without testing by using simplified analytical methods. In addition, there are no realistic analyses of closure bolt stresses for HAC conditions reported in the open literature. This paper presents a numerical technique for analyzing the accumulated damages of a large fuel cask caused by the sequential loads of the closure bolt tightening and the internal pressure as well as the drop and crash dynamic loads. The bolt preload and the internal pressure are treated as quasi-static loads so that the finite element method with explicit numerical integration scheme based on the theory of wave propagation can be applied. The dynamic impacts with short durations such as the 30-foot drop and the 40-inch puncture for the hypothetical accident conditions specified in 10CFR71 are also analyzed by using the finite-element method with explicit numerical integration scheme.

  1. Regulation Dynamics of Leishmania Differentiation: Deconvoluting Signals and Identifying Phosphorylation Trends*

    PubMed Central

    Tsigankov, Polina; Gherardini, Pier Federico; Helmer-Citterich, Manuela; Späth, Gerald F.; Myler, Peter J.; Zilberstein, Dan

    2014-01-01

    Leishmania are obligatory intracellular parasitic protozoa that cause a wide range of diseases in humans, cycling between extracellular promastigotes in the mid-gut of sand flies and intracellular amastigotes in the phagolysosomes of mammalian macrophages. Although many of the molecular mechanisms of development inside macrophages remain a mystery, the development of a host-free system that simulates phagolysosome conditions (37 °C and pH 5.5) has provided new insights into these processes. The time course of promastigote-to-amastigote differentiation can be divided into four morphologically distinct phases: I, signal perception (0–5 h after exposure); II, movement cessation and aggregation (5–10 h); III, amastigote morphogenesis (10–24 h); and IV, maturation (24–120 h). Transcriptomic and proteomic analyses have indicated that differentiation is a coordinated process that results in adaptation to life inside phagolysosomes. Recent phosphoproteomic analysis revealed extensive differences in phosphorylation between promastigotes and amastigotes and identified stage-specific phosphorylation motifs. We hypothesized that the differentiation signal activates a phosphorylation pathway that initiates Leishmania transformation, and here we used isobaric tags for relative and absolute quantitation to interrogate the dynamics of changes in the phosphorylation profile during Leishmania donovani promastigote-to-amastigote differentiation. Analysis of 163 phosphopeptides (from 106 proteins) revealed six distinct kinetic profiles; with increases in phosphorylation predominated during phases I and III, whereas phases II and IV were characterized by greater dephosphorylation. Several proteins (including a protein kinase) were phosphorylated in phase I after exposure to the complete differentiation signal (i.e. signal-specific; 37 °C and pH 5.5), but not after either of the physical parameters separately. Several other protein kinases (including regulatory subunits) and

  2. Combined analytical and numerical approaches in Dynamic Stability analyses of engineering systems

    NASA Astrophysics Data System (ADS)

    Náprstek, Jiří

    2015-03-01

    Dynamic Stability is a widely studied area that has attracted many researchers from various disciplines. Although Dynamic Stability is usually associated with mechanics, theoretical physics or other natural and technical disciplines, it is also relevant to social, economic, and philosophical areas of our lives. Therefore, it is useful to occasionally highlight the general aspects of this amazing area, to present some relevant examples and to evaluate its position among the various branches of Rational Mechanics. From this perspective, the aim of this study is to present a brief review concerning the Dynamic Stability problem, its basic definitions and principles, important phenomena, research motivations and applications in engineering. The relationships with relevant systems that are prone to stability loss (encountered in other areas such as physics, other natural sciences and engineering) are also noted. The theoretical background, which is applicable to many disciplines, is presented. In this paper, the most frequently used Dynamic Stability analysis methods are presented in relation to individual dynamic systems that are widely discussed in various engineering branches. In particular, the Lyapunov function and exponent procedures, Routh-Hurwitz, Liénard, and other theorems are outlined together with demonstrations. The possibilities for analytical and numerical procedures are mentioned together with possible feedback from experimental research and testing. The strengths and shortcomings of these approaches are evaluated together with examples of their effective complementing of each other. The systems that are widely encountered in engineering are presented in the form of mathematical models. The analyses of their Dynamic Stability and post-critical behaviour are also presented. The stability limits, bifurcation points, quasi-periodic response processes and chaotic regimes are discussed. The limit cycle existence and stability are examined together with their

  3. Genetic and functional analyses demonstrate a role for abnormal glycinergic signaling in autism.

    PubMed

    Pilorge, M; Fassier, C; Le Corronc, H; Potey, A; Bai, J; De Gois, S; Delaby, E; Assouline, B; Guinchat, V; Devillard, F; Delorme, R; Nygren, G; Råstam, M; Meier, J C; Otani, S; Cheval, H; James, V M; Topf, M; Dear, T N; Gillberg, C; Leboyer, M; Giros, B; Gautron, S; Hazan, J; Harvey, R J; Legendre, P; Betancur, C

    2016-07-01

    Autism spectrum disorder (ASD) is a common neurodevelopmental condition characterized by marked genetic heterogeneity. Recent studies of rare structural and sequence variants have identified hundreds of loci involved in ASD, but our knowledge of the overall genetic architecture and the underlying pathophysiological mechanisms remains incomplete. Glycine receptors (GlyRs) are ligand-gated chloride channels that mediate inhibitory neurotransmission in the adult nervous system but exert an excitatory action in immature neurons. GlyRs containing the α2 subunit are highly expressed in the embryonic brain, where they promote cortical interneuron migration and the generation of excitatory projection neurons. We previously identified a rare microdeletion of the X-linked gene GLRA2, encoding the GlyR α2 subunit, in a boy with autism. The microdeletion removes the terminal exons of the gene (GLRA2(Δex8-9)). Here, we sequenced 400 males with ASD and identified one de novo missense mutation, p.R153Q, absent from controls. In vitro functional analysis demonstrated that the GLRA2(Δex8)(-)(9) protein failed to localize to the cell membrane, while the R153Q mutation impaired surface expression and markedly reduced sensitivity to glycine. Very recently, an additional de novo missense mutation (p.N136S) was reported in a boy with ASD, and we show that this mutation also reduced cell-surface expression and glycine sensitivity. Targeted glra2 knockdown in zebrafish induced severe axon-branching defects, rescued by injection of wild type but not GLRA2(Δex8-9) or R153Q transcripts, providing further evidence for their loss-of-function effect. Glra2 knockout mice exhibited deficits in object recognition memory and impaired long-term potentiation in the prefrontal cortex. Taken together, these results implicate GLRA2 in non-syndromic ASD, unveil a novel role for GLRA2 in synaptic plasticity and learning and memory, and link altered glycinergic signaling to social and cognitive

  4. Dynamics of BMP signaling in limb bud mesenchyme and polydactyly.

    PubMed

    Norrie, Jacqueline L; Lewandowski, Jordan P; Bouldin, Cortney M; Amarnath, Smita; Li, Qiang; Vokes, Martha S; Ehrlich, Lauren I R; Harfe, Brian D; Vokes, Steven A

    2014-09-15

    Mutations in the Bone Morphogenetic Protein (BMP) pathway are associated with a range of defects in skeletal formation. Genetic analysis of BMP signaling requirements is complicated by the presence of three partially redundant BMPs that are required for multiple stages of limb development. We generated an inducible allele of a BMP inhibitor, Gremlin, which reduces BMP signaling. We show that BMPs act in a dose and time dependent manner in which early reduction of BMPs result in digit loss, while inhibiting overall BMP signaling between E10.5 and E11.5 allows polydactylous digit formation. During this period, inhibiting BMPs extends the duration of FGF signaling. Sox9 is initially expressed in normal digit ray domains but at reduced levels that correlate with the reduction in BMP signaling. The persistence of elevated FGF signaling likely promotes cell proliferation and survival, inhibiting the activation of Sox9 and secondarily, inhibiting the differentiation of Sox9-expressing chondrocytes. Our results provide new insights into the timing and clarify the mechanisms underlying BMP signaling during digit morphogenesis. PMID:25034710

  5. Dynamics of BMP Signaling in Limb Bud Mesenchyme and Polydactyly

    PubMed Central

    Norrie, Jacqueline L.; Lewandowski, Jordan P.; Bouldin, Cortney M.; Amarnath, Smita; Li, Qiang; Vokes, Martha S.; Ehrlich, Lauren I. R.; Harfe, Brian D.; Vokes, Steven A.

    2014-01-01

    Mutations in the Bone Morphogenetic Protein (BMP) pathway are associated with a range of defects in skeletal formation. Genetic analysis of BMP signaling requirements is complicated by the presence of three partially redundant BMPs that are required for multiple stages of limb development. We generated an inducible allele of a BMP inhibitor, Gremlin, which reduces BMP signaling. We show that BMPs act in a dose and time dependent manner in which early reduction of BMPs result in digit loss, while inhibiting overall BMP signaling between E10.5 and E11.5 allows polydactylous digit formation. During this period, inhibiting BMPs extends the duration of FGF signaling. Sox9 is initially expressed in normal digit ray domains but at reduced levels that correlate with the reduction in BMP signaling. The persistence of elevated FGF signaling likely promotes cell proliferation and survival, inhibiting the activation of Sox9 and secondarily, inhibiting the differentiation of Sox9-expressing chondrocytes. Our results provide new insights into the timing and clarify the mechanisms underlying BMP signaling during digit morphogenesis. PMID:25034710

  6. Spatially uniform and nonuniform analyses of electroencephalographic dynamics,with application to the topography of the alpha rhythm

    NASA Astrophysics Data System (ADS)

    O'Connor, S. C.; Robinson, P. A.

    2004-07-01

    Corticothalamic dynamics are investigated using a model in which spatial nonuniformities are incorporated via the coupling of spatial eigenmodes. Comparison of spectra generated using the nonuniform analysis with those generated using a uniform one demonstrates that, for most frequencies, local activity is only weakly dependent on activity elsewhere in the cortex; however, dispersion of low-wave-number activity ensures that distant dynamics influence local dynamics at low frequencies (below approximately 2Hz ), and at the alpha frequency (approximately 10Hz ), where propagating signals are inherently weakly damped, and wavelengths are large. When certain model parameters have similar spatial profiles, as is expected from physiology, the low-frequency discrepancies tend to cancel, and the uniform analysis with local parameter values is an adequate approximation to the full nonuniform one across the whole spectrum, at least for large-scale nonuniformities. After comparing the uniform and nonuniform analyses, we consider one possible application of the nonuniform analysis: studying the phenomenon of occipital alpha dominance, whereby the alpha frequency and power are greater at the back of the head (occipitally) than at the front. In order to infer realistic nonuniformities in the model parameters, the uniform version of the model is first fitted to data recorded from 98 normal subjects in a waking, eyes-closed state. This yields a set of parameters at each of five electrode sites along the midline. The inferred parameter nonuniformities are consistent with anatomical and physiological constraints. Introducing these spatial profiles into the full nonuniform model then quantitatively reproduces observed site-dependent variations in the alpha power and frequency. The results confirm that the frequency shift is mainly due to a decrease in the corticothalamic propagation delay, but indicate that the delay nonuniformity cannot account for the observed occipital increase in

  7. Northern Finland Seismological Network: a tool to analyse long-period seismological signals

    NASA Astrophysics Data System (ADS)

    Kozlovskaya, Elena; Hurskainen, Riitta

    2014-05-01

    -period glacial events from Greenland in the period range of 30-140 s, but also other slow events originating from the northern part of the Mid-Atlantic Ridge, as well as and long-period seismic signals from events originating from Arctic and Russia. Slow events are rarely reported by seismological agencies, because routine methods of events detection are based on analysis of short-period body waves. This motivated further development and enhancement of the NFSN. In 2013-2014 three new VBB seismic stations will be installed in the Finnish Lapland. Together with the existing NFSN station, they will form a broadband seismic array aiming at detection and location of seismic events in long-period range. In our presentation we discuss factors affecting performance of VBB seismometers at long periods and problems connected with identification and location of slow events by array techniques.

  8. Investigating transport properties and turbidity dynamics of a karst aquifer using correlation, spectral, and wavelet analyses

    NASA Astrophysics Data System (ADS)

    Massei, N.; Dupont, J. P.; Mahler, B. J.; Laignel, B.; Fournier, M.; Valdes, D.; Ogier, S.

    2006-09-01

    SummaryIn many places throughout the world, drinking water is frequently contaminated by turbidity. Such turbidity, however, as representative of particle transport, can be used as to trace certain features of particle transport properties. In order to investigate the relation between particle and dissolved species transport and hydrodynamics in karst systems, correlation and spectral analyses were performed on time series of rainfall (input signal), and water level, specific conductance, and turbidity (output signals) at a karst spring system in the chalk aquifer of the lower Seine valley, France. This system is composed of a spring connected to a sinkhole on the chalk plateau where a small creek enters the subsurface. The autocorrelation functions for water level and turbidity showed a short memory effect, demonstrating the short duration of the influence of flood events on these two parameters, whereas specific conductance (representing less-mineralized storm-derived water) had a much longer memory effect. These results were interpreted as reflecting the rapid reactivity of the spring to rain events, with storage of water in the fissured chalk explaining the longer memory effect for specific conductance than for particles. Energy spectra computed by fast Fourier transform of autocorrelation functions showed a strong structure in the output signals, whereas the input signal (rainfall) was random, thus allowing assessment and comparison of system behaviour regarding dissolved and solid transport, as well as hydraulics. Cross-correlation functions (which allow an assessment of impulse response functions) confirmed the low inertia of the system for water level and turbidity and the much higher inertia for specific conductance. In addition to the main peak, two secondary peaks in the cross-correlation functions suggest the existence of additional flowpaths that might involve the contribution of other point-source recharge and/or delayed infiltration through the

  9. Dynamic speckle-interferometer for intracellular processes analyses at high optical magnification

    NASA Astrophysics Data System (ADS)

    Baharev, A. A.; Vladimirov, A. P.; Malygin, A. S.; Mikhailova, Y. A.; Novoselova, I. A.; Yakin, D. I.; Druzhinin, A. V.

    2015-05-01

    At present work dynamic of biospeckles is used for studying processes occurring in cells which arranged in the one layer. The basis of many diseases is changes in the structural and functional properties of the molecular cells components as caused by the influence of external factors and internal functional disorders. Purpose of work is approbation of speckle-interferometer designed for the analysis of cellular metabolism in individual cells. As a parameter, characterizing the metabolic activity of cells used the value of the correlation coefficient (η) of optical signals proportional to the radiation intensity I, recorded at two points in time t. At 320x magnification for the cell diameter of 20 microns value η can be determined in the area size of 6 microns.

  10. Structural Dynamic Analyses And Test Predictions For Spacecraft Structures With Non-Linearities

    NASA Astrophysics Data System (ADS)

    Vergniaud, Jean-Baptiste; Soula, Laurent; Newerla, Alfred

    2012-07-01

    The overall objective of the mechanical development and verification process is to ensure that the spacecraft structure is able to sustain the mechanical environments encountered during launch. In general the spacecraft structures are a-priori assumed to behave linear, i.e. the responses to a static load or dynamic excitation, respectively, will increase or decrease proportionally to the amplitude of the load or excitation induced. However, past experiences have shown that various non-linearities might exist in spacecraft structures and the consequences of their dynamic effects can significantly affect the development and verification process. Current processes are mainly adapted to linear spacecraft structure behaviour. No clear rules exist for dealing with major structure non-linearities. They are handled outside the process by individual analysis and margin policy, and analyses after tests to justify the CLA coverage. Non-linearities can primarily affect the current spacecraft development and verification process on two aspects. Prediction of flights loads by launcher/satellite coupled loads analyses (CLA): only linear satellite models are delivered for performing CLA and no well-established rules exist how to properly linearize a model when non- linearities are present. The potential impact of the linearization on the results of the CLA has not yet been properly analyzed. There are thus difficulties to assess that CLA results will cover actual flight levels. Management of satellite verification tests: the CLA results generated with a linear satellite FEM are assumed flight representative. If the internal non- linearities are present in the tested satellite then there might be difficulties to determine which input level must be passed to cover satellite internal loads. The non-linear behaviour can also disturb the shaker control, putting the satellite at risk by potentially imposing too high levels. This paper presents the results of a test campaign performed in

  11. Intracellular Information Processing through Encoding and Decoding of Dynamic Signaling Features

    PubMed Central

    Makadia, Hirenkumar K.; Schwaber, James S.; Vadigepalli, Rajanikanth

    2015-01-01

    Cell signaling dynamics and transcriptional regulatory activities are variable within specific cell types responding to an identical stimulus. In addition to studying the network interactions, there is much interest in utilizing single cell scale data to elucidate the non-random aspects of the variability involved in cellular decision making. Previous studies have considered the information transfer between the signaling and transcriptional domains based on an instantaneous relationship between the molecular activities. These studies predict a limited binary on/off encoding mechanism which underestimates the complexity of biological information processing, and hence the utility of single cell resolution data. Here we pursue a novel strategy that reformulates the information transfer problem as involving dynamic features of signaling rather than molecular abundances. We pursue a computational approach to test if and how the transcriptional regulatory activity patterns can be informative of the temporal history of signaling. Our analysis reveals (1) the dynamic features of signaling that significantly alter transcriptional regulatory patterns (encoding), and (2) the temporal history of signaling that can be inferred from single cell scale snapshots of transcriptional activity (decoding). Immediate early gene expression patterns were informative of signaling peak retention kinetics, whereas transcription factor activity patterns were informative of activation and deactivation kinetics of signaling. Moreover, the information processing aspects varied across the network, with each component encoding a selective subset of the dynamic signaling features. We developed novel sensitivity and information transfer maps to unravel the dynamic multiplexing of signaling features at each of these network components. Unsupervised clustering of the maps revealed two groups that aligned with network motifs distinguished by transcriptional feedforward vs feedback interactions. Our new

  12. Stream restoration in dynamic fluvial systems: Scientific approaches, analyses, and tools

    NASA Astrophysics Data System (ADS)

    Schultz, Colin

    2012-04-01

    In the United States the average annual investment in river restoration programs is approximately $1 billion. Despite this burgeoning industry, the National Water Quality Inventory, which tracks the health of the nation's rivers, has shown no serious improvement in cumulative river health since the early 1990s. In the AGU monographStream Restoration in Dynamic Fluvial Systems: Scientific Approaches, Analyses, and Tools, editors Andrew Simon, Sean J. Bennett, and Janine M. Castro pull together the latest evidence-based understanding of stream restoration practices, with an aim of guiding the further development of the field and helping to right its apparently unsuccessful course. In this interview, Eos talks to Sean J. Bennett, University of Buffalo, about the culture, practice, and promise of restoring rivers.

  13. A comprehensive tool to analyse dynamic log files from an Elekta-Synergy accelerator

    NASA Astrophysics Data System (ADS)

    Arumugam, Sankar; Xing, Aitang; Pagulayan, Claire; Holloway, Lois

    2014-03-01

    This study presents the development of a software tool 'Treat Check' to analyse the dynamic log files from an Elekta - Synergy accelerator. The software generates formatted output in the form of a plot presenting errors in various treatment delivery parameters such as gantry angle, Multi Leaf Collimator (MLC) leaf position, jaw position and Monitor Units (MU) for each of the control-points (CP) of the treatment beam. The plots are automatically saved in Portable Document Format (pdf). The software also has the functionality to introduce these treatment delivery errors into the original plan in the Pinnacle (Philips) treatment planning system (TPS) in order to assess the clinical impact of treatment delivery errors on delivered dose.

  14. Three isoparametric solid elements for NASTRAN. [for static, dynamic, buckling, and heat transfer analyses

    NASA Technical Reports Server (NTRS)

    Johnson, S. E.; Field, E. I.

    1973-01-01

    Linear, quadratic, and cubic isoparametric hexahedral solid elements have been added to the element library of NASTRAN. These elements are available for static, dynamic, buckling, and heat-transfer analyses. Because the isoparametric element matrices are generated by direct numerical integration over the volume of the element, variations in material properties, temperatures, and stresses within the elements are represented in the computations. In order to compare the accuracy of the new elements, three similar models of a slender cantilever were developed, one for each element. All elements performed well. As expected, however, the linear element model yielded excellent results only when shear behavior predominated. In contrast, the results obtained from the quadratic and cubic element models were excellent in both shear and bending.

  15. Modeling Oncogenic Signaling in Colon Tumors by Multidirectional Analyses of Microarray Data Directed for Maximization of Analytical Reliability

    PubMed Central

    Rubel, Tymon; Paziewska, Agnieszka; Mikula, Michal; Jarosz, Dorota; Pachlewski, Jacek; Oledzki, Janusz; Ostrowsk, Jerzy

    2010-01-01

    Background Clinical progression of colorectal cancers (CRC) may occur in parallel with distinctive signaling alterations. We designed multidirectional analyses integrating microarray-based data with biostatistics and bioinformatics to elucidate the signaling and metabolic alterations underlying CRC development in the adenoma-carcinoma sequence. Methodology/Principal Findings Studies were performed on normal mucosa, adenoma, and carcinoma samples obtained during surgery or colonoscopy. Collections of cryostat sections prepared from the tissue samples were evaluated by a pathologist to control the relative cell type content. The measurements were done using Affymetrix GeneChip HG-U133plus2, and probe set data was generated using two normalization algorithms: MAS5.0 and GCRMA with least-variant set (LVS). The data was evaluated using pair-wise comparisons and data decomposition into singular value decomposition (SVD) modes. The method selected for the functional analysis used the Kolmogorov-Smirnov test. Expressional profiles obtained in 105 samples of whole tissue sections were used to establish oncogenic signaling alterations in progression of CRC, while those representing 40 microdissected specimens were used to select differences in KEGG pathways between epithelium and mucosa. Based on a consensus of the results obtained by two normalization algorithms, and two probe set sorting criteria, we identified 14 and 17 KEGG signaling and metabolic pathways that are significantly altered between normal and tumor samples and between benign and malignant tumors, respectively. Several of them were also selected from the raw microarray data of 2 recently published studies (GSE4183 and GSE8671). Conclusion/Significance Although the proposed strategy is computationally complex and labor–intensive, it may reduce the number of false results. PMID:20957034

  16. Analyses of the dynamic docking test system for advanced mission docking system test programs. [Apollo Soyuz Test Project

    NASA Technical Reports Server (NTRS)

    Gates, R. M.; Williams, J. E.

    1974-01-01

    Results are given of analytical studies performed in support of the design, implementation, checkout and use of NASA's dynamic docking test system (DDTS). Included are analyses of simulator components, a list of detailed operational test procedures, a summary of simulator performance, and an analysis and comparison of docking dynamics and loads obtained by test and analysis.

  17. Analysing land cover changes for understanding of forest dynamics using temporal forest management plans.

    PubMed

    Kadioğullari, Ali İhsan; Sayin, Mehmet Ali; Çelįk, Durmuş Ali; Borucu, Süleyman; Çįl, Bayram; Bulut, Sinan

    2014-04-01

    This study analyses forest dynamics and land use/land cover change over a 43-year period using spatial-stand-type maps of temporal forest management plans of Karaisalı Forest Enterprise in the Eastern Mediterranean Region of Turkey. Stand parameters (tree species, crown closures and developmental stages) of the dynamics and changes caused by natural or artificial intervention were introduced and mapped in a Geographic Information System (GIS) and subjected to fragmentation analysis using FRAGSTATS. The Karaisalı Forest Enterprise was first planned in 1969 and then the study area was planned under the Mediterranean Forest Use project in 1991 and five-term forest management plans were made. In this study, we analysed only four periods (excluding 1982 revision plans): 1969, 1991, 2002 and 2012. Between 1969 and 2012, overall changes included a net increase of 3,026 ha in forested areas. Cumulative forest improvement accounted for 2.12% and the annual rate of total forest improvement averaged 0.08%. In addition, productive forest areas increased from 36,174 to 70,205 ha between 1969 and 2012. This translates into an average annual productive forest improvement rate of 1.54%. At the same time, fully covered forest areas with crown closure of "3" (>70%) increased about 21,321 ha, and young forest areas in developmental stage of "a" (diameter at breast height (dbh) < 8 cm) increased from 716 to 13,305 ha over the 43-year study period. Overall changes show that productive and fully covered forest areas have increased egregiously with a focus on regenerated and young developmental stages. A spatial analysis of metrics over the 43-year study period indicated a more fragmented landscape resulting in a susceptible forest to harsh disturbances. PMID:24254492

  18. Diverse sensitivity thresholds in dynamic signaling responses by social amoebae.

    PubMed

    Wang, C Joanne; Bergmann, Adriel; Lin, Benjamin; Kim, Kyuri; Levchenko, Andre

    2012-02-28

    The complex transition from a single-cell to a multicellular life form during the formation of a fruiting body by the amoeba Dictyostelium discoideum is accompanied by a pulsatile collective signaling process that instigates chemotaxis of the constituent cells. Although the cells used for the analysis of this phenomenon are normally genetically identical (isogenic), it is not clear whether they are equally responsive to the waves of the signaling stimulus, nor is it clear how responses across the population influence collective cell behavior. Here, we found that isogenic Dictyostelium cells displayed differing sensitivities to the chemoattractant cyclic adenosine monophosphate (cAMP). Furthermore, the resulting signaling responses could be explained by a model in which cells are refractory to further stimulation for 5 to 6 min after the initial input and the signaling output is amplified, with the amplification threshold varying across the cells in the population. This pathway structure could explain intracellular amplification of the chemoattractant gradient during cell migration. The new model predicts that diverse cell responsiveness can facilitate collective cell behavior, specifically due to the presence of a small number of cells in the population with increased responsiveness that aid in propagating the initial cAMP signaling wave across the cell population. PMID:22375055

  19. Automated Analysis of Dynamic Ca2+ Signals in Image Sequences

    PubMed Central

    Francis, Michael; Waldrup, Josh; Qian, Xun; Taylor, Mark S.

    2014-01-01

    Intracellular Ca2+ signals are commonly studied with fluorescent Ca2+ indicator dyes and microscopy techniques. However, quantitative analysis of Ca2+ imaging data is time consuming and subject to bias. Automated signal analysis algorithms based on region of interest (ROI) detection have been implemented for one-dimensional line scan measurements, but there is no current algorithm which integrates optimized identification and analysis of ROIs in two-dimensional image sequences. Here an algorithm for rapid acquisition and analysis of ROIs in image sequences is described. It utilizes ellipses fit to noise filtered signals in order to determine optimal ROI placement, and computes Ca2+ signal parameters of amplitude, duration and spatial spread. This algorithm was implemented as a freely available plugin for ImageJ (NIH) software. Together with analysis scripts written for the open source statistical processing software R, this approach provides a high-capacity pipeline for performing quick statistical analysis of experimental output. The authors suggest that use of this analysis protocol will lead to a more complete and unbiased characterization of physiologic Ca2+ signaling. PMID:24962784

  20. Dopamine D1 signaling organizes network dynamics underlying working memory

    PubMed Central

    Roffman, Joshua L.; Tanner, Alexandra S.; Eryilmaz, Hamdi; Rodriguez-Thompson, Anais; Silverstein, Noah J.; Ho, New Fei; Nitenson, Adam Z.; Chonde, Daniel B.; Greve, Douglas N.; Abi-Dargham, Anissa; Buckner, Randy L.; Manoach, Dara S.; Rosen, Bruce R.; Hooker, Jacob M.; Catana, Ciprian

    2016-01-01

    Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled by simultaneous positron emission tomography–magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory. Among network territories, mean cortical D1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, mean cortical D1 density predicted working memory–emergent decoupling of the frontoparietal and default networks, which respectively manage task-related and internal stimuli. In contrast, striatal D1 predicted opposing effects within these two networks but no between-network effects. These findings specifically link cortical dopamine signaling to network crosstalk that redirects cognitive resources to working memory, echoing neuromodulatory effects of D1 signaling on the level of cortical microcircuits. PMID:27386561

  1. Oscillatory Dynamics of the Extracellular Signal-regulated Kinase Pathway

    SciTech Connect

    Shankaran, Harish; Wiley, H. S.

    2010-12-01

    The extracellular signal-regulated kinase (ERK) pathway is a central signaling pathway in development and disease and is regulated by multiple negative and positive feedback loops. Recent studies have shown negative feedback from ERK to upstream regulators can give rise to biochemical oscillations with a periodicity of between 15-30 minutes. Feedback due to the stimulated transcription of negative regulators of the ERK pathway can also give rise to transcriptional oscillations with a periodicity of 1-2h. The biological significance of these oscillations is not clear, but recent evidence suggests that transcriptional oscillations participate in developmental processes, such as somite formation. Biochemical oscillations are more enigmatic, but could provide a mechanism for encoding different types of inputs into a common signaling pathway.

  2. Dynamical Low-energy Electron Diffraction Analyses of Clean and H-adsorbed Ir(111) Surfaces

    NASA Astrophysics Data System (ADS)

    Matsumoto, Masuaki; Ogura, Syohei; Fukutani, Katsuyuki; Okano, Tatsuo; Okada, Michio

    Structures of Clean and H-adsorbed Ir(111) surfaces were studied by dynamical analyses of low-energy electron diffraction (LEED). LEED pattern for the Clean Ir(111) surface was 1×1. Dynamical analysis of LEED spot intensity vs incident electron enegy (I-V) curves for the clean Ir(111) surface revealed that the layer distance between the 1st and the 2nd layers (d12) equals to 0.2207±0.002 nm, which is almost equal to the bulk value (0.2217 nm). It appears that our result contradicts an previous report, which concluded that d12 equals to 0.216 nm which is 2.6% smaller than the bulk value. However their error bar was so large (±0.01 nm) that it is suggested that our result is the accurate atomic structure of the clean Ir(111) surface. LEED pattern was almost unchanged by H adsorption of 1 ML (1.56×1015 cm-2) at 80 K. The difference between LEED I-V curves before and after hydrogen adsorption was very small and it was impossible to determine the adsorption structure on Ir(111) but it can be conculded that no reconstruction occurs and only a very small relaxation occurs by the adsorption of hydrogen on Ir(111) surface.

  3. Detailed analyses of dynamic and static errors in neutron radiography testing

    SciTech Connect

    Joo, H.; Glickstein, S.S.

    1999-01-01

    Neutron radiography systems are being used for real-time visualization of the dynamic behavior as well as time-averaged measurements of spatial vapor fraction distributions for two phase fluids. The extraction of quantitative data on vapor-liquid flow fields is a significant advance in the methodology of fundamental two-phase flow experimentation. The data in the form of video images are typically recorded on videotape at 30 frames per second. Image analysis of the video pictures is used to extract time-dependent or time-averaged data. The determination of the average vapor fraction requires averaging of the logarithm of time-dependent intensity measurements of the neutron beam (gray scale distribution of the image) that passes through the fluid. This could be significantly different than averaging the intensity of the transmitted beam and then taking the logarithm of that term. This is termed the dynamic error (error in the time-averaged vapor fractions due t the inherent time-dependence of the measured data) and is separate from the static error (statistical sampling uncertainty). The results provide insight into the characteristics of these errors and help to quantify achievable bounds on the limits of these errors. The static error was determined by the uncertainties of measured beam intensities. It was found that the maximum static error increases as liquid thickness increases and can be reduced by increasing the neutron source strength. The dynamic error increased with large fluctuations in the local vapor fractions and with increasing liquid thickness. Detailed analyses of both sources of errors are discussed.

  4. Lipid body accumulation alters calcium signaling dynamics in immune cells.

    PubMed

    Greineisen, William E; Speck, Mark; Shimoda, Lori M N; Sung, Carl; Phan, Nolwenn; Maaetoft-Udsen, Kristina; Stokes, Alexander J; Turner, Helen

    2014-09-01

    There is well-established variability in the numbers of lipid bodies (LB) in macrophages, eosinophils, and neutrophils. Similarly to the steatosis observed in adipocytes and hepatocytes during hyperinsulinemia and nutrient overload, immune cell LB hyper-accumulate in response to bacterial and parasitic infection and inflammatory presentations. Recently we described that hyperinsulinemia, both in vitro and in vivo, drives steatosis and phenotypic changes in primary and transformed mast cells and basophils. LB reach high numbers in these steatotic cytosols, and here we propose that they could dramatically impact the transcytoplasmic signaling pathways. We compared calcium release and influx responses at the population and single cell level in normal and steatotic model mast cells. At the population level, all aspects of FcɛRI-dependent calcium mobilization, as well as activation of calcium-dependent downstream signaling targets such as NFATC1 phosphorylation are suppressed. At the single cell level, we demonstrate that LB are both sources and sinks of calcium following FcɛRI cross-linking. Unbiased analysis of the impact of the presence of LB on the rate of trans-cytoplasmic calcium signals suggest that LB enrichment accelerates calcium propagation, which may reflect a Bernoulli effect. LB abundance thus impacts this fundamental signaling pathway and its downstream targets. PMID:25016314

  5. Early signaling dynamics of the epidermal growth factor receptor.

    PubMed

    Reddy, Raven J; Gajadhar, Aaron S; Swenson, Eric J; Rothenberg, Daniel A; Curran, Timothy G; White, Forest M

    2016-03-15

    Despite extensive study of the EGF receptor (EGFR) signaling network, the immediate posttranslational changes that occur in response to growth factor stimulation remain poorly characterized; as a result, the biological mechanisms underlying signaling initiation remain obscured. To address this deficiency, we have used a mass spectrometry-based approach to measure system-wide phosphorylation changes throughout the network with 10-s resolution in the 80 s after stimulation in response to a range of eight growth factor concentrations. Significant changes were observed on proteins far downstream in the network as early as 10 s after stimulation, indicating a system capable of transmitting information quickly. Meanwhile, canonical members of the EGFR signaling network fall into clusters with distinct activation patterns. Src homology 2 domain containing transforming protein (Shc) and phosphoinositol 3-kinase (PI3K) phosphorylation levels increase rapidly, but equilibrate within 20 s, whereas proteins such as Grb2-associated binder-1 (Gab1) and SH2-containing tyrosine phosphatase (SHP2) show slower, sustained increases. Proximity ligation assays reveal that Shc and Gab1 phosphorylation patterns are representative of separate timescales for physical association with the receptor. Inhibition of phosphatases with vanadate reveals site-specific regulatory mechanisms and also uncovers primed activating components in the network, including Src family kinases, whose inhibition affects only a subset of proteins within the network. The results presented highlight the complexity of signaling initiation and provide a window into exploring mechanistic hypotheses about receptor tyrosine kinase (RTK) biology. PMID:26929352

  6. Lipid body accumulation alters calcium signaling dynamics in immune cells

    PubMed Central

    Greineisen, William E.; Speck, Mark; Shimoda, Lori M.N.; Sung, Carl; Phan, Nolwenn; Maaetoft-Udsen, Kristina; Stokes, Alexander J.; Turner, Helen

    2014-01-01

    Summary There is well-established variability in the numbers of lipid bodies (LB) in macrophages, eosinophils, and neutrophils. Similarly to the steatosis observed in adipocytes and hepatocytes during hyperinsulinemia and nutrient overload, immune cell LB hyper-accumulate in response to bacterial and parasitic infection and inflammatory presentations. Recently we described that hyperinsulinemia, both in vitro and in vivo, drives steatosis and phenotypic changes in primary and transformed mast cells and basophils. LB reach high numbers in these steatotic cytosols, and here we propose that they could dramatically impact the transcytoplasmic signaling pathways. We compared calcium release and influx responses at the population and single cell level in normal and steatotic model mast cells. At the population level, all aspects of FcεRI-dependent calcium mobilization, as well as activation of calcium-dependent downstream signalling targets such as NFATC1 phosphorylation are suppressed. At the single cell level, we demonstrate that LB are both sources and sinks of calcium following FcεRI cross-linking. Unbiased analysis of the impact of the presence of LB on the rate of trans-cytoplasmic calcium signals suggest that LB enrichment accelerates calcium propagation, which may reflect a Bernoulli effect. LB abundance thus impacts this fundamental signalling pathway and its downstream targets. PMID:25016314

  7. Group dynamics and record signals in the ant Temnothorax albipennis

    PubMed Central

    Richardson, T. O.; Christensen, K.; Franks, N. R.; Jensen, H. J.; Sendova-Franks, A. B.

    2011-01-01

    Many purely physical complex systems, in which there are both stochasticity and local interactions between the components, exhibit record dynamics. The temporal statistics of record dynamics is a Poisson process operating on a logarithmic rather than a linear time scale (i.e. a log-Poisson process). Record dynamics often drive substantial changes in complex systems when new high water marks in partially stochastic processes trigger new events. Social insect colonies are exemplary complex biological systems in which many of the local interactions of the components have been moulded by natural selection for the common good. Here, we combine experimental manipulation of ant colony demography with modelling to test the hypothesis that social interactions are the mechanism underlying the record dynamics. We found that compared with the control, log-Poisson statistics were disrupted in colonies in which the pattern of interactions was modified by the removal of the brood, and disappeared completely in ‘callow’ colonies composed entirely of very young workers from the same age cohort. We conclude that a subtle interplay between the demography of the society and the pattern of the interactions between the ants is crucial for the emergence of record dynamics. This could help identify what makes an ant colony a cohesive society. PMID:20685694

  8. Enzyme Sequestration as a Tuning Point in Controlling Response Dynamics of Signalling Networks

    PubMed Central

    Ollivier, Julien F.; Soyer, Orkun S.

    2016-01-01

    Signalling networks result from combinatorial interactions among many enzymes and scaffolding proteins. These complex systems generate response dynamics that are often essential for correct decision-making in cells. Uncovering biochemical design principles that underpin such response dynamics is a prerequisite to understand evolved signalling networks and to design synthetic ones. Here, we use in silico evolution to explore the possible biochemical design space for signalling networks displaying ultrasensitive and adaptive response dynamics. By running evolutionary simulations mimicking different biochemical scenarios, we find that enzyme sequestration emerges as a key mechanism for enabling such dynamics. Inspired by these findings, and to test the role of sequestration, we design a generic, minimalist model of a signalling cycle, featuring two enzymes and a single scaffolding protein. We show that this simple system is capable of displaying both ultrasensitive and adaptive response dynamics. Furthermore, we find that tuning the concentration or kinetics of the sequestering protein can shift system dynamics between these two response types. These empirical results suggest that enzyme sequestration through scaffolding proteins is exploited by evolution to generate diverse response dynamics in signalling networks and could provide an engineering point in synthetic biology applications. PMID:27163612

  9. Signal quality of the LHC AC dipoles and its impact on beam dynamics

    SciTech Connect

    Miyamoto, R.; Cattin, M.; Serrano, J.; Tomas, R.

    2010-05-23

    The adiabaticity of the AC dipole might be compromised by noise or unwanted frequency components in its signal. An effort has been put to characterize and optimize the signal quality of the LHC AC dipoles. The measured signal is used in realistic simulations in order to evaluate its impact on beam dynamics and to ultimately establish safe margins for the operation of the LHC AC dipoles.

  10. Distinct Signal Transduction Pathways Downstream of the (P)RR Revealed by Microarray and ChIP-chip Analyses

    PubMed Central

    Zaade, Daniela; Schmitz, Jennifer; Benke, Eileen; Klare, Sabrina; Seidel, Kerstin; Kirsch, Sebastian; Goldin-Lang, Petra; Zollmann, Frank S.; Unger, Thomas; Funke-Kaiser, Heiko

    2013-01-01

    The (pro)renin receptor ((P)RR) signaling is involved in different pathophysiologies ranging from cardiorenal end-organ damage via diabetic retinopathy to tumorigenesis. We have previously shown that the transcription factor promyelocytic leukemia zinc finger (PLZF) is an adaptor protein of the (P)RR. Furthermore, recent publications suggest that major functions of the (P)RR are mediated ligand-independently by its transmembrane and intracellular part, which acts as an accessory protein of V-ATPases. The transcriptome and recruitmentome downstream of the V-ATPase function and PLZF in the context of the (P)RR are currently unknown. Therefore, we performed a set of microarray and chromatin-immunoprecipitation (ChIP)-chip experiments using siRNA against the (P)RR, stable overexpression of PLZF, the PLZF translocation inhibitor genistein and the specific V-ATPase inhibitor bafilomycin to dissect transcriptional pathways downstream of the (P)RR. We were able to identify distinct and overlapping genetic signatures as well as novel real-time PCR-validated target genes of the different molecular functions of the (P)RR. Moreover, bioinformatic analyses of our data confirm the role of (P)RŔs signal transduction pathways in cardiovascular disease and tumorigenesis. PMID:23469216

  11. Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway

    PubMed Central

    Čokić, Vladan P.; Mossuz, Pascal; Han, Jing; Socoro, Nuria; Beleslin-Čokić, Bojana B.; Mitrović, Olivera; Subotički, Tijana; Diklić, Miloš; Leković, Danijela; Gotić, Mirjana; Puri, Raj K.; Noguchi, Constance Tom; Schechter, Alan N.

    2015-01-01

    The gene and protein expression profiles in myeloproliferative neoplasms (MPNs) may reveal gene and protein markers of a potential clinical relevance in diagnosis, treatment and prediction of response to therapy. Using cDNA microarray analysis of 25,100 unique genes, we studied the gene expression profile of CD34+ cells and granulocytes obtained from peripheral blood of subjects with essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). The microarray analyses of the CD34+ cells and granulocytes were performed from 20 de novo MPN subjects: JAK2 positive ET, PV, PMF subjects, and JAK2 negative ET/PMF subjects. The granulocytes for proteomic studies were pooled in 4 groups: PV with JAK2 mutant allele burden above 80%, ET with JAK2 mutation, PMF with JAK2 mutation and ET/PMF with no JAK2 mutation. The number of differentially regulated genes was about two fold larger in CD34+ cells compared to granulocytes. Thirty-six genes (including RUNX1, TNFRSF19) were persistently highly expressed, while 42 genes (including FOXD4, PDE4A) were underexpressed both in CD34+ cells and granulocytes. Using proteomic studies, significant up-regulation was observed for MAPK and PI3K/AKT signaling regulators that control myeloid cell apoptosis and proliferation: RAC2, MNDA, S100A8/9, CORO1A, and GNAI2. When the status of the mTOR signaling pathway related genes was analyzed, PI3K/AKT regulators were preferentially up-regulated in CD34+ cells of MPNs, with down-regulated major components of the protein complex EIF4F. Molecular profiling of CD34+ cells and granulocytes of MPN determined gene expression patterns beyond their recognized function in disease pathogenesis that included dominant up-regulation of PI3K/AKT signaling. PMID:26275051

  12. High dynamic extinction ratio and pulse modulation of optical signals

    NASA Astrophysics Data System (ADS)

    Petrov, A.; Tronev, A. V.; Lebedev, V.; Il'ichev, I. V.; Velichko, E.; Shamray, A.

    2015-11-01

    The use of a saturable absorber for increasing the extinction ratio at external modulation of optical signals is considered. An erbium doped fiber was used as the saturable absorber in the experiments. A considerable increase in the static extinction ratio (up to 50 dB) was demonstrated. A rather long erbium doped fiber relaxation time (about 10 ms) was a limiting factor in the case of pulse modulation. Ways of overcoming this drawback are discussed.

  13. Dynamics of long-distance signaling via plant vascular tissues.

    PubMed

    Notaguchi, Michitaka; Okamoto, Satoru

    2015-01-01

    Plant vascular systems are constructed by specific cell wall modifications through which cells are highly specialized to make conduits for water and nutrients. Xylem vessels are formed by thickened cell walls that remain after programmed cell death, and serve as water conduits from the root to the shoot. In contrast, phloem tissues consist of a complex of living cells, including sieve tube elements and their neighboring companion cells, and translocate photosynthetic assimilates from mature leaves to developing young tissues. Intensive studies on the content of vascular flow fluids have unveiled that plant vascular tissues transport various types of gene product, and the transport of some provides the molecular basis for the long-distance communications. Analysis of xylem sap has demonstrated the presence of proteins in the xylem transpiration stream. Recent studies have revealed that CLE and CEP peptides secreted in the roots are transported to above ground via the xylem in response to plant-microbe interaction and soil nitrogen starvation, respectively. Their leucine-rich repeat transmembrane receptors localized in the shoot phloem are required for relaying the signal from the shoot to the root. These findings well-fit to the current scenario of root-to-shoot-to-root feedback signaling, where peptide transport achieves the root-to-shoot signaling, the first half of the signaling process. Meanwhile, it is now well-evidenced that proteins and a range of RNAs are transported via the phloem translocation system, and some of those can exert their physiological functions at their destinations, including roots. Thus, plant vascular systems may serve not only as conduits for the translocation of essential substances but also as long-distance communication pathways that allow plants to adapt to changes in internal and external environments at the whole plant level. PMID:25852714

  14. Comparative genomic analyses reveal a vast, novel network of nucleotide-centric systems in biological conflicts, immunity and signaling

    PubMed Central

    Burroughs, A. Maxwell; Zhang, Dapeng; Schäffer, Daniel E.; Iyer, Lakshminarayan M.; Aravind, L.

    2015-01-01

    Cyclic di- and linear oligo-nucleotide signals activate defenses against invasive nucleic acids in animal immunity; however, their evolutionary antecedents are poorly understood. Using comparative genomics, sequence and structure analysis, we uncovered a vast network of systems defined by conserved prokaryotic gene-neighborhoods, which encode enzymes generating such nucleotides or alternatively processing them to yield potential signaling molecules. The nucleotide-generating enzymes include several clades of the DNA-polymerase β-like superfamily (including Vibrio cholerae DncV), a minimal version of the CRISPR polymerase and DisA-like cyclic-di-AMP synthetases. Nucleotide-binding/processing domains include TIR domains and members of a superfamily prototyped by Smf/DprA proteins and base (cytokinin)-releasing LOG enzymes. They are combined in conserved gene-neighborhoods with genes for a plethora of protein superfamilies, which we predict to function as nucleotide-sensors and effectors targeting nucleic acids, proteins or membranes (pore-forming agents). These systems are sometimes combined with other biological conflict-systems such as restriction-modification and CRISPR/Cas. Interestingly, several are coupled in mutually exclusive neighborhoods with either a prokaryotic ubiquitin-system or a HORMA domain-PCH2-like AAA+ ATPase dyad. The latter are potential precursors of equivalent proteins in eukaryotic chromosome dynamics. Further, components from these nucleotide-centric systems have been utilized in several other systems including a novel diversity-generating system with a reverse transcriptase. We also found the Smf/DprA/LOG domain from these systems to be recruited as a predicted nucleotide-binding domain in eukaryotic TRPM channels. These findings point to evolutionary and mechanistic links, which bring together CRISPR/Cas, animal interferon-induced immunity, and several other systems that combine nucleic-acid-sensing and nucleotide-dependent signaling

  15. Dynamics of Phosphoinositide-Dependent Signaling in Sympathetic Neurons

    PubMed Central

    Kruse, Martin; Vivas, Oscar; Traynor-Kaplan, Alexis

    2016-01-01

    In neurons, loss of plasma membrane phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] leads to a decrease in exocytosis and changes in electrical excitability. Restoration of PI(4,5)P2 levels after phospholipase C activation is therefore essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We measured dynamic changes of PI(4,5)P2, phosphatidylinositol 4-phosphate, diacylglycerol, inositol 1,4,5-trisphosphate, and Ca2+ upon muscarinic stimulation in sympathetic neurons from adult male Sprague-Dawley rats with electrophysiological and optical approaches. We used this kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show and explain faster synthesis of PI(4,5)P2 in sympathetic neurons than in electrically nonexcitable tsA201 cells. They can be used to understand dynamic effects of receptor-mediated phospholipase C activation on excitability and other PI(4,5)P2-dependent processes in neurons. SIGNIFICANCE STATEMENT Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a minor phospholipid in the cytoplasmic leaflet of the plasma membrane. Depletion of PI(4,5)P2 via phospholipase C-mediated hydrolysis leads to a decrease in exocytosis and alters electrical excitability in neurons. Restoration of PI(4,5)P2 is essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We studied the dynamics of phosphoinositide metabolism in sympathetic neurons upon muscarinic stimulation and used the kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show a several-fold faster synthesis of PI(4,5)P2 in sympathetic neurons than in an electrically nonexcitable cell line, and provide a framework for future studies of PI(4,5)P2-dependent processes in neurons. PMID:26818524

  16. Multi-Platform Metabolomic Analyses of Ergosterol-Induced Dynamic Changes in Nicotiana tabacum Cells

    PubMed Central

    Tugizimana, Fidele; Steenkamp, Paul A.; Piater, Lizelle A.; Dubery, Ian A.

    2014-01-01

    Metabolomics is providing new dimensions into understanding the intracellular adaptive responses in plants to external stimuli. In this study, a multi-technology-metabolomic approach was used to investigate the effect of the fungal sterol, ergosterol, on the metabolome of cultured tobacco cells. Cell suspensions were treated with different concentrations (0–1000 nM) of ergosterol and incubated for different time periods (0–24 h). Intracellular metabolites were extracted with two methods: a selective dispersive liquid-liquid micro-extraction and a general methanol extraction. Chromatographic techniques (GC-FID, GC-MS, GC×GC-TOF-MS, UHPLC-MS) and 1H NMR spectroscopy were used for quantitative and qualitative analyses. Multivariate data analyses (PCA and OPLS-DA models) were used to extract interpretable information from the multidimensional data generated from the analytical techniques. The results showed that ergosterol triggered differential changes in the metabolome of the cells, leading to variation in the biosynthesis of secondary metabolites. PCA scores plots revealed dose- and time-dependent metabolic variations, with optimal treatment conditions being found to be 300 nM ergosterol and an 18 h incubation period. The observed ergosterol-induced metabolic changes were correlated with changes in defence-related metabolites. The ‘defensome’ involved increases in terpenoid metabolites with five antimicrobial compounds (the bicyclic sesquiterpenoid phytoalexins: phytuberin, solavetivone, capsidiol, lubimin and rishitin) and other metabolites (abscisic acid and phytosterols) putatively identified. In addition, various phenylpropanoid precursors, cinnamic acid derivatives and - conjugates, coumarins and lignin monomers were annotated. These annotated metabolites revealed a dynamic reprogramming of metabolic networks that are functionally correlated, with a high complexity in their regulation. PMID:24498209

  17. Multi-platform metabolomic analyses of ergosterol-induced dynamic changes in Nicotiana tabacum cells.

    PubMed

    Tugizimana, Fidele; Steenkamp, Paul A; Piater, Lizelle A; Dubery, Ian A

    2014-01-01

    Metabolomics is providing new dimensions into understanding the intracellular adaptive responses in plants to external stimuli. In this study, a multi-technology-metabolomic approach was used to investigate the effect of the fungal sterol, ergosterol, on the metabolome of cultured tobacco cells. Cell suspensions were treated with different concentrations (0-1000 nM) of ergosterol and incubated for different time periods (0-24 h). Intracellular metabolites were extracted with two methods: a selective dispersive liquid-liquid micro-extraction and a general methanol extraction. Chromatographic techniques (GC-FID, GC-MS, GC × GC-TOF-MS, UHPLC-MS) and (1)H NMR spectroscopy were used for quantitative and qualitative analyses. Multivariate data analyses (PCA and OPLS-DA models) were used to extract interpretable information from the multidimensional data generated from the analytical techniques. The results showed that ergosterol triggered differential changes in the metabolome of the cells, leading to variation in the biosynthesis of secondary metabolites. PCA scores plots revealed dose- and time-dependent metabolic variations, with optimal treatment conditions being found to be 300 nM ergosterol and an 18 h incubation period. The observed ergosterol-induced metabolic changes were correlated with changes in defence-related metabolites. The 'defensome' involved increases in terpenoid metabolites with five antimicrobial compounds (the bicyclic sesquiterpenoid phytoalexins: phytuberin, solavetivone, capsidiol, lubimin and rishitin) and other metabolites (abscisic acid and phytosterols) putatively identified. In addition, various phenylpropanoid precursors, cinnamic acid derivatives and - conjugates, coumarins and lignin monomers were annotated. These annotated metabolites revealed a dynamic reprogramming of metabolic networks that are functionally correlated, with a high complexity in their regulation. PMID:24498209

  18. Dynamic signal processing by ribozyme-mediated RNA circuits to control gene expression

    PubMed Central

    Shen, Shensi; Rodrigo, Guillermo; Prakash, Satya; Majer, Eszter; Landrain, Thomas E.; Kirov, Boris; Daròs, José-Antonio; Jaramillo, Alfonso

    2015-01-01

    Organisms have different circuitries that allow converting signal molecule levels to changes in gene expression. An important challenge in synthetic biology involves the de novo design of RNA modules enabling dynamic signal processing in live cells. This requires a scalable methodology for sensing, transmission, and actuation, which could be assembled into larger signaling networks. Here, we present a biochemical strategy to design RNA-mediated signal transduction cascades able to sense small molecules and small RNAs. We design switchable functional RNA domains by using strand-displacement techniques. We experimentally characterize the molecular mechanism underlying our synthetic RNA signaling cascades, show the ability to regulate gene expression with transduced RNA signals, and describe the signal processing response of our systems to periodic forcing in single live cells. The engineered systems integrate RNA–RNA interaction with available ribozyme and aptamer elements, providing new ways to engineer arbitrary complex gene circuits. PMID:25916845

  19. EMD-Based Symbolic Dynamic Analysis for the Recognition of Human and Nonhuman Pyroelectric Infrared Signals.

    PubMed

    Zhao, Jiaduo; Gong, Weiguo; Tang, Yuzhen; Li, Weihong

    2016-01-01

    In this paper, we propose an effective human and nonhuman pyroelectric infrared (PIR) signal recognition method to reduce PIR detector false alarms. First, using the mathematical model of the PIR detector, we analyze the physical characteristics of the human and nonhuman PIR signals; second, based on the analysis results, we propose an empirical mode decomposition (EMD)-based symbolic dynamic analysis method for the recognition of human and nonhuman PIR signals. In the proposed method, first, we extract the detailed features of a PIR signal into five symbol sequences using an EMD-based symbolization method, then, we generate five feature descriptors for each PIR signal through constructing five probabilistic finite state automata with the symbol sequences. Finally, we use a weighted voting classification strategy to classify the PIR signals with their feature descriptors. Comparative experiments show that the proposed method can effectively classify the human and nonhuman PIR signals and reduce PIR detector's false alarms. PMID:26805837

  20. Dynamic signal processing by ribozyme-mediated RNA circuits to control gene expression.

    PubMed

    Shen, Shensi; Rodrigo, Guillermo; Prakash, Satya; Majer, Eszter; Landrain, Thomas E; Kirov, Boris; Daròs, José-Antonio; Jaramillo, Alfonso

    2015-05-26

    Organisms have different circuitries that allow converting signal molecule levels to changes in gene expression. An important challenge in synthetic biology involves the de novo design of RNA modules enabling dynamic signal processing in live cells. This requires a scalable methodology for sensing, transmission, and actuation, which could be assembled into larger signaling networks. Here, we present a biochemical strategy to design RNA-mediated signal transduction cascades able to sense small molecules and small RNAs. We design switchable functional RNA domains by using strand-displacement techniques. We experimentally characterize the molecular mechanism underlying our synthetic RNA signaling cascades, show the ability to regulate gene expression with transduced RNA signals, and describe the signal processing response of our systems to periodic forcing in single live cells. The engineered systems integrate RNA-RNA interaction with available ribozyme and aptamer elements, providing new ways to engineer arbitrary complex gene circuits. PMID:25916845

  1. EMD-Based Symbolic Dynamic Analysis for the Recognition of Human and Nonhuman Pyroelectric Infrared Signals

    PubMed Central

    Zhao, Jiaduo; Gong, Weiguo; Tang, Yuzhen; Li, Weihong

    2016-01-01

    In this paper, we propose an effective human and nonhuman pyroelectric infrared (PIR) signal recognition method to reduce PIR detector false alarms. First, using the mathematical model of the PIR detector, we analyze the physical characteristics of the human and nonhuman PIR signals; second, based on the analysis results, we propose an empirical mode decomposition (EMD)-based symbolic dynamic analysis method for the recognition of human and nonhuman PIR signals. In the proposed method, first, we extract the detailed features of a PIR signal into five symbol sequences using an EMD-based symbolization method, then, we generate five feature descriptors for each PIR signal through constructing five probabilistic finite state automata with the symbol sequences. Finally, we use a weighted voting classification strategy to classify the PIR signals with their feature descriptors. Comparative experiments show that the proposed method can effectively classify the human and nonhuman PIR signals and reduce PIR detector’s false alarms. PMID:26805837

  2. Dynamic shim updating (DSU) for multislice signal acquisition.

    PubMed

    de Graaf, Robin A; Brown, Peter B; McIntyre, Scott; Rothman, Douglas L; Nixon, Terence W

    2003-03-01

    Dynamic shim updating (DSU) is a technique for achieving optimal magnetic field homogeneity over extended volumes by dynamically updating an optimal shim setting for each individual slice in a multislice acquisition protocol. Here the practical implementation of DSU using all first- and second-order shims is described. In particular, the hardware modifications and software requirements are demonstrated. Furthermore, the temporal effects of dynamically switching shim currents are investigated and a Z(2)-to-Z(0) compensation unit is described and implemented to counteract the temporal Z(0) variations following a change in the Z(2) shim current. The optimal shim settings for all slices are determined with a quantitative and user-independent, multislice phase-mapping sequence. The performance of DSU is evaluated from multislice phase maps and spectroscopic images acquired on rat brain in vivo. DSU improved the magnetic field homogeneity over all spatial slices, with a more pronounced effect on the slices positioned away from the magnet isocenter, thereby making the magnetic field homogeneity highly uniform over an extended volume. PMID:12594742

  3. Hemocompatibility evaluation with experimental and computational fluid dynamic analyses for a monopivot circulatory assist pump.

    PubMed

    Nishida, Masahiro; Maruyama, Osamu; Kosaka, Ryo; Yamane, Takashi; Kogure, Hisato; Kawamura, Hiroshi; Yamamoto, Yoshihiro; Kuwana, Katsuyuki; Sankai, Yoshiyuki; Tsutsui, Tatsuo

    2009-04-01

    The hemocompatibility of a newly developed monopivot circulatory assist pump was evaluated by the computational fluid dynamic (CFD) analyses with the particle tracking velocimetry measurement. Results were compared with those of the hemolysis test and in vitro antithrombogenic test to prevent hemolysis and thrombus formation inside the pump. The results of the CFD analysis and the particle tracking velocimetry had a good agreement with each other. The flow distributions by the CFD analysis indicated that the radial jet out of the impeller was adequately weak so that the wall shear stress was lower than 300 Pa on the volute casing wall. It corresponded with the hemolysis tests results, indicating that the hemolysis level was lower than that of the commercially available pump. However, the flow distributions also indicated that the pivot that was easy to stagnate was washed out, not only by the secondary flow through the back gap of the impeller, but also by the vortices generated by the secondary vanes. It corresponded with the in vitro antithrombogenic test results, indicating that thrombus formation could be removed only by redesigning the geometry of the secondary vanes. PMID:19335415

  4. The dynamics of spatio-temporal Rho GTPase signaling: formation of signaling patterns

    PubMed Central

    Fritz, Rafael Dominik; Pertz, Olivier

    2016-01-01

    Rho GTPases are crucial signaling molecules that regulate a plethora of biological functions. Traditional biochemical, cell biological, and genetic approaches have founded the basis of Rho GTPase biology. The development of biosensors then allowed measuring Rho GTPase activity with unprecedented spatio-temporal resolution. This revealed that Rho GTPase activity fluctuates on time and length scales of tens of seconds and micrometers, respectively. In this review, we describe Rho GTPase activity patterns observed in different cell systems. We then discuss the growing body of evidence that upstream regulators such as guanine nucleotide exchange factors and GTPase-activating proteins shape these patterns by precisely controlling the spatio-temporal flux of Rho GTPase activity. Finally, we comment on additional mechanisms that might feed into the regulation of these signaling patterns and on novel technologies required to dissect this spatio-temporal complexity. PMID:27158467

  5. Dynamical system modeling via signal reduction and neural network simulation

    SciTech Connect

    Paez, T.L.; Hunter, N.F.

    1997-11-01

    Many dynamical systems tested in the field and the laboratory display significant nonlinear behavior. Accurate characterization of such systems requires modeling in a nonlinear framework. One construct forming a basis for nonlinear modeling is that of the artificial neural network (ANN). However, when system behavior is complex, the amount of data required to perform training can become unreasonable. The authors reduce the complexity of information present in system response measurements using decomposition via canonical variate analysis. They describe a method for decomposing system responses, then modeling the components with ANNs. A numerical example is presented, along with conclusions and recommendations.

  6. Analyses of the soil surface dynamic of South African Kalahari salt pans based on hyperspectral and multitemporal data

    NASA Astrophysics Data System (ADS)

    Milewski, Robert; Chabrillat, Sabine; Behling, Robert; Mielke, Christian; Schleicher, Anja Maria; Guanter, Luis

    2016-04-01

    The consequences of climate change represent a major threat to sustainable development and growth in Southern Africa. Understanding the impact on the geo- and biosphere is therefore of great importance in this particular region. In this context the Kalahari salt pans (also known as playas or sabkhas) and their peripheral saline and alkaline habitats are an ecosystem of major interest. They are very sensitive to environmental conditions, and as thus hydrological, mineralogical and ecological responses to climatic variations can be analysed. Up to now the soil composition of salt pans in this area have been only assessed mono-temporally and on a coarse regional scale. Furthermore, the dynamic of the salt pans, especially the formation of evaporites, is still uncertain and poorly understood. High spectral resolution remote sensing can estimate evaporite content and mineralogy of soils based on the analyses of the surface reflectance properties within the Visible-Near InfraRed (VNIR 400-1000 nm) and Short-Wave InfraRed (SWIR 1000-2500 nm) regions. In these wavelength regions major chemical components of the soil interact with the electromagnetic radiation and produce characteristic absorption features that can be used to derive the properties of interest. Although such techniques are well established for the laboratory and field scale, the potential of current (Hyperion) and upcoming spaceborne sensors such as EnMAP for quantitative mineralogical and salt spectral mapping is still to be demonstrated. Combined with hyperspectral methods, multitemporal remote sensing techniques allow us to derive the recent dynamic of these salt pans and link the mineralogical analysis of the pan surface to major physical processes in these dryland environments. In this study we focus on the analyses of the Namibian Omongwa salt pans based on satellite hyperspectral imagery and multispectral time-series data. First, a change detection analysis is applied using the Iterative

  7. Plasmodesmata dynamics are coordinated by intracellular signaling pathways

    PubMed Central

    Brunkard, Jacob O.; Runkel, Anne M.; Zambryski, Patricia C.

    2013-01-01

    Membrane-lined channels called plasmodesmata (PD) connect the cytoplasts of adjacent plant cells across the cell wall, permitting intercellular movement of small molecules, proteins, and RNA. Recent genetic screens for mutants with altered PD transport identified genes suggesting that chloroplasts play crucial roles in coordinating PD transport. Complementing this discovery, studies manipulating expression of PD-localized proteins imply that changes in PD transport strongly impact chloroplast biology. Ongoing efforts to find genes that control root and stomatal development reveal the critical role of PD in enforcing tissue patterning, and newly discovered PD-localized proteins show that PD influence development, intracellular signaling, and defense against pathogens. Together, these studies demonstrate that PD function and formation are tightly integrated with plant physiology. PMID:23978390

  8. Inferring causal metabolic signals that regulate the dynamic TORC1-dependent transcriptome

    PubMed Central

    Oliveira, Ana Paula; Dimopoulos, Sotiris; Busetto, Alberto Giovanni; Christen, Stefan; Dechant, Reinhard; Falter, Laura; Haghir Chehreghani, Morteza; Jozefczuk, Szymon; Ludwig, Christina; Rudroff, Florian; Schulz, Juliane Caroline; González, Asier; Soulard, Alexandre; Stracka, Daniele; Aebersold, Ruedi; Buhmann, Joachim M; Hall, Michael N; Peter, Matthias; Sauer, Uwe; Stelling, Jörg

    2015-01-01

    Cells react to nutritional cues in changing environments via the integrated action of signaling, transcriptional, and metabolic networks. Mechanistic insight into signaling processes is often complicated because ubiquitous feedback loops obscure causal relationships. Consequently, the endogenous inputs of many nutrient signaling pathways remain unknown. Recent advances for system-wide experimental data generation have facilitated the quantification of signaling systems, but the integration of multi-level dynamic data remains challenging. Here, we co-designed dynamic experiments and a probabilistic, model-based method to infer causal relationships between metabolism, signaling, and gene regulation. We analyzed the dynamic regulation of nitrogen metabolism by the target of rapamycin complex 1 (TORC1) pathway in budding yeast. Dynamic transcriptomic, proteomic, and metabolomic measurements along shifts in nitrogen quality yielded a consistent dataset that demonstrated extensive re-wiring of cellular networks during adaptation. Our inference method identified putative downstream targets of TORC1 and putative metabolic inputs of TORC1, including the hypothesized glutamine signal. The work provides a basis for further mechanistic studies of nitrogen metabolism and a general computational framework to study cellular processes. PMID:25888284

  9. Characterizing the Response of Commercial and Industrial Facilities to Dynamic Pricing Signals from the Utility

    SciTech Connect

    Mathieu, Johanna L.; Gadgil, Ashok J.; Callaway, Duncan S.; Price, Phillip N.; Kiliccote, Sila

    2010-07-01

    We describe a method to generate statistical models of electricity demand from Commercial and Industrial (C&I) facilities including their response to dynamic pricing signals. Models are built with historical electricity demand data. A facility model is the sum of a baseline demand model and a residual demand model; the latter quantifies deviations from the baseline model due to dynamic pricing signals from the utility. Three regression-based baseline computation methods were developed and analyzed. All methods performed similarly. To understand the diversity of facility responses to dynamic pricing signals, we have characterized the response of 44 C&I facilities participating in a Demand Response (DR) program using dynamic pricing in California (Pacific Gas and Electric's Critical Peak Pricing Program). In most cases, facilities shed load during DR events but there is significant heterogeneity in facility responses. Modeling facility response to dynamic price signals is beneficial to the Independent System Operator for scheduling supply to meet demand, to the utility for improving dynamic pricing programs, and to the customer for minimizing energy costs.

  10. Spatio-temporal dynamics of a cell signal pathway with negative feedbacks: the MAPK/ERK pathway.

    PubMed

    Maya-Bernal, José Luis; Ramírez-Santiago, Guillermo

    2016-03-01

    We studied the spatio-temporal dynamics of a cell signal cascade with negative feedback that quantitatively emulates the regulative process that occurs in the Mitogen Activated Protein Kinase/Extracellular Regulated Kinase (MAPK/ERK) pathway. The model consists of a set of six coupled reaction-diffusion equations that describes the dynamics of the six-module pathway. In the basic module the active form of the protein transmits the signal to the next pathway’s module. As suggested by experiments, the model considers that the fifth module's kinase down-regulates the first and third modules. The feedback parameter is defined as, μ(r)( j)= k(kin)5/k(kin)(j), (j = 1, 3). We analysed the pathway's dynamics for μ(r)( j) = 0.10, 1.0, and 10 in the kinetic regimes: i) saturation of both kinases and phosphatases, ii) saturation of the phosphatases and iii) saturation of the kinases. For a regulated pathway the Total Activated Protein Profiles (TAPPs) as a function of time develop a maximum during the transient stage in the three kinetic regimes. These maxima become higher and their positions shift to longer times downstream. This scenario also applies to the TAPP's regulatory kinase that sums up its inhibitory action to that of the phosphatases leading to a maximum. Nevertheless, when μ(r)(j)= 1.0 , the TAPPs develop two maxima, with the second maximum being almost imperceptible. These results are in qualitative agreement with experimental data obtained from NIH 3T3 mouse fibroblasts. In addition, analyses of the stationary states as a function of position indicate that in the kinetic regime i) which is of physiological interest, signal transduction occurs with a relatively large propagation length for the three values of the regulative parameter. However, for μ(r)(j)= 0.10 , the sixth module concentration profile is transmitted with approximately 45% of its full value. The results obtained for μ(r)(j) = 10 , indicate that the first five concentration profiles are

  11. A divergent canonical WNT-signaling pathway regulates microtubule dynamics

    PubMed Central

    Ciani, Lorenza; Krylova, Olga; Smalley, Matthew J.; Dale, Trevor C.; Salinas, Patricia C.

    2004-01-01

    Dishevelled (DVL) is associated with axonal microtubules and regulates microtubule stability through the inhibition of the serine/threonine kinase, glycogen synthase kinase 3β (GSK-3β). In the canonical WNT pathway, the negative regulator Axin forms a complex with β-catenin and GSK-3β, resulting in β-catenin degradation. Inhibition of GSK-3β by DVL increases β-catenin stability and TCF transcriptional activation. Here, we show that Axin associates with microtubules and unexpectedly stabilizes microtubules through DVL. In turn, DVL stabilizes microtubules by inhibiting GSK-3β through a transcription- and β-catenin–independent pathway. More importantly, axonal microtubules are stabilized after DVL localizes to axons. Increased microtubule stability is correlated with a decrease in GSK-3β–mediated phosphorylation of MAP-1B. We propose a model in which Axin, through DVL, stabilizes microtubules by inhibiting a pool of GSK-3β, resulting in local changes in the phosphorylation of cellular targets. Our data indicate a bifurcation in the so-called canonical WNT-signaling pathway to regulate microtubule stability. PMID:14734535

  12. Dynamical analyses of the companions orbiting eclipsing binaries - I. SW Lacertae

    NASA Astrophysics Data System (ADS)

    Yuan, Jinzhao; Şenavci, Hakan Volkan

    2014-03-01

    New mid-eclipse times of the short-period eclipsing binary SW Lacertae are reported, and two cyclical variations are found in the corresponding O - C diagram. The proposed light-travel time model is refined. The best fit suggests that two possible circumbinary companions are in a near 3:1 mean-motion resonance with periods of 27.01 and 82.61 yr. Based on the best-fitting solution, we have studied the stabilities of the two companions moving on a series of mutually inclined orbits. The results show that no orbital configurations can survive for >1000 yr. Then, non-Keplerian corrections to the initial conditions and the more distant K-dwarf companion discovered by Ruciński, Pribulla & van Kerkwijk, moving on assumed circular orbits with wide ranges of orbital inclinations, are considered in our numerical simulations. The outcome similarly reveals that the whole system is yet short-term unstable. Perhaps, one or both cyclical variations in the mid-eclipse times are attributed to irregular mass exchange and/or magnetic cycles in the magnetically active W UMa system. Despite this, the instability of the system may also arise from the large uncertainties in orbital parameters. So, secular observations of this target are needed to determine the eccentricity of the outmost companion and the orbital period of the middle companion with much higher precision. Our results suggest that, if the two inner companions do exist, they should be on mutually inclined orbits of >100°, with the minimum masses of 0.62 and 1.94 M⊙ for the innermost and middle components, respectively. Our work demonstrates that it is important and necessary to perform dynamical analyses before a discovery of two or more circumbinary companions is announced.

  13. Dynamics of the 2014 Holuhraun fissure eruption analysed by video monitoring system

    NASA Astrophysics Data System (ADS)

    Witt, Tanja; Walter, Thomas R.

    2015-04-01

    Events on the volcanic system within the axial volcanic zones are linked to plate movements. The spreading and subsequent rifting of the crust take place at the plate boundary and occurs in distinct rifting episodes. These rifting episodes are characterized by earthquakes and volcanic eruptions within the central volcano or along fissures. For the subsurface structure of a volcanic system and the behavior of the magma plumbing system during major rifting episodes two contrasting models exists, (i) vertical feeding by a deep magma source or (ii) lateral feeding through a shallow magma chamber under the central volcano. The ongoing 2014 Holuhraun eruption is providing a unique opportunity to rigorously test the feeding paths of an active fissure eruption. Here we employ video images to analyse the height and velocity variation of the lava fountains at the Holuhraun eruption fissure. On the first day of the eruption we could set up in total five high resolution video cameras. With algorithms of photogrammetry and correlation analysis we interpret the behavior of the lava fountains. Results suggest a significal lateral propagation path of the dynamics of the active vents, and a lateral migration of the peaks and lows of distinct lava fountains. Although the correlation system can change episodically and sporadically, both the frequency of the lava fountains and the eruption and rest time between single fountains remain similar for adjacent lava fountains imply a controlling process in the magma feeder system itself. We interpret the results by a lateral magma and gas flow underlying and feeding the eruption fissure. Systematic recording and analysis of video data hence help to decide which magma plumbing system is more reliable. Additionally, the dataset allows us to compare the eruption behavior to seismic datasets.

  14. Investigating carbon dynamics in Siberian peat bogs using molecular-level analyses

    NASA Astrophysics Data System (ADS)

    Kaiser, K.; Benner, R. H.

    2013-12-01

    Total hydrolysable carbohydrates, and lignin and cutin acid compounds were analyzed in peat cores collected 56.8 N (SIB04), 58.4 N (SIB06), 63.8 N (G137) and 66.5 N (E113) in the Western Siberian Lowland to investigate vegetation, chemical compositions and the stage of decomposition. Sphagnum mosses dominated peatland vegetation in all four cores. High-resolution molecular analyses revealed rapid vegetation changes on timescales of 50-200 years in the southern cores Sib4 and Sib6. Syringyl and vanillyl (S/V) ratios and cutin acids indicated these vegetation changes were due to varying inputs of angiosperm and gymnosperm and root material. In the G137 and E113 cores lichens briefly replaced sphagnum mosses and vascular plants. Molecular decomposition indicators used in this study tracked the decomposition of different organic constituents of peat organic matter. The carbohydrate decomposition index was sensitive to the polysaccharide component of all peat-forming plants, whereas acid/aldehyde ratios of S and V phenols (Ac/AlS,V) followed the lignin component of vascular plants. Low carbohydrate decomposition indices in peat layers corresponded well with elevated (Ad/Al)S,V ratios. This suggested both classes of biochemicals were simultaneously decomposed, and decomposition processes were associated with extensive total mass loss in these ombrotrophic systems. Selective decomposition or transformation of lignin was observed in the permafrost-influenced northern cores G137 and E113. Both cores exhibited the highest (Ad/Al)S,V ratios, almost four-fold higher than measured in peat-forming plants. The extent of decomposition in the four peat cores did not uniformly increase with age, but showed episodic extensive decomposition events. Variable decomposition events independent of climatic conditions and vegetation shifts highlight the complexity of peatland dynamics.

  15. Reliability of Corneal Dynamic Scheimpflug Analyser Measurements in Virgin and Post-PRK Eyes

    PubMed Central

    Chen, Xiangjun; Stojanovic, Aleksandar; Hua, Yanjun; Eidet, Jon Roger; Hu, Di; Wang, Jingting; Utheim, Tor Paaske

    2014-01-01

    Purpose To determine the measurement reliability of CorVis ST, a dynamic Scheimpflug analyser, in virgin and post-photorefractive keratectomy (PRK) eyes and compare the results between these two groups. Methods Forty virgin eyes and 42 post-PRK eyes underwent CorVis ST measurements performed by two technicians. Repeatability was evaluated by comparing three consecutive measurements by technician A. Reproducibility was determined by comparing the first measurement by technician A with one performed by technician B. Intraobserver and interobserver intraclass correlation coefficients (ICCs) were calculated. Univariate analysis of covariance (ANCOVA) was used to compare measured parameters between virgin and post-PRK eyes. Results The intraocular pressure (IOP), central corneal thickness (CCT) and 1st applanation time demonstrated good intraobserver repeatability and interobserver reproducibility (ICC≧0.90) in virgin and post-PRK eyes. The deformation amplitude showed a good or close to good repeatability and reproducibility in both groups (ICC≧0.88). The CCT correlated positively with 1st applanation time (r = 0.437 and 0.483, respectively, p<0.05) and negatively with deformation amplitude (r = −0.384 and −0.375, respectively, p<0.05) in both groups. Compared to post-PRK eyes, virgin eyes showed longer 1st applanation time (7.29±0.21 vs. 6.96±0.17 ms, p<0.05) and lower deformation amplitude (1.06±0.07 vs. 1.17±0.08 mm, p<0.05). Conclusions CorVis ST demonstrated reliable measurements for CCT, IOP, and 1st applanation time, as well as relatively reliable measurement for deformation amplitude in both virgin and post-PRK eyes. There were differences in 1st applanation time and deformation amplitude between virgin and post-PRK eyes, which may reflect corneal biomechanical changes occurring after the surgery in the latter. PMID:25302580

  16. Variability analyses suggest that supraspino-spinal interactions provide dynamic stability in motor control.

    PubMed

    Wang, H; Jung, R

    2002-03-15

    Effects of supraspino-spinal feedforward-feedback (FF-FB) interactions on variability in locomotor rhythm and coordination were examined in in vitro brain-spinal cord lamprey preparations. Spinal locomotor networks were activated by applying 0.2 mM N-methyl-DL-aspartate (NMA) to three spinal pools: gill, rostral and caudal. Bathing the brain with zero Ca(2+) saline altered supraspinal-spinal drive and FF-FB interaction while spino-supraspinal feedback was changed by applying NMA to the caudal pool only. Wavelet analyses indicated a non-uniform energy distribution in ventral root (VR) activity that shifted between frequency bands on FF-FB interruption. Wavelet analysis was used to extract 300-s long epochs of low frequency burst rhythm. These were analyzed using a sliding-window time-varying covariance method. From the autocovariance in each window, the cycle period and height of the first side lobe peak were determined. Rostral VR variability (determined from standard deviation and coefficient of variation of all cycle periods and the mean peak height) was significantly higher than caudal VR variability. FF-FB interruption significantly decreased the rostral VR cycle period and variability but the rostro-caudal gradient remained. The intersegmental delay was also affected. The caudal VR rhythm with NMA in the caudal pool only was slower but more variable than with NMA over the entire cord. These results indicate that the locomotor rhythm in the presence of supraspino-spinal interactions is slower but has a higher variability. The higher variability may reflect a dynamic stability of the system. Additionally, differences in local neural organization likely contribute to rostro-caudal differences in variability of the motor output. PMID:11879799

  17. Photoinduced bulk-surface dynamics: time resolved two photon photoemission signals at semiconductor surfaces

    NASA Astrophysics Data System (ADS)

    Ramakrishna, S.; Willig, F.; Knorr, A.

    2004-06-01

    A free particle theory of photoinduced bulk-surface dynamics at semiconductor surfaces is developed wherein relaxation processes arising from electron-electron and electron-phonon scattering are treated phenomenologically. The role played by bulk-surface dynamics in the thermalization and cooling processes of the bulk and the complementary issue of how bulk dynamics influences the surface state occupancy are both studied. Time resolved 2PPE spectra is analysed both in the context of pure bulk as well as combined bulk-surface dynamics and its relation to the time dependent populations in the conduction band and surface states is discussed.

  18. Dynamics of the actin cytoskeleton mediates receptor cross talk: An emerging concept in tuning receptor signaling

    PubMed Central

    Mattila, Pieta K.; Batista, Facundo D.

    2016-01-01

    Recent evidence implicates the actin cytoskeleton in the control of receptor signaling. This may be of particular importance in the context of immune receptors, such as the B cell receptor, where dysregulated signaling can result in autoimmunity and malignancy. Here, we discuss the role of the actin cytoskeleton in controlling receptor compartmentalization, dynamics, and clustering as a means to regulate receptor signaling through controlling the interactions with protein partners. We propose that the actin cytoskeleton is a point of integration for receptor cross talk through modulation of protein dynamics and clustering. We discuss the implication of this cross talk via the cytoskeleton for both ligand-induced and low-level constitutive (tonic) signaling necessary for immune cell survival. PMID:26833785

  19. Signal processing for determining water height in steam pipes with dynamic surface conditions

    NASA Astrophysics Data System (ADS)

    Lih, Shyh-Shiuh; Lee, Hyeong Jae; Bar-Cohen, Yoseph

    2015-03-01

    An enhanced signal processing method based on the filtered Hilbert envelope of the auto-correlation function of the wave signal has been developed to monitor the height of condensed water through the steel wall of steam pipes with dynamic surface conditions. The developed signal processing algorithm can also be used to estimate the thickness of the pipe to determine the cut-off frequency for the low pass filter frequency of the Hilbert Envelope. Testing and analysis results by using the developed technique for dynamic surface conditions are presented. A multiple array of transducers setup and methodology are proposed for both the pulse-echo and pitch-catch signals to monitor the fluctuation of the water height due to disturbance, water flow, and other anomaly conditions.

  20. Electrical Motor Current Signal Analysis using a Dynamic Time Warping Method for Fault Diagnosis

    NASA Astrophysics Data System (ADS)

    Zhen, D.; Alibarbar, A.; Zhou, X.; Gu, F.; Ball, A. D.

    2011-07-01

    This paper presents the analysis of phase current signals to identify and quantify common faults from an electrical motor based on dynamic time warping (DTW) algorithm. In condition monitoring, measurements are often taken when the motor undertakes varying loads and speeds. The signals acquired in these conditions show similar profiles but have phase shifts, which do not line up in the time-axis for adequate comparison to discriminate the small changes in machine health conditions. In this study, DTW algorithms are exploited to align the signals to an ideal current signal constructed based on average operating conditions. In this way, comparisons between the signals can be made directly in the time domain to obtain residual signals. These residual signals are then based on to extract features for detecting and diagnosing the faults of the motor and components operating under different loads and speeds. This study provides a novel approach to the analysis of electrical current signal for diagnosis of motor faults. Experimental data sets of electrical motor current signals have been studied using DTW algorithms. Results show that DTW based residual signals highlights more the modulations due to the compressor process. And hence can obtain better fault detection and diagnosis results.

  1. Capabilities and applications of a computer program system for dynamic loads analyses of flexible airplanes with active controls /DYLOFLEX/

    NASA Technical Reports Server (NTRS)

    Perry, B., III; Goetz, R. C.; Kroll, R. I.; Miller, R. D.

    1979-01-01

    This paper describes and illustrates the capabilities of the DYLOFLEX Computer Program System. DYLOFLEX is an integrated system of computer programs for calculating dynamic loads of flexible airplanes with active control systems. A brief discussion of the engineering formulation for each of the nine DYLOFLEX programs is described. The capabilities of the system are illustrated by the analyses of two example configurations.

  2. Dynamic Range Enhancement of High-Speed Electrical Signal Data via Non-Linear Compression

    NASA Technical Reports Server (NTRS)

    Laun, Matthew C. (Inventor)

    2016-01-01

    Systems and methods for high-speed compression of dynamic electrical signal waveforms to extend the measuring capabilities of conventional measuring devices such as oscilloscopes and high-speed data acquisition systems are discussed. Transfer function components and algorithmic transfer functions can be used to accurately measure signals that are within the frequency bandwidth but beyond the voltage range and voltage resolution capabilities of the measuring device.

  3. MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling.

    PubMed

    Ka, Minhan; Jung, Eui-Man; Mueller, Ulrich; Kim, Woo-Yang

    2014-11-01

    Neuronal migration and subsequent differentiation play critical roles for establishing functional neural circuitry in the developing brain. However, the molecular mechanisms that regulate these processes are poorly understood. Here, we show that microtubule actin crosslinking factor 1 (MACF1) determines neuronal positioning by regulating microtubule dynamics and mediating GSK-3 signaling during brain development. First, using MACF1 floxed allele mice and in utero gene manipulation, we find that MACF1 deletion suppresses migration of cortical pyramidal neurons and results in aberrant neuronal positioning in the developing brain. The cell autonomous deficit in migration is associated with abnormal dynamics of leading processes and centrosomes. Furthermore, microtubule stability is severely damaged in neurons lacking MACF1, resulting in abnormal microtubule dynamics. Finally, MACF1 interacts with and mediates GSK-3 signaling in developing neurons. Our findings establish a cellular mechanism underlying neuronal migration and provide insights into the regulation of cytoskeleton dynamics in developing neurons. PMID:25224226

  4. Regulation of branching dynamics by axon-intrinsic asymmetries in Tyrosine Kinase Receptor signaling

    PubMed Central

    Zschätzsch, Marlen; Oliva, Carlos; Langen, Marion; De Geest, Natalie; Özel, Mehmet Neset; Williamson, W Ryan; Lemon, William C; Soldano, Alessia; Munck, Sebastian; Hiesinger, P Robin; Sanchez-Soriano, Natalia; Hassan, Bassem A

    2014-01-01

    Axonal branching allows a neuron to connect to several targets, increasing neuronal circuit complexity. While axonal branching is well described, the mechanisms that control it remain largely unknown. We find that in the Drosophila CNS branches develop through a process of excessive growth followed by pruning. In vivo high-resolution live imaging of developing brains as well as loss and gain of function experiments show that activation of Epidermal Growth Factor Receptor (EGFR) is necessary for branch dynamics and the final branching pattern. Live imaging also reveals that intrinsic asymmetry in EGFR localization regulates the balance between dynamic and static filopodia. Elimination of signaling asymmetry by either loss or gain of EGFR function results in reduced dynamics leading to excessive branch formation. In summary, we propose that the dynamic process of axon branch development is mediated by differential local distribution of signaling receptors. DOI: http://dx.doi.org/10.7554/eLife.01699.001 PMID:24755286

  5. Requirements for implementation of Kuessner and Wagner indicial lift growth functions into the FLEXSTAB computer program system for use in dynamic loads analyses

    NASA Technical Reports Server (NTRS)

    Miller, R. D.; Rogers, J. T.

    1975-01-01

    General requirements for dynamic loads analyses are described. The indicial lift growth function unsteady subsonic aerodynamic representation is reviewed, and the FLEXSTAB CPS is evaluated with respect to these general requirements. The effects of residual flexibility techniques on dynamic loads analyses are also evaluated using a simple dynamic model.

  6. Context-dependent dynamic UV signaling in female three spine sticklebacks

    PubMed Central

    Hiermes, Meike; Bakker, Theo C. M.; Mehlis, Marion; Rick, Ingolf P.

    2015-01-01

    Color signals, including ultraviolet (UV) signals, are widespread throughout the animal kingdom and color changes can be influenced by reproductive and motivational state. However, studies on dynamic changes of UV signals are scarce. Three spine sticklebacks (Gasterosteus aculeatus) that show intraspecific UV communication were used to study dynamic UV signaling in females. Reflectance measurements were taken from the distended abdomen, which serves as signal of female fecundity and readiness to spawn for courting males, and the melanized dorsal region. Scans were taken during egg maturation as well as before and after stimulation with a male to investigate context-dependent color changes. We used a physiological model of vision to determine how females might be perceived by conspecifics and quantified chromatic contrasts among both body regions and between body regions and the background for all stages. Females showed a significant increase in abdominal UV intensity during egg maturation and in response to a courting male. Measures of chromatic contrast among body regions (abdomen vs. dorsal region) and against the background (abdomen vs. background) were also increased during egg maturation and in response to the male stimulus (abdomen vs. background). Our results provide evidence for dynamic UV signaling in females in a reproductive context. PMID:26658986

  7. Signaling and Adaptation Modulate the Dynamics of the Photosensoric Complex of Natronomonas pharaonis

    PubMed Central

    Mulkidjanian, Armen Y.; Shaitan, Konstantin V.; Engelhard, Martin; Klare, Johann P.; Steinhoff, Heinz-Jürgen

    2015-01-01

    Motile bacteria and archaea respond to chemical and physical stimuli seeking optimal conditions for survival. To this end transmembrane chemo- and photoreceptors organized in large arrays initiate signaling cascades and ultimately regulate the rotation of flagellar motors. To unravel the molecular mechanism of signaling in an archaeal phototaxis complex we performed coarse-grained molecular dynamics simulations of a trimer of receptor/transducer dimers, namely NpSRII/NpHtrII from Natronomonas pharaonis. Signaling is regulated by a reversible methylation mechanism called adaptation, which also influences the level of basal receptor activation. Mimicking two extreme methylation states in our simulations we found conformational changes for the transmembrane region of NpSRII/NpHtrII which resemble experimentally observed light-induced changes. Further downstream in the cytoplasmic domain of the transducer the signal propagates via distinct changes in the dynamics of HAMP1, HAMP2, the adaptation domain and the binding region for the kinase CheA, where conformational rearrangements were found to be subtle. Overall these observations suggest a signaling mechanism based on dynamic allostery resembling models previously proposed for E. coli chemoreceptors, indicating similar properties of signal transduction for archaeal photoreceptors and bacterial chemoreceptors. PMID:26496122

  8. Laser dynamical reservoir computing with consistency: an approach of a chaos mask signal.

    PubMed

    Nakayama, Joma; Kanno, Kazutaka; Uchida, Atsushi

    2016-04-18

    We numerically investigate reservoir computing based on the consistency of a semiconductor laser subjected to optical feedback and injection. We introduce a chaos mask signal as an input temporal mask for reservoir computing and perform a time-series prediction task. We compare the errors of the task obtained from the chaos mask signal with those obtained from other digital and analog masks. The performance of the prediction task can be improved by using the chaos mask signal due to complex dynamical response. PMID:27137303

  9. Predicting the evolutionary dynamic behavior of a laser with injected signal using Lyapunov exponents

    NASA Astrophysics Data System (ADS)

    Bandy, D. K.; Hall, J. R.; Denker, M. E.

    2015-07-01

    We show that the role of the Lyapunov exponents can be extended beyond the customary local instability, such as limit cycle behavior, to include its use as an evolutionary predictor of the dynamics of a laser with injected signal (LIS). Numerical studies of LIS reveal that as a function of the input-signal strength the evolution of two nonzero Lyapunov exponents (generally equal) distinctively predicts the evolutionary trend of the fundamental frequency of the laser output signal (an important dynamic characteristic of the LIS) even with the presence of some noise. This globally predictive behavior of the Lyapunov exponents includes also the dynamic behavior of the individual coexisting attractors. Different coexisting attractors of LIS and configurations of Lyapunov exponents for both individual attractors and the global system are reported. Two LIS case studies are considered: (I) a high-gain system with a rich history of nonlinear behavior but not experimentally accessible, and (II) a low-gain system that has complex dynamics and is experimentally accessible for Class B lasers. Universality arguments support the thesis that these different configurations and the extended role of the Lyapunov exponents as an evolutionary predictor of the dynamics will be observed in other nonlinear, dynamic dissipative systems as well.

  10. Co-evolutionary Dynamics of Collective Action with Signaling for a Quorum

    PubMed Central

    Pacheco, Jorge M.; Vasconcelos, Vítor V.; Santos, Francisco C.; Skyrms, Brian

    2015-01-01

    Collective signaling for a quorum is found in a wide range of organisms that face collective action problems whose successful solution requires the participation of some quorum of the individuals present. These range from humans, to social insects, to bacteria. The mechanisms involved, the quorum required, and the size of the group may vary. Here we address the general question of the evolution of collective signaling at a high level of abstraction. We investigate the evolutionary dynamics of a population engaging in a signaling N-person game theoretic model. Parameter settings allow for loners and cheaters, and for costly or costless signals. We find a rich dynamics, showing how natural selection, operating on a population of individuals endowed with the simplest strategies, is able to evolve a costly signaling system that allows individuals to respond appropriately to different states of Nature. Signaling robustly promotes cooperative collective action, in particular when coordinated action is most needed and difficult to achieve. Two different signaling systems may emerge depending on Nature’s most prevalent states. PMID:25706984

  11. Efficient detection and signal parameter estimation with application to high dynamic GPS receiver

    NASA Technical Reports Server (NTRS)

    Kumar, Rajendra (Inventor)

    1990-01-01

    In a system for deriving position, velocity, and acceleration information from a received signal emitted from an object to be tracked wherein the signal comprises a carrier signal phase modulated by unknown binary data and experiencing very high Doppler and Doppler rate, this invention provides combined estimation/detection apparatus for simultaneously detecting data bits and obtaining estimates of signal parameters such as carrier phase and frequency related to receiver dynamics in a sequential manner. There is a first stage for obtaining estimates of the signal parameters related to phase and frequency in the vicinity of possible data transitions on the basis of measurements obtained within a current data bit. A second stage uses the estimates from the first stage to decide whether or not a data transition has actually occurred. There is a third stage for removing data modulation from the received signal when a data transition has occurred and a fourth stage for using the received signal with data modulation removed therefrom to update global parameters which are dependent only upon receiver dynamics and independent of data modulation. Finally, there is a fifth stage for using the global parameters to determine the position, velocity, and acceleration of the object.

  12. Epidermal Wnt controls hair follicle induction by orchestrating dynamic signaling crosstalk between the epidermis and dermis.

    PubMed

    Fu, Jiang; Hsu, Wei

    2013-04-01

    A signal first arising in the dermis to initiate the development of hair follicles has been described for many decades. Wnt is the earliest signal known to be intimately involved in hair follicle induction. However, it is not clear whether the inductive signal of Wnt arises intradermally or intraepidermally. Whether Wnt acts as the first dermal signal to initiate hair follicle development also remains unclear. Here we report that Wnt production mediated by Gpr177, the mouse Wls ortholog, is essential for hair follicle induction. Gpr177, encoding a multipass transmembrane protein, regulates Wnt sorting and secretion. Cell type-specific abrogation of the signal reveals that only epidermal, but not dermal, production of Wnt is required. An intraepidermal Wnt signal is necessary and sufficient for hair follicle initiation. However, the subsequent development depends on reciprocal signaling crosstalk of epidermal and dermal cells. Wnt signals within the epidermis and dermis and crossing between the epidermis and dermis have distinct roles and specific functions in skin development. This study not only defines the cell type responsible for Wnt production, but also reveals a highly dynamic regulation of Wnt signaling at different steps of hair follicle morphogenesis. Our findings uncover a mechanism underlying hair follicle development orchestrated by the Wnt pathway. PMID:23190887

  13. Stat5 signaling specifies basal versus stress erythropoietic responses through distinct binary and graded dynamic modalities.

    PubMed

    Porpiglia, Ermelinda; Hidalgo, Daniel; Koulnis, Miroslav; Tzafriri, Abraham R; Socolovsky, Merav

    2012-08-01

    Erythropoietin (Epo)-induced Stat5 phosphorylation (p-Stat5) is essential for both basal erythropoiesis and for its acceleration during hypoxic stress. A key challenge lies in understanding how Stat5 signaling elicits distinct functions during basal and stress erythropoiesis. Here we asked whether these distinct functions might be specified by the dynamic behavior of the Stat5 signal. We used flow cytometry to analyze Stat5 phosphorylation dynamics in primary erythropoietic tissue in vivo and in vitro, identifying two signaling modalities. In later (basophilic) erythroblasts, Epo stimulation triggers a low intensity but decisive, binary (digital) p-Stat5 signal. In early erythroblasts the binary signal is superseded by a high-intensity graded (analog) p-Stat5 response. We elucidated the biological functions of binary and graded Stat5 signaling using the EpoR-HM mice, which express a "knocked-in" EpoR mutant lacking cytoplasmic phosphotyrosines. Strikingly, EpoR-HM mice are restricted to the binary signaling mode, which rescues these mice from fatal perinatal anemia by promoting binary survival decisions in erythroblasts. However, the absence of the graded p-Stat5 response in the EpoR-HM mice prevents them from accelerating red cell production in response to stress, including a failure to upregulate the transferrin receptor, which we show is a novel stress target. We found that Stat5 protein levels decline with erythroblast differentiation, governing the transition from high-intensity graded signaling in early erythroblasts to low-intensity binary signaling in later erythroblasts. Thus, using exogenous Stat5, we converted later erythroblasts into high-intensity graded signal transducers capable of eliciting a downstream stress response. Unlike the Stat5 protein, EpoR expression in erythroblasts does not limit the Stat5 signaling response, a non-Michaelian paradigm with therapeutic implications in myeloproliferative disease. Our findings show how the binary and

  14. Global dynamical modeling of time series and application to restoration of broadband signal characteristics

    SciTech Connect

    Gribkov, D.A.; Gribkova, V.V.; Kuznetsov, Y.I.; Rzhanov, A.G.

    1996-06-01

    We show the principle possibility of the external complex action restoring using the nonlinear dynamics inverse problem solution. It is shown that broadband signal can be restored from the time series of the process generated by nonstationary chaotic system using the reconstructed model as the nonlinear filter. {copyright} {ital 1996 American Institute of Physics.}

  15. Two-Stage Dynamic Signal Detection: A Theory of Choice, Decision Time, and Confidence

    ERIC Educational Resources Information Center

    Pleskac, Timothy J.; Busemeyer, Jerome R.

    2010-01-01

    The 3 most often-used performance measures in the cognitive and decision sciences are choice, response or decision time, and confidence. We develop a random walk/diffusion theory--2-stage dynamic signal detection (2DSD) theory--that accounts for all 3 measures using a common underlying process. The model uses a drift diffusion process to account…

  16. Detection of allosteric signal transmission by information-theoretic analysis of protein dynamics

    PubMed Central

    Pandini, Alessandro; Fornili, Arianna; Fraternali, Franca; Kleinjung, Jens

    2012-01-01

    Allostery offers a highly specific way to modulate protein function. Therefore, understanding this mechanism is of increasing interest for protein science and drug discovery. However, allosteric signal transmission is difficult to detect experimentally and to model because it is often mediated by local structural changes propagating along multiple pathways. To address this, we developed a method to identify communication pathways by an information-theoretical analysis of molecular dynamics simulations. Signal propagation was described as information exchange through a network of correlated local motions, modeled as transitions between canonical states of protein fragments. The method was used to describe allostery in two-component regulatory systems. In particular, the transmission from the allosteric site to the signaling surface of the receiver domain NtrC was shown to be mediated by a layer of hub residues. The location of hubs preferentially connected to the allosteric site was found in close agreement with key residues experimentally identified as involved in the signal transmission. The comparison with the networks of the homologues CheY and FixJ highlighted similarities in their dynamics. In particular, we showed that a preorganized network of fragment connections between the allosteric and functional sites exists already in the inactive state of all three proteins.—Pandini, A., Fornili, A., Fraternali, F., Kleinjung, J. Detection of allosteric signal transmission by information-theoretic analysis of protein dynamics. PMID:22071506

  17. Novel Method for Processing the Dynamic Calibration Signal of Pressure Sensor

    PubMed Central

    Wang, Zhongyu; Li, Qiang; Wang, Zhuoran; Yan, Hu

    2015-01-01

    Dynamic calibration is one of the important ways to acquire the dynamic performance parameters of a pressure sensor. This research focuses on the processing method for the output of calibrated pressure sensor, and mainly attempts to solve the problem of extracting the true information of step response under strong interference noise. A dynamic calibration system based on a shock tube is established to excite the time-domain response signal of a calibrated pressure sensor. A key processing on difference modeling is applied for the obtained signal, and several generating sequences are established. A fusion process for the generating sequences is then undertaken, and the true information of the step response of the calibrated pressure sensor can be obtained. Finally, by implementing the common QR decomposition method to deal with the true information, a dynamic model characterizing the dynamic performance of the calibrated pressure sensor is established. A typical pressure sensor was used to perform calibration tests and a frequency-domain experiment for the sensor was also conducted. Results show that the proposed method could effectively filter strong interference noise in the output of the sensor and the corresponding dynamic model could effectively characterize the dynamic performance of the pressure sensor. PMID:26197324

  18. Novel Method for Processing the Dynamic Calibration Signal of Pressure Sensor.

    PubMed

    Wang, Zhongyu; Li, Qiang; Wang, Zhuoran; Yan, Hu

    2015-01-01

    Dynamic calibration is one of the important ways to acquire the dynamic performance parameters of a pressure sensor. This research focuses on the processing method for the output of calibrated pressure sensor, and mainly attempts to solve the problem of extracting the true information of step response under strong interference noise. A dynamic calibration system based on a shock tube is established to excite the time-domain response signal of a calibrated pressure sensor. A key processing on difference modeling is applied for the obtained signal, and several generating sequences are established. A fusion process for the generating sequences is then undertaken, and the true information of the step response of the calibrated pressure sensor can be obtained. Finally, by implementing the common QR decomposition method to deal with the true information, a dynamic model characterizing the dynamic performance of the calibrated pressure sensor is established. A typical pressure sensor was used to perform calibration tests and a frequency-domain experiment for the sensor was also conducted. Results show that the proposed method could effectively filter strong interference noise in the output of the sensor and the corresponding dynamic model could effectively characterize the dynamic performance of the pressure sensor. PMID:26197324

  19. Clustering of time-evolving scaling dynamics in a complex signal.

    PubMed

    Saghir, Hamidreza; Chau, Tom; Kushki, Azadeh

    2016-07-01

    Complex time series are widespread in physics and physiology. Multifractal analysis provides a tool to study the scaling dynamics of such time series. However, the temporal evolution of scaling dynamics has been ignored by traditional tools such as the multifractal spectrum. We present scaling maps that add the time dimension to the study of scaling dynamics. This is particularly important in cases in which the dynamics of the underlying processes change in time or in applications that necessitate real-time detection of scaling dynamics. In addition, we present a methodology for automatic clustering of existing scaling regimes in a signal. We demonstrate the methodology on time-evolving correlated and uncorrelated noise and the output of a physiological control system (i.e., cardiac interbeat intervals) in healthy and pathological states. PMID:27575136

  20. Clustering of time-evolving scaling dynamics in a complex signal

    NASA Astrophysics Data System (ADS)

    Saghir, Hamidreza; Chau, Tom; Kushki, Azadeh

    2016-07-01

    Complex time series are widespread in physics and physiology. Multifractal analysis provides a tool to study the scaling dynamics of such time series. However, the temporal evolution of scaling dynamics has been ignored by traditional tools such as the multifractal spectrum. We present scaling maps that add the time dimension to the study of scaling dynamics. This is particularly important in cases in which the dynamics of the underlying processes change in time or in applications that necessitate real-time detection of scaling dynamics. In addition, we present a methodology for automatic clustering of existing scaling regimes in a signal. We demonstrate the methodology on time-evolving correlated and uncorrelated noise and the output of a physiological control system (i.e., cardiac interbeat intervals) in healthy and pathological states.

  1. Escaping the flatlands: new approaches to study dynamic assembly and activation of GPCR signaling complexes

    PubMed Central

    Huber, Thomas; Sakmar, Thomas P.

    2011-01-01

    Despite significant recent advances in molecular and structural studies of G protein-coupled receptors (GPCRs), understanding transmembrane signal transduction with chemical precision requires new approaches. Simple binary receptor-ligand or receptor-G protein complex models cannot describe adequately the relevant macromolecular signaling machines. GPCR “signalosomes” undergo complex dynamic assembly/disassembly reactions to create allosteric signaling conduits whose properties cannot necessarily be predicted from individual elements alone. The combinatorial possibilities inherent in a system with hundreds of potential components suggest that high-content miniaturized experimental platforms and computational approaches will be required. To study allosteric effects involved in signalosome reaction pathways, a bottom-up approach is proposed to use multicolor single-molecule detection fluorescence experiments in biochemically defined systems complemented by molecular dynamics models of macromolecular complexes. In bridging the gap between molecular and systems biology, this synthetic approach suggests a way forward from the flatlands to multi-dimensional data collection. PMID:21497404

  2. Proteins move! Protein dynamics and long-range allostery in cell signaling.

    PubMed

    Bu, Zimei; Callaway, David J E

    2011-01-01

    An emerging point of view in protein chemistry is that proteins are not the static objects that are displayed in textbooks but are instead dynamic actors. Protein dynamics plays a fundamental role in many diseases, and spans a large hierarchy of timescales, from picoseconds to milliseconds or even longer. Nanoscale protein domain motion on length scales comparable to protein dimensions is key to understanding how signals are relayed through multiple protein-protein interactions. A canonical example is how the scaffolding proteins NHERF1 and ezrin work in coordination to assemble crucial membrane complexes. As membrane-cytoskeleton scaffolding proteins, these provide excellent prototypes for understanding how regulatory signals are relayed through protein-protein interactions between the membrane and the cytoskeleton. Here, we review recent progress in understanding the structure and dynamics of the interaction. We describe recent novel applications of neutron spin echo spectroscopy to reveal the dynamic propagation of allosteric signals by nanoscale protein motion, and present a guide to the future study of dynamics and its application to the cure of disease. PMID:21570668

  3. MDSINE: Microbial Dynamical Systems INference Engine for microbiome time-series analyses.

    PubMed

    Bucci, Vanni; Tzen, Belinda; Li, Ning; Simmons, Matt; Tanoue, Takeshi; Bogart, Elijah; Deng, Luxue; Yeliseyev, Vladimir; Delaney, Mary L; Liu, Qing; Olle, Bernat; Stein, Richard R; Honda, Kenya; Bry, Lynn; Gerber, Georg K

    2016-01-01

    Predicting dynamics of host-microbial ecosystems is crucial for the rational design of bacteriotherapies. We present MDSINE, a suite of algorithms for inferring dynamical systems models from microbiome time-series data and predicting temporal behaviors. Using simulated data, we demonstrate that MDSINE significantly outperforms the existing inference method. We then show MDSINE's utility on two new gnotobiotic mice datasets, investigating infection with Clostridium difficile and an immune-modulatory probiotic. Using these datasets, we demonstrate new capabilities, including accurate forecasting of microbial dynamics, prediction of stable sub-communities that inhibit pathogen growth, and identification of bacteria most crucial to community integrity in response to perturbations. PMID:27259475

  4. Complexity analyses show two distinct types of nonlinear dynamics in short heart period variability recordings

    PubMed Central

    Porta, Alberto; Bari, Vlasta; Marchi, Andrea; De Maria, Beatrice; Cysarz, Dirk; Van Leeuwen, Peter; Takahashi, Anielle C. M.; Catai, Aparecida M.; Gnecchi-Ruscone, Tomaso

    2015-01-01

    Two diverse complexity metrics quantifying time irreversibility and local prediction, in connection with a surrogate data approach, were utilized to detect nonlinear dynamics in short heart period (HP) variability series recorded in fetuses, as a function of the gestational period, and in healthy humans, as a function of the magnitude of the orthostatic challenge. The metrics indicated the presence of two distinct types of nonlinear HP dynamics characterized by diverse ranges of time scales. These findings stress the need to render more specific the analysis of nonlinear components of HP dynamics by accounting for different temporal scales. PMID:25806002

  5. Aeroelastic and dynamic finite element analyses of a bladder shrouded disk

    NASA Technical Reports Server (NTRS)

    Smith, G. C. C.; Elchuri, V.

    1980-01-01

    The delivery and demonstration of a computer program for the analysis of aeroelastic and dynamic properties is reported. Approaches to flutter and forced vibration of mistuned discs, and transient aerothermoelasticity are described.

  6. Digital processing of pulse signal from light-to-frequency converter under dynamic condition

    NASA Astrophysics Data System (ADS)

    Pawlowski, Eligiusz

    2014-08-01

    Frequency of an output signal from a Light-to-Frequency Converter (LFC) is proportional to light intensity. Under dynamic conditions, instantaneous frequency values represent instantaneous values of light intensity. In order to precisely determine frequency of the pulse signal in short time it is required to measure its successive periods. But if the light intensity changes, time between successive pulses of the output signal from LFC changes too, which prevents from obtaining the results of light measurement at regular time intervals. This work presents an algorithm for digital processing of a pulse frequency signal from LFC to obtain instantaneous values of light intensity at regular time intervals. Appropriate analytical dependences and examples of measurement results are also presented. Measurement circuit was built using DAQ-Card PCI-6602 and LabVIEW package of National Instruments.

  7. A novel computer simulation method for simulating the multiscale transduction dynamics of signal proteins

    NASA Astrophysics Data System (ADS)

    Peter, Emanuel; Dick, Bernhard; Baeurle, Stephan A.

    2012-03-01

    Signal proteins are able to adapt their response to a change in the environment, governing in this way a broad variety of important cellular processes in living systems. While conventional molecular-dynamics (MD) techniques can be used to explore the early signaling pathway of these protein systems at atomistic resolution, the high computational costs limit their usefulness for the elucidation of the multiscale transduction dynamics of most signaling processes, occurring on experimental timescales. To cope with the problem, we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1), recently employed to control the motility of cancer cells through light stimulus. More specifically, we show that their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain. In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding. These applications demonstrate that our approach reliably reproduces the signaling pathways of complex signal proteins, ranging from nanoseconds up to seconds at affordable computational costs.

  8. A novel computer simulation method for simulating the multiscale transduction dynamics of signal proteins.

    PubMed

    Peter, Emanuel; Dick, Bernhard; Baeurle, Stephan A

    2012-03-28

    Signal proteins are able to adapt their response to a change in the environment, governing in this way a broad variety of important cellular processes in living systems. While conventional molecular-dynamics (MD) techniques can be used to explore the early signaling pathway of these protein systems at atomistic resolution, the high computational costs limit their usefulness for the elucidation of the multiscale transduction dynamics of most signaling processes, occurring on experimental timescales. To cope with the problem, we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1), recently employed to control the motility of cancer cells through light stimulus. More specifically, we show that their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain. In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding. These applications demonstrate that our approach reliably reproduces the signaling pathways of complex signal proteins, ranging from nanoseconds up to seconds at affordable computational costs. PMID:22462840

  9. Analyses of evolutionary dynamics in viruses are hindered by a time-dependent bias in rate estimates

    PubMed Central

    Duchêne, Sebastián; Holmes, Edward C.; Ho, Simon Y. W.

    2014-01-01

    Time-scales of viral evolution and emergence have been studied widely, but are often poorly understood. Molecular analyses of viral evolutionary time-scales generally rely on estimates of rates of nucleotide substitution, which vary by several orders of magnitude depending on the timeframe of measurement. We analysed data from all major groups of viruses and found a strong negative relationship between estimates of nucleotide substitution rate and evolutionary timescale. Strikingly, this relationship was upheld both within and among diverse groups of viruses. A detailed case study of primate lentiviruses revealed that the combined effects of sequence saturation and purifying selection can explain this time-dependent pattern of rate variation. Therefore, our analyses show that studies of evolutionary time-scales in viruses require a reconsideration of substitution rates as a dynamic, rather than as a static, feature of molecular evolution. Improved modelling of viral evolutionary rates has the potential to change our understanding of virus origins. PMID:24850916

  10. Integration of sensitivity and bifurcation analysis to detect critical processes in a model combining signalling and cell population dynamics

    NASA Astrophysics Data System (ADS)

    Nikolov, S.; Lai, X.; Liebal, U. W.; Wolkenhauer, O.; Vera, J.

    2010-01-01

    In this article we present and test a strategy to integrate, in a sequential manner, sensitivity analysis, bifurcation analysis and predictive simulations. Our strategy uses some of these methods in a coordinated way such that information, generated in one step, feeds into the definition of further analyses and helps refining the structure of the mathematical model. The aim of the method is to help in the designing of more informative predictive simulations, which focus on critical model parameters and the biological effects of their modulation. We tested our methodology with a multilevel model, accounting for the effect of erythropoietin (Epo)-mediated JAK2-STAT5 signalling in erythropoiesis. Our analysis revealed that time-delays associated with the proliferation-differentiation process are critical to induce pathological sustained oscillations, whereas the modulation of time-delays related to intracellular signalling and hypoxia-controlled physiological dynamics is not enough to induce self-oscillations in the system. Furthermore, our results suggest that the system is able to compensate (through the physiological-level feedback loop on hypoxia) the partial impairment of intracellular signalling processes (downregulation or overexpression of Epo receptor complex and STAT5), but cannot control impairment in some critical physiological-level processes, which provoke the emergence of pathological oscillations.

  11. Gating based on internal/external signals with dynamic correlation updates

    NASA Astrophysics Data System (ADS)

    Wu, Huanmei; Zhao, Qingya; Berbeco, Ross I.; Nishioka, Seiko; Shirato, Hiroki; Jiang, Steve B.

    2008-12-01

    Precise localization of mobile tumor positions in real time is critical to the success of gated radiotherapy. Tumor positions are usually derived from either internal or external surrogates. Fluoroscopic gating based on internal surrogates, such as implanted fiducial markers, is accurate however requiring a large amount of imaging dose. Gating based on external surrogates, such as patient abdominal surface motion, is non-invasive however less accurate due to the uncertainty in the correlation between tumor location and external surrogates. To address these complications, we propose to investigate an approach based on hybrid gating with dynamic internal/external correlation updates. In this approach, the external signal is acquired at high frequency (such as 30 Hz) while the internal signal is sparsely acquired (such as 0.5 Hz or less). The internal signal is used to validate and update the internal/external correlation during treatment. Tumor positions are derived from the external signal based on the newly updated correlation. Two dynamic correlation updating algorithms are introduced. One is based on the motion amplitude and the other is based on the motion phase. Nine patients with synchronized internal/external motion signals are simulated retrospectively to evaluate the effectiveness of hybrid gating. The influences of different clinical conditions on hybrid gating, such as the size of gating windows, the optimal timing for internal signal acquisition and the acquisition frequency are investigated. The results demonstrate that dynamically updating the internal/external correlation in or around the gating window will reduce false positive with relatively diminished treatment efficiency. This improvement will benefit patients with mobile tumors, especially greater for early stage lung cancers, for which the tumors are less attached or freely floating in the lung.

  12. Ongoing Analyses of Rocket Based Combined Cycle Engines by the Applied Fluid Dynamics Analysis Group at Marshall Space Flight Center

    NASA Technical Reports Server (NTRS)

    Ruf, Joseph H.; Holt, James B.; Canabal, Francisco

    2001-01-01

    This paper presents the status of analyses on three Rocket Based Combined Cycle (RBCC) configurations underway in the Applied Fluid Dynamics Analysis Group (TD64). TD64 is performing computational fluid dynamics (CFD) analysis on a Penn State RBCC test rig, the proposed Draco axisymmetric RBCC engine and the Trailblazer engine. The intent of the analysis on the Penn State test rig is to benchmark the Finite Difference Navier Stokes (FDNS) code for ejector mode fluid dynamics. The Draco analysis was a trade study to determine the ejector mode performance as a function of three engine design variables. The Trailblazer analysis is to evaluate the nozzle performance in scramjet mode. Results to date of each analysis are presented.

  13. Single-Cell Gene Expression Analyses Reveal Heterogeneous Responsiveness of Fetal Innate Lymphoid Progenitors to Notch Signaling.

    PubMed

    Chea, Sylvestre; Schmutz, Sandrine; Berthault, Claire; Perchet, Thibaut; Petit, Maxime; Burlen-Defranoux, Odile; Goldrath, Ananda W; Rodewald, Hans-Reimer; Cumano, Ana; Golub, Rachel

    2016-02-16

    T and innate lymphoid cells (ILCs) share some aspects of their developmental programs. However, although Notch signaling is strictly required for T cell development, it is dispensable for fetal ILC development. Constitutive activation of Notch signaling, at the common lymphoid progenitor stage, drives T cell development and abrogates ILC development by preventing Id2 expression. By combining single-cell transcriptomics and clonal culture strategies, we characterize two heterogeneous α4β7-expressing lymphoid progenitor compartments. αLP1 (Flt3(+)) still retains T cell potential and comprises the global ILC progenitor, while αLP2 (Flt3(-)) consists of ILC precursors that are primed toward the different ILC lineages. Only a subset of αLP2 precursors is sensitive to Notch signaling required for their proliferation. Our study identifies, in a refined manner, the diversity of transitional stages of ILC development, their transcriptional signatures, and their differential dependence on Notch signaling. PMID:26832410

  14. Correlation of ground tests and analyses of a dynamically scaled space station model configuration

    NASA Technical Reports Server (NTRS)

    Javeed, Mehzad; Edighoffer, Harold H.; Mcgowan, Paul E.

    1993-01-01

    Verification of analytical models through correlation with ground test results of a complex space truss structure is demonstrated. A multi-component, dynamically scaled space station model configuration is the focus structure for this work. Previously established test/analysis correlation procedures are used to develop improved component analytical models. Integrated system analytical models, consisting of updated component analytical models, are compared with modal test results to establish the accuracy of system-level dynamic predictions. Design sensitivity model updating methods are shown to be effective for providing improved component analytical models. Also, the effects of component model accuracy and interface modeling fidelity on the accuracy of integrated model predictions is examined.

  15. Correlation of ground tests and analyses of a dynamically scaled Space Station model configuration

    NASA Technical Reports Server (NTRS)

    Javeed, Mehzad; Edighoffer, Harold H.; Mcgowan, Paul E.

    1993-01-01

    Verification of analytical models through correlation with ground test results of a complex space truss structure is demonstrated. A multi-component, dynamically scaled space station model configuration is the focus structure for this work. Previously established test/analysis correlation procedures are used to develop improved component analytical models. Integrated system analytical models, consisting of updated component analytical models, are compared with modal test results to establish the accuracy of system-level dynamic predictions. Design sensitivity model updating methods are shown to be effective for providing improved component analytical models. Also, the effects of component model accuracy and interface modeling fidelity on the accuracy of integrated model predictions is examined.

  16. Abstract and Effector-Selective Decision Signals Exhibit Qualitatively Distinct Dynamics before Delayed Perceptual Reports

    PubMed Central

    Twomey, Deirdre M.; Kelly, Simon P.

    2016-01-01

    Electrophysiological research has isolated neural signatures of decision formation in a variety of brain regions. Studies in rodents and monkeys have focused primarily on effector-selective signals that translate the emerging decision into a specific motor plan, but, more recently, research on the human brain has identified an abstract signature of evidence accumulation that does not appear to play any direct role in action preparation. The functional dissociations between these distinct signal types have only begun to be characterized, and their dynamics during decisions with deferred actions with or without foreknowledge of stimulus-effector mapping, a commonly studied task scenario in single-unit and functional imaging investigations, have not been established. Here we traced the dynamics of distinct abstract and effector-selective decision signals in the form of the broad-band centro-parietal positivity (CPP) and limb-selective β-band (8–16 and 18–30 Hz) EEG activity, respectively, during delayed-reported motion direction decisions with and without foreknowledge of direction-response mapping. With foreknowledge, the CPP and β-band signals exhibited a similar gradual build-up following evidence onset, but whereas choice-predictive β-band activity persisted up until the delayed response, the CPP dropped toward baseline after peaking. Without foreknowledge, the CPP exhibited identical dynamics, whereas choice-selective β-band activity was eliminated. These findings highlight qualitative functional distinctions between effector-selective and abstract decision signals and are of relevance to the assumptions founding functional neuroimaging investigations of decision-making. SIGNIFICANCE STATEMENT Neural signatures of evidence accumulation have been isolated in numerous brain regions. Although animal neurophysiology has largely concentrated on effector-selective decision signals that translate the emerging decision into a specific motor plan, recent research

  17. The Evolution and Origin of Animal Toll-Like Receptor Signaling Pathway Revealed by Network-Level Molecular Evolutionary Analyses

    PubMed Central

    Qin, Sheng; Chen, Liming; Ma, Fei

    2012-01-01

    Genes carry out their biological functions through pathways in complex networks consisting of many interacting molecules. Studies on the effect of network architecture on the evolution of individual proteins will provide valuable information for understanding the origin and evolution as well as functional conservation of signaling pathways. However, the relationship between the network architecture and the individual protein sequence evolution is yet little known. In current study, we carried out network-level molecular evolution analysis on TLR (Toll-like receptor ) signaling pathway, which plays an important role in innate immunity in insects and mammals, and we found that: 1) The selection constraint of genes was negatively correlated with its position along TLR signaling pathway; 2) all genes in TLR signaling pathway were highly conserved and underwent strong purifying selection; 3) the distribution of selective pressure along the pathway was driven by differential nonsynonymous substitution levels; 4) The TLR signaling pathway might present in a common ancestor of sponges and eumetazoa, and evolve via the TLR, IKK, IκB and NF-κB genes underwent duplication events as well as adaptor molecular enlargement, and gene structure and conservation motif of NF-κB genes shifted in their evolutionary history. Our results will improve our understanding on the evolutionary history of animal TLR signaling pathway as well as the relationship between the network architecture and the sequences evolution of individual protein. PMID:23236523

  18. Spatial analyses of soil properties, terrain, and water dynamics in a semi-arid agricultural landscape

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Quantification of soil-water patterns in space and time is essential for understanding soil hydrological processes and to aid land management decisions. In undulating terrain, dynamics of profile soil water can vary by landscape position in relation to terrain attributes, soil properties, and plant ...

  19. Three-dimensional imaging system for analyses of dynamic droplet impaction and deposition formation on leaves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A system was developed to assess the dynamic processes of droplet impact, rebound and retention on leaf surfaces with three-dimensional (3-D) images. The system components consisted of a uniform-size droplet generator, two high speed digital video cameras, a constant speed track, a leaf holder, and ...

  20. Adaptive coded spreading OFDM signal for dynamic-λ optical access network

    NASA Astrophysics Data System (ADS)

    Liu, Bo; Zhang, Lijia; Xin, Xiangjun

    2015-12-01

    This paper proposes and experimentally demonstrates a novel adaptive coded spreading (ACS) orthogonal frequency division multiplexing (OFDM) signal for dynamic distributed optical ring-based access network. The wavelength can be assigned to different remote nodes (RNs) according to the traffic demand of optical network unit (ONU). The ACS can provide dynamic spreading gain to different signals according to the split ratio or transmission length, which offers flexible power budget for the network. A 10×13.12 Gb/s OFDM access with ACS is successfully demonstrated over two RNs and 120 km transmission in the experiment. The demonstrated method may be viewed as one promising for future optical metro access network.

  1. Spacecraft attitude control systems with dynamic methods and structures for processing star tracker signals

    NASA Technical Reports Server (NTRS)

    Liu, Yong (Inventor); Wu, Yeong-Wei Andy (Inventor); Li, Rongsheng (Inventor)

    2001-01-01

    Methods are provided for dynamically processing successively-generated star tracker data frames and associated valid flags to generate processed star tracker signals that have reduced noise and a probability greater than a selected probability P.sub.slctd of being valid. These methods maintain accurate spacecraft attitude control in the presence of spurious inputs (e.g., impinging protons) that corrupt collected charges in spacecraft star trackers. The methods of the invention enhance the probability of generating valid star tracker signals because they respond to a current frame probability P.sub.frm by dynamically selecting the largest valid frame combination whose combination probability P.sub.cmb satisfies a selected probability P.sub.slctd. Noise is thus reduced while the probability of finding a valid frame combination is enhanced. Spacecraft structures are also provided for practicing the methods of the invention.

  2. Self-organization of traffic jams in cities: Effects of stochastic dynamics and signal periods

    NASA Astrophysics Data System (ADS)

    Chowdhury, Debashish; Schadschneider, Andreas

    1999-02-01

    We propose a cellular automata model for vehicular traffic in cities by combining (and appropriately modifying) ideas borrowed from the Biham-Middleton-Levine (BML) model of city traffic and the Nagel-Schreckenberg (NS) model of highway traffic. We demonstrate a phase transition from the ``free-flowing'' dynamical phase to the completely ``jammed'' phase at a vehicle density which depends on the time periods of the synchronized signals and the separation between them. The intrinsic stochasticity of the dynamics, which triggers the onset of jamming, is similar to that in the NS model, while the phenomenon of complete jamming through self-organization as well as the final jammed configurations are similar to those in the BML model. Using our model, we have made an investigation of the time dependence of the average speeds of the cars in the ``free-flowing'' phase as well as the dependence of flux and jamming on the time period of the signals.

  3. Multiplexed visualization of dynamic signaling networks using genetically encoded fluorescent protein-based biosensors

    PubMed Central

    Depry, Charlene; Mehta, Sohum; Zhang, Jin

    2012-01-01

    Cells rely on a complex, interconnected network of signaling pathways to sense and interpret changes in their extracellular environment. The development of genetically encoded fluorescent protein (FP)-based biosensors has made it possible for researchers to directly observe and characterize the spatiotemporal dynamics of these intracellular signaling pathways in living cells. However, detailed information regarding the precise temporal and spatial relationships between intersecting pathways is often lost when individual signaling events are monitored in isolation. As the development of biosensor technology continues to advance, it is becoming increasingly feasible to image multiple FP-based biosensors concurrently, permitting greater insights into the intricate coordination of intracellular signaling networks by enabling parallel monitoring of distinct signaling events within the same cell. In this review, we discuss several strategies for multiplexed imaging of FP-based biosensors, while also underscoring some of the challenges associated with these techniques and highlighting additional avenues that could lead to further improvements in parallel monitoring of intracellular signaling events. PMID:23138230

  4. Dynamic characteristics of laser Doppler flowmetry signals obtained in response to a local and progressive pressure applied on diabetic and healthy subjects

    NASA Astrophysics Data System (ADS)

    Humeau, Anne; Koitka, Audrey; Abraham, Pierre; Saumet, Jean-Louis; L'Huillier, Jean-Pierre

    2004-09-01

    In the biomedical field, the laser Doppler flowmetry (LDF) technique is a non-invasive method to monitor skin perfusion. On the skin of healthy humans, LDF signals present a significant transient increase in response to a local and progressive pressure application. This vasodilatory reflex response may have important implications for cutaneous pathologies involved in various neurological diseases and in the pathophysiology of decubitus ulcers. The present work analyses the dynamic characteristics of these signals on young type 1 diabetic patients, and on healthy age-matched subjects. To obtain accurate dynamic characteristic values, a de-noising wavelet-based algorithm is first applied to LDF signals. All the de-noised signals are then normalised to the same value. The blood flow peak and the time to reach this peak are then calculated on each computed signal. The results show that a large vasodilation is present on signals of healthy subjects. The mean peak occurs at a pressure of 3.2 kPa approximately. However, a vasodilation of limited amplitude appears on type 1 diabetic patients. The maximum value is visualised, on the average, when the pressure is 1.1 kPa. The inability for diabetic patients to increase largely their cutaneous blood flow may bring explanations to foot ulcers.

  5. Dynamic changes in brewing yeast cells in culture revealed by statistical analyses of yeast morphological data.

    PubMed

    Ohnuki, Shinsuke; Enomoto, Kenichi; Yoshimoto, Hiroyuki; Ohya, Yoshikazu

    2014-03-01

    The vitality of brewing yeasts has been used to monitor their physiological state during fermentation. To investigate the fermentation process, we used the image processing software, CalMorph, which generates morphological data on yeast mother cells and bud shape, nuclear shape and location, and actin distribution. We found that 248 parameters changed significantly during fermentation. Successive use of principal component analysis (PCA) revealed several important features of yeast, providing insight into the dynamic changes in the yeast population. First, PCA indicated that much of the observed variability in the experiment was summarized in just two components: a change with a peak and a change over time. Second, PCA indicated the independent and important morphological features responsible for dynamic changes: budding ratio, nucleus position, neck position, and actin organization. Thus, the large amount of data provided by imaging analysis can be used to monitor the fermentation processes involved in beer and bioethanol production. PMID:24012106

  6. Kinematic and dynamic analyses of the Stanford/JPL robot hand. [MACSYMA

    SciTech Connect

    Johnson, V.J.; Starr, G.P.

    1987-11-01

    This report develops the kinematic and dynamic equations for one finger of the three-fingered Stanford/JPL robot hand and documents the physical parameters needed to implement the equations. The equations can be used in control schemes for position and force control of the Stanford/JPL robot hand. The output file for the MACSYMA program is given. 4 refs., 6 figs., 1 tab.

  7. Quantitative Signaling and Structure-Activity Analyses Demonstrate Functional Selectivity at the Nociceptin/Orphanin FQ Opioid Receptor.

    PubMed

    Chang, Steven D; Mascarella, S Wayne; Spangler, Skylar M; Gurevich, Vsevolod V; Navarro, Hernan A; Carroll, F Ivy; Bruchas, Michael R

    2015-09-01

    Comprehensive studies that consolidate selective ligands, quantitative comparisons of G protein versus arrestin-2/3 coupling, together with structure-activity relationship models for G protein-coupled receptor (GPCR) systems are less commonly employed. Here we examine biased signaling at the nociceptin/orphanin FQ opioid receptor (NOPR), the most recently identified member of the opioid receptor family. Using real-time, live-cell assays, we identified the signaling profiles of several NOPR-selective ligands in upstream GPCR signaling (G protein and arrestin pathways) to determine their relative transduction coefficients and signaling bias. Complementing this analysis, we designed novel ligands on the basis of NOPR antagonist J-113,397 [(±)-1-[(3R*,4R*)-1-(cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one] to explore structure-activity relationships. Our study shows that NOPR is capable of biased signaling, and further, the NOPR selective ligands MCOPPB [1-[1-(1-methylcyclooctyl)-4-piperidinyl]-2-(3R)-3-piperidinyl-1H-benzimidazole trihydrochloride] and NNC 63-0532 [8-(1-naphthalenylmethyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-3-acetic acid, methyl ester] are G protein-biased agonists. Additionally, minor structural modification of J-113,397 can dramatically shift signaling from antagonist to partial agonist activity. We explore these findings with in silico modeling of binding poses. This work is the first to demonstrate functional selectivity and identification of biased ligands at the nociceptin opioid receptor. PMID:26134494

  8. Communication: Dynamical and structural analyses of solid hydrogen under vapor pressure

    SciTech Connect

    Hyeon-Deuk, Kim; Ando, Koji

    2015-11-07

    Nuclear quantum effects play a dominant role in determining the phase diagram of H{sub 2}. With a recently developed quantum molecular dynamics simulation method, we examine dynamical and structural characters of solid H{sub 2} under vapor pressure, demonstrating the difference from liquid and high-pressure solid H{sub 2}. While stable hexagonal close-packed lattice structures are reproduced with reasonable lattice phonon frequencies, the most stable adjacent configuration exhibits a zigzag structure, in contrast with the T-shape liquid configuration. The periodic angular distributions of H{sub 2} molecules indicate that molecules are not a completely free rotor in the vapor-pressure solid reflecting asymmetric potentials from surrounding molecules on adjacent lattice sites. Discrete jumps of librational and H–H vibrational frequencies as well as H–H bond length caused by structural rearrangements under vapor pressure effectively discriminate the liquid and solid phases. The obtained dynamical and structural information of the vapor-pressure H{sub 2} solid will be useful in monitoring thermodynamic states of condensed hydrogens.

  9. Feasible muscle activation ranges based on inverse dynamics analyses of human walking.

    PubMed

    Simpson, Cole S; Sohn, M Hongchul; Allen, Jessica L; Ting, Lena H

    2015-09-18

    Although it is possible to produce the same movement using an infinite number of different muscle activation patterns owing to musculoskeletal redundancy, the degree to which observed variations in muscle activity can deviate from optimal solutions computed from biomechanical models is not known. Here, we examined the range of biomechanically permitted activation levels in individual muscles during human walking using a detailed musculoskeletal model and experimentally-measured kinetics and kinematics. Feasible muscle activation ranges define the minimum and maximum possible level of each muscle's activation that satisfy inverse dynamics joint torques assuming that all other muscles can vary their activation as needed. During walking, 73% of the muscles had feasible muscle activation ranges that were greater than 95% of the total muscle activation range over more than 95% of the gait cycle, indicating that, individually, most muscles could be fully active or fully inactive while still satisfying inverse dynamics joint torques. Moreover, the shapes of the feasible muscle activation ranges did not resemble previously-reported muscle activation patterns nor optimal solutions, i.e. static optimization and computed muscle control, that are based on the same biomechanical constraints. Our results demonstrate that joint torque requirements from standard inverse dynamics calculations are insufficient to define the activation of individual muscles during walking in healthy individuals. Identifying feasible muscle activation ranges may be an effective way to evaluate the impact of additional biomechanical and/or neural constraints on possible versus actual muscle activity in both normal and impaired movements. PMID:26300401

  10. Using temperature to analyse temporal dynamics in the songbird motor pathway.

    PubMed

    Long, Michael A; Fee, Michale S

    2008-11-13

    Many complex behaviours, like speech or music, have a hierarchical organization with structure on many timescales, but it is not known how the brain controls the timing of behavioural sequences, or whether different circuits control different timescales of the behaviour. Here we address these issues by using temperature to manipulate the biophysical dynamics in different regions of the songbird forebrain involved in song production. We find that cooling the premotor nucleus HVC (formerly known as the high vocal centre) slows song speed across all timescales by up to 45 per cent but only slightly alters the acoustic structure, whereas cooling the downstream motor nucleus RA (robust nucleus of the arcopallium) has no observable effect on song timing. Our observations suggest that dynamics within HVC are involved in the control of song timing, perhaps through a chain-like organization. Local manipulation of brain temperature should be broadly applicable to the identification of neural circuitry that controls the timing of behavioural sequences and, more generally, to the study of the origin and role of oscillatory and other forms of brain dynamics in neural systems. PMID:19005546

  11. A multi-scale modelling approach for analysing landscape service dynamics.

    PubMed

    Willemen, L; Veldkamp, A; Verburg, P H; Hein, L; Leemans, R

    2012-06-15

    Shifting societal needs drive and shape landscapes and the provision of their services. This paper presents a modelling approach to visualize the regional spatial and temporal dynamics in landscape service supply as a function of changing landscapes and societal demand. This changing demand can result from different policy targets. In this paper we conceptualise the system in which these dynamics take place by explicitly addressing (i) the multifunctional character of a landscape, (ii) the different spatial levels at which interactions between landscape service supply, demand, and land management occur, and (iii) trade-offs in service supply as a result of land management actions. Next, we translate the resulting conceptual framework into an operational model. As a demonstration, this model is applied to simulate changes in landscape service supply driven by regional policies in a rural region of the Netherlands. This application demonstrates potential trade-offs, which emerge in a spatially explicit way in the region over time. It illustrates the potential relevance of modelling landscape service dynamics for environmental management and decision making. PMID:22366361

  12. Assessing dynamics, spatial scale, and uncertainty in task-related brain network analyses.

    PubMed

    Stephen, Emily P; Lepage, Kyle Q; Eden, Uri T; Brunner, Peter; Schalk, Gerwin; Brumberg, Jonathan S; Guenther, Frank H; Kramer, Mark A

    2014-01-01

    The brain is a complex network of interconnected elements, whose interactions evolve dynamically in time to cooperatively perform specific functions. A common technique to probe these interactions involves multi-sensor recordings of brain activity during a repeated task. Many techniques exist to characterize the resulting task-related activity, including establishing functional networks, which represent the statistical associations between brain areas. Although functional network inference is commonly employed to analyze neural time series data, techniques to assess the uncertainty-both in the functional network edges and the corresponding aggregate measures of network topology-are lacking. To address this, we describe a statistically principled approach for computing uncertainty in functional networks and aggregate network measures in task-related data. The approach is based on a resampling procedure that utilizes the trial structure common in experimental recordings. We show in simulations that this approach successfully identifies functional networks and associated measures of confidence emergent during a task in a variety of scenarios, including dynamically evolving networks. In addition, we describe a principled technique for establishing functional networks based on predetermined regions of interest using canonical correlation. Doing so provides additional robustness to the functional network inference. Finally, we illustrate the use of these methods on example invasive brain voltage recordings collected during an overt speech task. The general strategy described here-appropriate for static and dynamic network inference and different statistical measures of coupling-permits the evaluation of confidence in network measures in a variety of settings common to neuroscience. PMID:24678295

  13. Assessing dynamics, spatial scale, and uncertainty in task-related brain network analyses

    PubMed Central

    Stephen, Emily P.; Lepage, Kyle Q.; Eden, Uri T.; Brunner, Peter; Schalk, Gerwin; Brumberg, Jonathan S.; Guenther, Frank H.; Kramer, Mark A.

    2014-01-01

    The brain is a complex network of interconnected elements, whose interactions evolve dynamically in time to cooperatively perform specific functions. A common technique to probe these interactions involves multi-sensor recordings of brain activity during a repeated task. Many techniques exist to characterize the resulting task-related activity, including establishing functional networks, which represent the statistical associations between brain areas. Although functional network inference is commonly employed to analyze neural time series data, techniques to assess the uncertainty—both in the functional network edges and the corresponding aggregate measures of network topology—are lacking. To address this, we describe a statistically principled approach for computing uncertainty in functional networks and aggregate network measures in task-related data. The approach is based on a resampling procedure that utilizes the trial structure common in experimental recordings. We show in simulations that this approach successfully identifies functional networks and associated measures of confidence emergent during a task in a variety of scenarios, including dynamically evolving networks. In addition, we describe a principled technique for establishing functional networks based on predetermined regions of interest using canonical correlation. Doing so provides additional robustness to the functional network inference. Finally, we illustrate the use of these methods on example invasive brain voltage recordings collected during an overt speech task. The general strategy described here—appropriate for static and dynamic network inference and different statistical measures of coupling—permits the evaluation of confidence in network measures in a variety of settings common to neuroscience. PMID:24678295

  14. Communication: Dynamical and structural analyses of solid hydrogen under vapor pressure

    NASA Astrophysics Data System (ADS)

    Hyeon-Deuk, Kim; Ando, Koji

    2015-11-01

    Nuclear quantum effects play a dominant role in determining the phase diagram of H2. With a recently developed quantum molecular dynamics simulation method, we examine dynamical and structural characters of solid H2 under vapor pressure, demonstrating the difference from liquid and high-pressure solid H2. While stable hexagonal close-packed lattice structures are reproduced with reasonable lattice phonon frequencies, the most stable adjacent configuration exhibits a zigzag structure, in contrast with the T-shape liquid configuration. The periodic angular distributions of H2 molecules indicate that molecules are not a completely free rotor in the vapor-pressure solid reflecting asymmetric potentials from surrounding molecules on adjacent lattice sites. Discrete jumps of librational and H-H vibrational frequencies as well as H-H bond length caused by structural rearrangements under vapor pressure effectively discriminate the liquid and solid phases. The obtained dynamical and structural information of the vapor-pressure H2 solid will be useful in monitoring thermodynamic states of condensed hydrogens.

  15. Communication: Dynamical and structural analyses of solid hydrogen under vapor pressure.

    PubMed

    Hyeon-Deuk, Kim; Ando, Koji

    2015-11-01

    Nuclear quantum effects play a dominant role in determining the phase diagram of H2. With a recently developed quantum molecular dynamics simulation method, we examine dynamical and structural characters of solid H2 under vapor pressure, demonstrating the difference from liquid and high-pressure solid H2. While stable hexagonal close-packed lattice structures are reproduced with reasonable lattice phonon frequencies, the most stable adjacent configuration exhibits a zigzag structure, in contrast with the T-shape liquid configuration. The periodic angular distributions of H2 molecules indicate that molecules are not a completely free rotor in the vapor-pressure solid reflecting asymmetric potentials from surrounding molecules on adjacent lattice sites. Discrete jumps of librational and H-H vibrational frequencies as well as H-H bond length caused by structural rearrangements under vapor pressure effectively discriminate the liquid and solid phases. The obtained dynamical and structural information of the vapor-pressure H2 solid will be useful in monitoring thermodynamic states of condensed hydrogens. PMID:26547150

  16. Topology and dynamics of signaling networks: in search of transcriptional control of the inflammatory response.

    PubMed

    Androulakis, Ioannis P; Kamisoglu, Kubra; Mattick, John S

    2013-01-01

    Over the past several decades, to develop a fundamental understanding of inflammation's progression, research has focused on extracellular mediators, such as cytokines, as characteristic components of inflammatory response. These efforts have recently been complemented by advances in proteomics that allow analysis of multiple signaling proteins in parallel, to provide more complete mechanistic models of inflammation. In this review, we discuss various techniques for assessing protein activity, as well as computational techniques that are well suited for interpreting large amounts of proteomic data to generate signaling networks or for modeling the dynamics of known network interactions. We also discuss examples that explore these experimental and computational techniques in tandem to generate signaling networks under various conditions and that link those networks to transcriptional activity. Further advancements in this field will likely provide an explicit description of inflammatory response, paving the way for better diagnostics and therapies in clinic. PMID:23862674

  17. Weak and Dynamic GNSS Signal Tracking Strategies for Flight Missions in the Space Service Volume.

    PubMed

    Jing, Shuai; Zhan, Xingqun; Liu, Baoyu; Chen, Maolin

    2016-01-01

    Weak-signal and high-dynamics are of two primary concerns of space navigation using GNSS (Global Navigation Satellite System) in the space service volume (SSV). The paper firstly defines a reference assumption third-order phase-locked loop (PLL) as the baseline of an onboard GNSS receiver, and proves the incompetence of this conventional architecture. Then an adaptive four-state Kalman filter (KF)-based algorithm is introduced to realize the optimization of loop noise bandwidth, which can adaptively regulate its filter gain according to the received signal power and line-of-sight (LOS) dynamics. To overcome the matter of losing lock in weak-signal and high-dynamic environments, an open loop tracking strategy aided by an inertial navigation system (INS) is recommended, and the traditional maximum likelihood estimation (MLE) method is modified in a non-coherent way by reconstructing the likelihood cost function. Furthermore, a typical mission with combined orbital maneuvering and non-maneuvering arcs is taken as a destination object to test the two proposed strategies. Finally, the experiment based on computer simulation identifies the effectiveness of an adaptive four-state KF-based strategy under non-maneuvering conditions and the virtue of INS-assisted methods under maneuvering conditions. PMID:27598164

  18. Digital-signal-processor-based dynamic imaging system for optical tomography.

    PubMed

    Lasker, Joseph M; Masciotti, James M; Schoenecker, Matthew; Schmitz, Christoph H; Hielscher, Andreas H

    2007-08-01

    In this article, we introduce a dynamic optical tomography system that is, unlike currently available analog instrumentation, based on digital data acquisition and filtering techniques. At the core of this continuous wave instrument is a digital signal processor (DSP) that collects, collates, processes, and filters the digitized data set. The processor is also responsible for managing system timing and the imaging routines which can acquire real-time data at rates as high as 150 Hz. Many of the synchronously timed processes are controlled by a complex programmable logic device that is also used in conjunction with the DSP to orchestrate data flow. The operation of the system is implemented through a comprehensive graphical user interface designed with LABVIEW software which integrates automated calibration, data acquisition, data organization, and signal postprocessing. Performance analysis demonstrates very low system noise (approximately 1 pW rms noise equivalent power), excellent signal precision (<0.04%-0.2%) and long term system stability (<1% over 40 min). A large dynamic range (approximately 190 dB) accommodates a wide scope of measurement geometries and tissue types. First experiments on tissue phantoms show that dynamic behavior is accurately captured and spatial location can be correctly tracked using this system. PMID:17764328

  19. Identifying early-warning signals of critical transitions with strong noise by dynamical network markers

    PubMed Central

    Liu, Rui; Chen, Pei; Aihara, Kazuyuki; Chen, Luonan

    2015-01-01

    Identifying early-warning signals of a critical transition for a complex system is difficult, especially when the target system is constantly perturbed by big noise, which makes the traditional methods fail due to the strong fluctuations of the observed data. In this work, we show that the critical transition is not traditional state-transition but probability distribution-transition when the noise is not sufficiently small, which, however, is a ubiquitous case in real systems. We present a model-free computational method to detect the warning signals before such transitions. The key idea behind is a strategy: “making big noise smaller” by a distribution-embedding scheme, which transforms the data from the observed state-variables with big noise to their distribution-variables with small noise, and thus makes the traditional criteria effective because of the significantly reduced fluctuations. Specifically, increasing the dimension of the observed data by moment expansion that changes the system from state-dynamics to probability distribution-dynamics, we derive new data in a higher-dimensional space but with much smaller noise. Then, we develop a criterion based on the dynamical network marker (DNM) to signal the impending critical transition using the transformed higher-dimensional data. We also demonstrate the effectiveness of our method in biological, ecological and financial systems. PMID:26647650

  20. High-throughput microfluidics to control and measure signaling dynamics in single yeast cells

    PubMed Central

    Hansen, Anders S.; Hao, Nan; O'Shea, Erin K.

    2015-01-01

    Microfluidics coupled to quantitative time-lapse fluorescence microscopy is transforming our ability to control, measure, and understand signaling dynamics in single living cells. Here we describe a pipeline that incorporates multiplexed microfluidic cell culture, automated programmable fluid handling for cell perturbation, quantitative time-lapse microscopy, and computational analysis of time-lapse movies. We illustrate how this setup can be used to control the nuclear localization of the budding yeast transcription factor Msn2. Using this protocol, we generate oscillations of Msn2 localization and measure the dynamic gene expression response of individual genes in single cells. The protocol allows a single researcher to perform up to 20 different experiments in a single day, whilst collecting data for thousands of single cells. Compared to other protocols, the present protocol is relatively easy to adopt and higher-throughput. The protocol can be widely used to control and monitor single-cell signaling dynamics in other signal transduction systems in microorganisms. PMID:26158443

  1. Cellular context–mediated Akt dynamics regulates MAP kinase signaling thresholds during angiogenesis

    PubMed Central

    Hellesøy, Monica; Lorens, James B.

    2015-01-01

    The formation of new blood vessels by sprouting angiogenesis is tightly regulated by contextual cues that affect angiogeneic growth factor signaling. Both constitutive activation and loss of Akt kinase activity in endothelial cells impair angiogenesis, suggesting that Akt dynamics mediates contextual microenvironmental regulation. We explored the temporal regulation of Akt in endothelial cells during formation of capillary-like networks induced by cell–cell contact with vascular smooth muscle cells (vSMCs) and vSMC-associated VEGF. Expression of constitutively active Akt1 strongly inhibited network formation, whereas hemiphosphorylated Akt1 epi-alleles with reduced kinase activity had an intermediate inhibitory effect. Conversely, inhibition of Akt signaling did not affect endothelial cell migration or morphogenesis in vSMC cocultures that generate capillary-like structures. We found that endothelial Akt activity is transiently blocked by proteasomal degradation in the presence of SMCs during the initial phase of capillary-like structure formation. Suppressed Akt activity corresponded to the increased endothelial MAP kinase signaling that was required for angiogenic endothelial morphogenesis. These results reveal a regulatory principle by which cellular context regulates Akt protein dynamics, which determines MAP kinase signaling thresholds necessary drive a morphogenetic program during angiogenesis. PMID:26023089

  2. Detection of allosteric signal transmission by information-theoretic analysis of protein dynamics.

    PubMed

    Pandini, Alessandro; Fornili, Arianna; Fraternali, Franca; Kleinjung, Jens

    2012-02-01

    Allostery offers a highly specific way to modulate protein function. Therefore, understanding this mechanism is of increasing interest for protein science and drug discovery. However, allosteric signal transmission is difficult to detect experimentally and to model because it is often mediated by local structural changes propagating along multiple pathways. To address this, we developed a method to identify communication pathways by an information-theoretical analysis of molecular dynamics simulations. Signal propagation was described as information exchange through a network of correlated local motions, modeled as transitions between canonical states of protein fragments. The method was used to describe allostery in two-component regulatory systems. In particular, the transmission from the allosteric site to the signaling surface of the receiver domain NtrC was shown to be mediated by a layer of hub residues. The location of hubs preferentially connected to the allosteric site was found in close agreement with key residues experimentally identified as involved in the signal transmission. The comparison with the networks of the homologues CheY and FixJ highlighted similarities in their dynamics. In particular, we showed that a preorganized network of fragment connections between the allosteric and functional sites exists already in the inactive state of all three proteins. PMID:22071506

  3. Extracting a respiratory signal from raw dynamic PET data that contain tracer kinetics

    NASA Astrophysics Data System (ADS)

    Schleyer, P. J.; Thielemans, K.; Marsden, P. K.

    2014-08-01

    Data driven gating (DDG) methods provide an alternative to hardware based respiratory gating for PET imaging. Several existing DDG approaches obtain a respiratory signal by observing the change in PET-counts within specific regions of acquired PET data. Currently, these methods do not allow for tracer kinetics which can interfere with the respiratory signal and introduce error. In this work, we produced a DDG method for dynamic PET studies that exhibit tracer kinetics. Our method is based on an existing approach that uses frequency-domain analysis to locate regions within raw PET data that are subject to respiratory motion. In the new approach, an optimised non-stationary short-time Fourier transform was used to create a time-varying 4D map of motion affected regions. Additional processing was required to ensure that the relationship between the sign of the respiratory signal and the physical direction of movement remained consistent for each temporal segment of the 4D map. The change in PET-counts within the 4D map during the PET acquisition was then used to generate a respiratory curve. Using 26 min dynamic cardiac NH3 PET acquisitions which included a hardware derived respiratory measurement, we show that tracer kinetics can severely degrade the respiratory signal generated by the original DDG method. In some cases, the transition of tracer from the liver to the lungs caused the respiratory signal to invert. The new approach successfully compensated for tracer kinetics and improved the correlation between the data-driven and hardware based signals. On average, good correlation was maintained throughout the PET acquisitions.

  4. Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling.

    PubMed

    Fusco, Ludovico; Lefort, Riwal; Smith, Kevin; Benmansour, Fethallah; Gonzalez, German; Barillari, Caterina; Rinn, Bernd; Fleuret, Francois; Fua, Pascal; Pertz, Olivier

    2016-01-01

    Rho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal morphodynamics in time-lapse datasets. Feature extraction then quantifies dynamic neurite outgrowth phenotypes. We identify a set of stereotypic neurite outgrowth morphodynamic behaviors in a cultured neuronal cell system. Systematic RNA interference perturbation of a Rho GTPase interactome consisting of 219 proteins reveals a limited set of morphodynamic phenotypes. As proof of concept, we show that loss of function of two distinct RhoA-specific GTPase-activating proteins (GAPs) leads to opposite neurite outgrowth phenotypes. Imaging of RhoA activation dynamics indicates that both GAPs regulate different spatiotemporal Rho GTPase pools, with distinct functions. Our results provide a starting point to dissect spatiotemporal Rho GTPase signaling networks that regulate neurite outgrowth. PMID:26728857

  5. Nodal signaling regulates endodermal cell motility and actin dynamics via Rac1 and Prex1

    PubMed Central

    Housley, Michael P.; Weiner, Orion D.

    2012-01-01

    Embryo morphogenesis is driven by dynamic cell behaviors, including migration, that are coordinated with fate specification and differentiation, but how such coordination is achieved remains poorly understood. During zebrafish gastrulation, endodermal cells sequentially exhibit first random, nonpersistent migration followed by oriented, persistent migration and finally collective migration. Using a novel transgenic line that labels the endodermal actin cytoskeleton, we found that these stage-dependent changes in migratory behavior correlated with changes in actin dynamics. The dynamic actin and random motility exhibited during early gastrulation were dependent on both Nodal and Rac1 signaling. We further identified the Rac-specific guanine nucleotide exchange factor Prex1 as a Nodal target and showed that it mediated Nodal-dependent random motility. Reducing Rac1 activity in endodermal cells caused them to bypass the random migration phase and aberrantly contribute to mesodermal tissues. Together, our results reveal a novel role for Nodal signaling in regulating actin dynamics and migration behavior, which are crucial for endodermal morphogenesis and cell fate decisions. PMID:22945937

  6. Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling

    PubMed Central

    Fusco, Ludovico; Lefort, Riwal; Smith, Kevin; Benmansour, Fethallah; Gonzalez, German; Barillari, Caterina; Rinn, Bernd; Fleuret, Francois; Fua, Pascal

    2016-01-01

    Rho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal morphodynamics in time-lapse datasets. Feature extraction then quantifies dynamic neurite outgrowth phenotypes. We identify a set of stereotypic neurite outgrowth morphodynamic behaviors in a cultured neuronal cell system. Systematic RNA interference perturbation of a Rho GTPase interactome consisting of 219 proteins reveals a limited set of morphodynamic phenotypes. As proof of concept, we show that loss of function of two distinct RhoA-specific GTPase-activating proteins (GAPs) leads to opposite neurite outgrowth phenotypes. Imaging of RhoA activation dynamics indicates that both GAPs regulate different spatiotemporal Rho GTPase pools, with distinct functions. Our results provide a starting point to dissect spatiotemporal Rho GTPase signaling networks that regulate neurite outgrowth. PMID:26728857

  7. Analysing pore structure dynamic at clod scales: implications for flow and transport

    NASA Astrophysics Data System (ADS)

    Boivin, Pascal

    2014-05-01

    Based on capillary theory and rigid pore flow equations, the assessment and modelling of flow and transport in soils face severe difficulties since decades. These difficulties can be related to some of the assumptions commonly required by the physical background used. In particular, the assumptions of rigidity and homogeneity were not verified in most soils. Attempts to overcome these limitations were developed along with their evidence, e.g. to take into account soil swelling in flow models, to characterize preferential flow, or to correlate the soil physical parameters to soil constituents and their associated properties to better account for spatial variability. The fundamental splitting of the soil porosity into structural and plasma pores makes a consensus in many fields of soil science. This was seldom considered, however, as a basis for soil physical behaviour modelling, so far. Nevertheless, the mathematical bases for this are deciphered in recent works. Today, the quantification and modelling of these pore systems and their dynamics according to water content, soil constituents, soil biology and chemistry, or external stress, has greatly improved. These factors show different time and space scale dynamics, which are therefore, extremely important to assess separately. The dynamic of the two pore systems appears to be large according to the different factors and time scales. Contrarily to structural pores, the plasma pores do not allow air entry in most of their water content range, which is of consequence for capillary theory and its applications. The soil shrinkage behaviour appears to be closely related to the content in colloidal constituents, though the relation is different according to the two pore system, which is of consequence to account for spatial variability. The mechanical response to stresses is different for the two pore systems as well. The role of soil organic matter variability and changes is strongly highlighted by these researches

  8. Detection and Measurement of Spin-Dependent Dynamics in Random Telegraph Signals

    NASA Astrophysics Data System (ADS)

    House, M. G.; Xiao, Ming; Guo, GuoPing; Li, HaiOu; Cao, Gang; Rosenthal, M. M.; Jiang, HongWen

    2013-09-01

    A quantum point contact was used to observe single-electron fluctuations of a quantum dot in a GaAs heterostructure. The resulting random telegraph signals (RTS) contain statistical information about the electron spin state if the tunneling dynamics are spin dependent. We develop a statistical method to extract information about spin-dependent dynamics from RTS and use it to demonstrate that these dynamics can be studied in the thermal energy regime. The tunneling rates of each spin state are independently measured in a finite external magnetic field. We confirm previous findings of a decrease in overall tunneling rates for the spin excited state compared to the ground state as an external magnetic field is increased.

  9. Dynamic analyses of a crack run-arrest experiment in a nonisothermal plate

    SciTech Connect

    Bass, B.R.; Pugh, C.E.; Stamm, H.K.

    1985-06-01

    In crack-arrest studies sponsored by the Heavy-Section Steel Technology (HSST) Program, a primary objective has been to produce fracture toughness data for reactor pressure vessel materials at temperatures approaching the Charpy upper-shelf regime. Wide-plate tests being conducted at the National Bureau of Standards for the HSST Program are providing an opportunity to obtain significant numbers of data points at affordable costs. In these tests, a single-edge crack in a wide-plate which is subjected to tensile loading initiates at low temperature and arrests in a region of increased fracture toughness. The gradient in toughness is achieved by applying a linear transverse temperature profile across the plate. The second test in this series for A 533 grade B class 1 steel involves crack initiation in cleavage followed by arrest at a temperature corresponding to Charpy upper-shelf behavior. The plate geometry, the material properties, and the instrumentation are discussed along with conditions and results for this test. Pretest static and elastodynamic analyses are described, and posttest analyses based on actual boundary conditions are shown to compare favorably with the observed run-arrest events.

  10. Dynamic characterization of a lightweight, highly maneuverable spacecraft using modal and finite element analyses

    SciTech Connect

    Manning, P.A.; Burdick, R.B.; Woehrle, T.G.

    1992-11-01

    The Lawrence Livermore National Laboratory is engaged in a technology development project which includes designing a lightweight, autonomous, highly maneuverable space vehicle, commonly referred to as a probe. The current probe design includes a guidance and control system that requires complete information on the dynamic response of the probe during operation. A finite element model of the probe was constructed to provide analytical information on the dynamic response to specific operational inputs. In order to verify the assumptions made in the model, a mass mock-up of the probe was constructed at LLNL and an experimental modal survey was performed to determine the frequencies, damping values and deflection shapes for each natural mode of the mock-up. The experimental modal parameters were compared with the parameters obtained through modal analysis of the finite element model to provide a measure of the correlation between the model and the actual structure. This report describes the experimental modal testing and analysis of the mass mock-up and compares the experimental results with the finite element results.

  11. Dynamics of task-set carry-over: evidence from eye-movement analyses.

    PubMed

    Kikumoto, Atsushi; Hubbard, Jason; Mayr, Ulrich

    2016-06-01

    Trial-to-trial carry-over of task sets (i.e., task-set inertia) is often considered as a primary reason for task-switch costs. Yet, we know little about the dynamics of such carry-over effects, in particular how much they are driven by the most recent trial rather than characterized by a more continuous memory gradient. Using eye-tracking, we examined in a 3-task, switching paradigm whether there is a greater probability of non-target fixations to stimuli associated with the previously relevant attentional set than to those associated with the less-recent set. Indeed, we found strong evidence for more interference (expressed in terms of non-target fixations) from recent than from less-recent tasks and that in particular the interference from pre-switch trials contributed substantially to the overall pattern of response-time switch costs. Moreover, task-set carry-over was dominated by the most-recent trial when subjects could expect task repetitions (with a 33 % switch rate). In comparison, when tasks were selected randomly (with a 66 % switch rate), interference from the most recent trial decreased, whereas interference from less-recent trials increased. In sum, carry-over interference dynamics were characterized both by a gradual recency gradient and expectations about task-transition probabilities. Beyond that, there was little evidence for a unique role of the most-recent trial. PMID:26415999

  12. Mother-Infant Verbal and Nonverbal Interaction as Predictor of Attachment: Nonlinear Dynamic Analyses.

    PubMed

    Cerezo, M Angeles; Pons-Salvador, Gemma; Trenado, Rosa M; Sierra, Purificacion

    2016-10-01

    This longitudinal study examined flexibility in early mother-infant interaction at the age of approximately 6 months (N=30) and whether flexibility indices predicted (in) secure child attachment at 15 months. Dyadic flexibility was measured using dynamic systems-based modelling of patterns during mother-child free play in terms of NDS variables derived from SSG: the propensity to change states (dynamic flexibility), number of states visited (diversity) and predictability (dispersion). Results showed significant discriminant functions on the attachment type groups, A, B & C, for the total grid, which included verbal and non-verbal, and for the reciprocal verbal region. Specifically, the prediction outcomes seem to work better in total grid for A-dyads and in the reciprocal verbal region for B and C-dyads. Diversity emerged as the most relevant index in dyadic flexibility: A-dyads showed the least diversity, distinguished them from B-dyads in the verbal regions, (both the reciprocal and non-reciprocal, 'child verbal-mother non-verbal' one), and, from C-dyads in the reciprocal non-verbal region. A-dyads showed remarkably low activity in the regions involving child verbal behavior, showing that children who became avoidant attached at 15 months of age, were mostly silent at approximately 6 months, when they interacted with their mothers. Findings in this study contribute to advancing conceptually informed measurement of dyadic interaction to provide a new perspective on maternal sensitivity and early markers of child insecure/secure attachment. PMID:27550705

  13. A digital-signal-processor-based optical tomographic system for dynamic imaging of joint diseases

    NASA Astrophysics Data System (ADS)

    Lasker, Joseph M.

    Over the last decade, optical tomography (OT) has emerged as viable biomedical imaging modality. Various imaging systems have been developed that are employed in preclinical as well as clinical studies, mostly targeting breast imaging, brain imaging, and cancer related studies. Of particular interest are so-called dynamic imaging studies where one attempts to image changes in optical properties and/or physiological parameters as they occur during a system perturbation. To successfully perform dynamic imaging studies, great effort is put towards system development that offers increasingly enhanced signal-to-noise performance at ever shorter data acquisition times, thus capturing high fidelity tomographic data within narrower time periods. Towards this goal, I have developed in this thesis a dynamic optical tomography system that is, unlike currently available analog instrumentation, based on digital data acquisition and filtering techniques. At the core of this instrument is a digital signal processor (DSP) that collects, collates, and processes the digitized data set. Complementary protocols between the DSP and a complex programmable logic device synchronizes the sampling process and organizes data flow. Instrument control is implemented through a comprehensive graphical user interface which integrates automated calibration, data acquisition, and signal post-processing. Real-time data is generated at frame rates as high as 140 Hz. An extensive dynamic range (˜190 dB) accommodates a wide scope of measurement geometries and tissue types. Performance analysis demonstrates very low system noise (˜1 pW rms noise equivalent power), excellent signal precision (˜0.04%--0.2%) and long term system stability (˜1% over 40 min). Experiments on tissue phantoms validate spatial and temporal accuracy of the system. As a potential new application of dynamic optical imaging I present the first application of this method to use vascular hemodynamics as a means of characterizing

  14. Dynamic mesolimbic dopamine signaling during action sequence learning and expectation violation.

    PubMed

    Collins, Anne L; Greenfield, Venuz Y; Bye, Jeffrey K; Linker, Kay E; Wang, Alice S; Wassum, Kate M

    2016-01-01

    Prolonged mesolimbic dopamine concentration changes have been detected during spatial navigation, but little is known about the conditions that engender this signaling profile or how it develops with learning. To address this, we monitored dopamine concentration changes in the nucleus accumbens core of rats throughout acquisition and performance of an instrumental action sequence task. Prolonged dopamine concentration changes were detected that ramped up as rats executed each action sequence and declined after earned reward collection. With learning, dopamine concentration began to rise increasingly earlier in the execution of the sequence and ultimately backpropagated away from stereotyped sequence actions, becoming only transiently elevated by the most distal and unexpected reward predictor. Action sequence-related dopamine signaling was reactivated in well-trained rats if they became disengaged in the task and in response to an unexpected change in the value, but not identity of the earned reward. Throughout training and test, dopamine signaling correlated with sequence performance. These results suggest that action sequences can engender a prolonged mode of dopamine signaling in the nucleus accumbens core and that such signaling relates to elements of the motivation underlying sequence execution and is dynamic with learning, overtraining and violations in reward expectation. PMID:26869075

  15. A parallel unbalanced digitization architecture to reduce the dynamic range of multiple signals

    NASA Astrophysics Data System (ADS)

    Vallérian, Mathieu; HuÅ£u, Florin; Villemaud, Guillaume; Miscopein, Benoît; Risset, Tanguy

    2016-05-01

    Technologies employed in urban sensor networks are permanently evolving, and thus the gateways employed to collect data in such kind of networks have to be very flexible in order to be compliant with the new communication standards. A convenient way to do that is to digitize all the received signals in one shot and then to digitally perform the signal processing, as it is done in software-defined radio (SDR). All signals can be emitted with very different features (bandwidth, modulation type, and power level) in order to respond to the various propagation conditions. Their difference in terms of power levels is a problem when digitizing them together, as no current commercial analog-to-digital converter (ADC) can provide a fine enough resolution to digitize this high dynamic range between the weakest possible signal in the presence of a stronger signal. This paper presents an RF front end receiver architecture capable of handling this problem by using two ADCs of lower resolutions. The architecture is validated through a set of simulations using Keysight's ADS software. The main validation criterion is the bit error rate comparison with a classical receiver.

  16. A robust color signal processing with wide dynamic range WRGB CMOS image sensor

    NASA Astrophysics Data System (ADS)

    Kawada, Shun; Kuroda, Rihito; Sugawa, Shigetoshi

    2011-01-01

    We have developed a robust color reproduction methodology by a simple calculation with a new color matrix using the formerly developed wide dynamic range WRGB lateral overflow integration capacitor (LOFIC) CMOS image sensor. The image sensor was fabricated through a 0.18 μm CMOS technology and has a 45 degrees oblique pixel array, the 4.2 μm effective pixel pitch and the W pixels. A W pixel was formed by replacing one of the two G pixels in the Bayer RGB color filter. The W pixel has a high sensitivity through the visible light waveband. An emerald green and yellow (EGY) signal is generated from the difference between the W signal and the sum of RGB signals. This EGY signal mainly includes emerald green and yellow lights. These colors are difficult to be reproduced accurately by the conventional simple linear matrix because their wave lengths are in the valleys of the spectral sensitivity characteristics of the RGB pixels. A new linear matrix based on the EGY-RGB signal was developed. Using this simple matrix, a highly accurate color processing with a large margin to the sensitivity fluctuation and noise has been achieved.

  17. Dynamic mesolimbic dopamine signaling during action sequence learning and expectation violation

    PubMed Central

    Collins, Anne L.; Greenfield, Venuz Y.; Bye, Jeffrey K.; Linker, Kay E.; Wang, Alice S.; Wassum, Kate M.

    2016-01-01

    Prolonged mesolimbic dopamine concentration changes have been detected during spatial navigation, but little is known about the conditions that engender this signaling profile or how it develops with learning. To address this, we monitored dopamine concentration changes in the nucleus accumbens core of rats throughout acquisition and performance of an instrumental action sequence task. Prolonged dopamine concentration changes were detected that ramped up as rats executed each action sequence and declined after earned reward collection. With learning, dopamine concentration began to rise increasingly earlier in the execution of the sequence and ultimately backpropagated away from stereotyped sequence actions, becoming only transiently elevated by the most distal and unexpected reward predictor. Action sequence-related dopamine signaling was reactivated in well-trained rats if they became disengaged in the task and in response to an unexpected change in the value, but not identity of the earned reward. Throughout training and test, dopamine signaling correlated with sequence performance. These results suggest that action sequences can engender a prolonged mode of dopamine signaling in the nucleus accumbens core and that such signaling relates to elements of the motivation underlying sequence execution and is dynamic with learning, overtraining and violations in reward expectation. PMID:26869075

  18. Decoupling negative damping signals in a power system through dynamic gain reduction measures

    SciTech Connect

    Coowar, F.; Magdy, M.A. ); Grainger, W. )

    1992-08-01

    Low frequency oscillations occurring in a power system can be accentuated in generators through a feedback loop which connects the output of the system to the summing junction of the Automatic Voltage Regulator (AVR) where the Power System Stabilizer (PSS) is also connected. A method of decoupling these oscillations without compromising the benevolent effects of other control loops in that system is presented. A notch filter, located in the forward path of the negative damping signal, provides the necessary Dynamic Gain Reduction (DGR) for switching off the detrimental signals. This paper provides relevant frequency domain analysis of the closed loop transfer function of a typical power system which reflects the effect of tie-line disturbances on power angle oscillations. This leads to a restructuring of the transfer blocks in the system and the design of a DGR block that allows the decoupling of the negative damping signals. Additional insight into the effect of negative damping signals and their subsequent decoupling is provided through the examination of loop and transfer block signals.

  19. The relation of signal transduction to the sensitivity and dynamic range of bacterial chemotaxis.

    PubMed

    Namba, Toshinori; Nishikawa, Masatoshi; Shibata, Tatsuo

    2012-09-19

    Complex networks of interacting molecular components of living cells are responsible for many important processes, such as signal processing and transduction. An important challenge is to understand how the individual properties of these molecular interactions and biochemical transformations determine the system-level properties of biological functions. Here, we address the issue of the accuracy of signal transduction performed by a bacterial chemotaxis system. The chemotaxis sensitivity of bacteria to a chemoattractant gradient has been measured experimentally from bacterial aggregation in a chemoattractant-containing capillary. The observed precision of the chemotaxis depended on environmental conditions such as the concentration and molecular makeup of the chemoattractant. In a quantitative model, we derived the chemotactic response function, which is essential to describing the signal transduction process involved in bacterial chemotaxis. In the presence of a gradient, an analytical solution is derived that reveals connections between the chemotaxis sensitivity and the characteristics of the signaling system, such as reaction rates. These biochemical parameters are integrated into two system-level parameters: one characterizes the efficiency of gradient sensing, and the other is related to the dynamic range of chemotaxis. Thus, our approach explains how a particular signal transduction property affects the system-level performance of bacterial chemotaxis. We further show that the two parameters can be derived from published experimental data from a capillary assay, which successfully characterizes the performance of bacterial chemotaxis. PMID:22995512

  20. Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency

    PubMed Central

    Cacchiarelli, Davide; Trapnell, Cole; Ziller, Michael J.; Soumillon, Magali; Cesana, Marcella; Karnik, Rahul; Donaghey, Julie; Smith, Zachary D.; Ratanasirintrawoot, Sutheera; Zhang, Xiaolan; Ho Sui, Shannan J.; Wu, Zhaoting; Akopian, Veronika; Gifford, Casey A.; Doench, John; Rinn, John L.; Daley, George Q.; Meissner, Alexander; Lander, Eric S.; Mikkelsen, Tarjei S.

    2015-01-01

    Summary Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered reactivation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. PMID:26186193

  1. Approaches to analyse dynamic microbial communities such as those seen in cystic fibrosis lung

    PubMed Central

    2009-01-01

    Microbial communities play vital roles in many aspects of our lives, although our understanding of microbial biogeography and community profiles remains unclear. The number of microbes or the diversity of the microbes, even in small environmental niches, is staggering. Current microbiological methods used to analyse these communities are limited, in that many microorganisms cannot be cultured. Even for the isolates that can be cultured, the expense of identifying them definitively is much too high to be practical. Many recent molecular technologies, combined with bioinformatic tools, are raising the bar by improving the sensitivity and reliability of microbial community analysis. These tools and techniques range from those that attempt to understand a microbial community from their length heterogeneity profiles to those that help to identify the strains and species of a random sampling of the microbes in a given sample. These technologies are reviewed here, using the microbial communities present in the lungs of cystic fibrosis patients as a paradigm. PMID:19403459

  2. Dynamic interaction between retinal and extraretinal signals in motion integration for smooth pursuit.

    PubMed

    Bogadhi, Amarender R; Montagnini, Anna; Masson, Guillaume S

    2013-01-01

    Due to the aperture problem, the initial direction of tracking responses to a translating bar is biased towards the direction orthogonal to the bar. This observation offers a powerful way to explore the interactions between retinal and extraretinal signals in controlling our actions. We conducted two experiments to probe these interactions by briefly (200 and 400 ms) blanking the moving target (45° or 135° tilted bar) during steady state (Experiment 1) and at different moments during the early phase of pursuit (Experiment 2). In Experiment 1, we found a marginal but statistically significant directional bias on target reappearance for all subjects in at least one blank condition (200 or 400 ms). In Experiment 2, no systematic significant directional bias was observed at target reappearance after a blank. These results suggest that the weighting of retinal and extraretinal signals is dynamically modulated during the different phases of pursuit. Based on our previous theoretical work on motion integration, we propose a new closed-loop two-stage recurrent Bayesian model where retinal and extraretinal signals are dynamically weighted based on their respective reliabilities and combined to compute the visuomotor drive. With a single free parameter, the model reproduces many aspects of smooth pursuit observed across subjects during and immediately after target blanking. It provides a new theoretical framework to understand how different signals are dynamically combined based on their relative reliability to adaptively control our actions. Overall, the model and behavioral results suggest that human subjects rely more strongly on prediction during the early phase than in the steady state phase of pursuit. PMID:24190910

  3. Mothers' Emotion Dynamics and Their Relations With Harsh and Lax Discipline: Microsocial Time Series Analyses

    PubMed Central

    Lorber, Michael F.

    2006-01-01

    Hypotheses were tested about how moment-by-moment variation in mothers' negative emotion predicts harsh and lax discipline. Mother–toddler dyads interacted in a task designed to elicit challenging child behavior. Mothers viewed videotapes of their interactions and continuously rated their experienced emotion. Harsh discipline was associated with mothers' greater negative emotion intensity, greater dependence of mothers' emotion on toddlers' negative affect, and lower serial predictability of mothers' emotion. Laxness was also associated with greater emotion dependence on negative toddler affect and lower serial predictability but not with negative emotion intensity. The dependence of mothers' emotion on toddlers' rule violations was not associated with discipline. Dynamic emotion variables were not redundant with emotion intensity and therefore enhance our understanding of the role of emotion in discipline. PMID:16026219

  4. Descriptive and sensitivity analyses of WATBALI: A dynamic soil water model

    NASA Technical Reports Server (NTRS)

    Hildreth, W. W. (Principal Investigator)

    1981-01-01

    A soil water computer model that uses the IBM Continuous System Modeling Program III to solve the dynamic equations representing the soil, plant, and atmospheric physical or physiological processes considered is presented and discussed. Using values describing the soil-plant-atmosphere characteristics, the model predicts evaporation, transpiration, drainage, and soil water profile changes from an initial soil water profile and daily meteorological data. The model characteristics and simulations that were performed to determine the nature of the response to controlled variations in the input are described the results of the simulations are included and a change that makes the response of the model more closely represent the observed characteristics of evapotranspiration and profile changes for dry soil conditions is examined.

  5. Dynamic Analyses of Result Quality in Energy-Aware Approximate Programs

    NASA Astrophysics Data System (ADS)

    RIngenburg, Michael F.

    Energy efficiency is a key concern in the design of modern computer systems. One promising approach to energy-efficient computation, approximate computing, trades off output precision for energy efficiency. However, this tradeoff can have unexpected effects on computation quality. This thesis presents dynamic analysis tools to study, debug, and monitor the quality and energy efficiency of approximate computations. We propose three styles of tools: prototyping tools that allow developers to experiment with approximation in their applications, online tools that instrument code to determine the key sources of error, and online tools that monitor the quality of deployed applications in real time. Our prototyping tool is based on an extension to the functional language OCaml. We add approximation constructs to the language, an approximation simulator to the runtime, and profiling and auto-tuning tools for studying and experimenting with energy-quality tradeoffs. We also present two online debugging tools and three online monitoring tools. The first online tool identifies correlations between output quality and the total number of executions of, and errors in, individual approximate operations. The second tracks the number of approximate operations that flow into a particular value. Our online tools comprise three low-cost approaches to dynamic quality monitoring. They are designed to monitor quality in deployed applications without spending more energy than is saved by approximation. Online monitors can be used to perform real time adjustments to energy usage in order to meet specific quality goals. We present prototype implementations of all of these tools and describe their usage with several applications. Our prototyping, profiling, and autotuning tools allow us to experiment with approximation strategies and identify new strategies, our online tools succeed in providing new insights into the effects of approximation on output quality, and our monitors succeed in

  6. Analysing land and vegetation cover dynamics during last three decades in Katerniaghat wildlife sanctuary, India

    NASA Astrophysics Data System (ADS)

    Chitale, V. S.; Behera, M. D.

    2014-10-01

    The change in the tropical forests could be clearly linked to the expansion of the human population and economies. An understanding of the anthropogenic forcing plays an important role in analyzing the impacts of climate change and the fate of tropical forests in the present and future scenario. In the present study, we analyze the impact of natural and anthropogenic factors in forest dynamics in Katerniaghat wildlife sanctuary situated along the Indo-Nepal border in Uttar Pradesh state, India. The study site is under tremendous pressure due to anthropogenic factors from surrounding areas since last three decades. The vegetation cover of the sanctuary primarily comprised of Shorea robusta forests, Tectona grandis plantation, and mixed deciduous forest; while the land cover comprised of agriculture, barren land, and water bodies. The classification accuracy was 83.5%, 91.5%, and 95.2% with MSS, IKONOS, and Quickbird datasets, respectively. Shorea robusta forests showed an increase of 16 km2; while Tectona grandis increased by 63.01 km2 during 1975-2010. The spatial heterogeneity in these tropical vegetation classes surrounded by the human dominated agricultural lands could not be addressed using Landsat MSS data due to coarse spatial resolution; whereas the IKONOS and Quickbird satellite datasets proved to advantageous, thus being able to precisely address the variations within the vegetation classes as well as in the land cover classes and along the edge areas. Massive deforestation during 1970s along the adjoining international boundary with Nepal has led to destruction of the wildlife corridor and has exposed the wildlife sanctuary to human interference like grazing and poaching. Higher rates of forest dynamics during the 25-year period indicate the vulnerability of the ecosystem to the natural and anthropogenic disturbances in the proximity of the sanctuary.

  7. Mapping Transient Hyperventilation Induced Alterations with Estimates of the Multi-Scale Dynamics of BOLD Signal

    PubMed Central

    Kiviniemi, Vesa; Remes, Jukka; Starck, Tuomo; Nikkinen, Juha; Haapea, Marianne; Silven, Olli; Tervonen, Osmo

    2009-01-01

    Temporal blood oxygen level dependent (BOLD) contrast signals in functional MRI during rest may be characterized by power spectral distribution (PSD) trends of the form 1/fα. Trends with 1/f characteristics comprise fractal properties with repeating oscillation patterns in multiple time scales. Estimates of the fractal properties enable the quantification of phenomena that may otherwise be difficult to measure, such as transient, non-linear changes. In this study it was hypothesized that the fractal metrics of 1/f BOLD signal trends can map changes related to dynamic, multi-scale alterations in cerebral blood flow (CBF) after a transient hyperventilation challenge. Twenty-three normal adults were imaged in a resting-state before and after hyperventilation. Different variables (1/f trend constant α, fractal dimension Df, and, Hurst exponent H) characterizing the trends were measured from BOLD signals. The results show that fractal metrics of the BOLD signal follow the fractional Gaussian noise model, even during the dynamic CBF change that follows hyperventilation. The most dominant effect on the fractal metrics was detected in grey matter, in line with previous hyperventilation vaso-reactivity studies. The α was able to differentiate also blood vessels from grey matter changes. Df was most sensitive to grey matter. H correlated with default mode network areas before hyperventilation but this pattern vanished after hyperventilation due to a global increase in H. In the future, resting-state fMRI combined with fractal metrics of the BOLD signal may be used for analyzing multi-scale alterations of cerebral blood flow. PMID:19636388

  8. Parsimony and model-based analyses of indels in avian nuclear genes reveal congruent and incongruent phylogenetic signals.

    PubMed

    Yuri, Tamaki; Kimball, Rebecca T; Harshman, John; Bowie, Rauri C K; Braun, Michael J; Chojnowski, Jena L; Han, Kin-Lan; Hackett, Shannon J; Huddleston, Christopher J; Moore, William S; Reddy, Sushma; Sheldon, Frederick H; Steadman, David W; Witt, Christopher C; Braun, Edward L

    2013-01-01

    Insertion/deletion (indel) mutations, which are represented by gaps in multiple sequence alignments, have been used to examine phylogenetic hypotheses for some time. However, most analyses combine gap data with the nucleotide sequences in which they are embedded, probably because most phylogenetic datasets include few gap characters. Here, we report analyses of 12,030 gap characters from an alignment of avian nuclear genes using maximum parsimony (MP) and a simple maximum likelihood (ML) framework. Both trees were similar, and they exhibited almost all of the strongly supported relationships in the nucleotide tree, although neither gap tree supported many relationships that have proven difficult to recover in previous studies. Moreover, independent lines of evidence typically corroborated the nucleotide topology instead of the gap topology when they disagreed, although the number of conflicting nodes with high bootstrap support was limited. Filtering to remove short indels did not substantially reduce homoplasy or reduce conflict. Combined analyses of nucleotides and gaps resulted in the nucleotide topology, but with increased support, suggesting that gap data may prove most useful when analyzed in combination with nucleotide substitutions. PMID:24832669

  9. In silico analyses of COMT, an important signaling cascade of dopaminergic neurotransmission pathway, for drug development of Parkinson's disease.

    PubMed

    Chakraborty, Chiranjib; Pal, Soumen; Doss, C George Priya; Wen, Zhi-Hong; Lin, Chan-Shing

    2012-06-01

    Catechol-O-methyltransferase (COMT) has a vital role for degradation of dopamine, a neurotransmitter, and this dopamine performs an important function in our mental and physical health. The scarcity of dopamine may lead to Parkinson's disease, and inhibition of COMT can stop dopamine metabolism. Here, we have carried out genomics and proteomics analyses of COMT in order to facilitate new inhibitors of COMT. For genomics analyses, we performed codon composition investigation of COMT gene which shows A+T content which is 53.3 %. For proteomics analyses, conservation patterns and residues (highly conserved amino acids GLU64, LEU65, GLY66, CYS69, GLY70, ALA77, GLU90, THR99, SER119, ASP136, LEU140, ASP141, THR164, ASN170, VAL171, and ILE172), binding grooves, binding pockets, binding and conformation with substrate, evaluation of amino acid composition (15 % leucine rich), high scoring hydrophobic segments, high scoring transmembrane segments, tandem and periodic repeats, and disulfide bonds (three numbers), sequence logos (maximum stack height of 3 b and minimum stack height of <0.5 b) have been investigated for COMT protein. Furthermore, using COMT sequences of different species (class Mammalia, class Amphibia, and class Pisces), a phylogenetic tree has been constructed to examine the evolutionary relationship among different species. PMID:22622642

  10. Signaling and Dynamic Actin Responses of B Cells on Topographical Substrates

    NASA Astrophysics Data System (ADS)

    Ketchum, Christina; Sun, Xiaoyu; Fourkas, John; Song, Wenxia; Upadhyaya, Arpita

    B cells become activated upon physical contact with antigen on the surface of antigen presenting cells, such as dendritic cells. Binding of the B cell receptor with antigen initiates actin-mediated spreading of B cells, signaling cascades and eventually infection fighting antibodies. Lymphocytes, including B cells and T cells, have been shown to be responsive to the physical parameters of the contact surface, such as antigen mobility and substrate stiffness. However the roll of surface topography on lymphocyte function is unknown. Here we investigate the degree to which substrate topography controls actin-mediated spreading and B cell activation using nano-fabricated surfaces and live cell imaging. The model topographical system consists of 600 nanometer tall ridges with spacing varying between 800 nanometers and 5 micrometers. Using TIRF imaging we observe actin dynamics, B cell receptor motion and calcium signaling of B cells as they spread on the ridged substrates. We show that the spacing between ridges had a strong effect on the dynamics of actin and calcium influx on B cells. Our results indicate that B cells are highly sensitive to surface topography during cell spreading and signaling activation.

  11. Advances in dynamic modeling of colorectal cancer signaling-network regions, a path toward targeted therapies

    PubMed Central

    Kolch, Walter; Kholodenko, Boris N.; Ambrosi, Cristina De; Barla, Annalisa; Biganzoli, Elia M.; Nencioni, Alessio; Patrone, Franco; Ballestrero, Alberto; Zoppoli, Gabriele; Verri, Alessandro; Parodi, Silvio

    2015-01-01

    The interconnected network of pathways downstream of the TGFβ, WNT and EGF-families of receptor ligands play an important role in colorectal cancer pathogenesis. We studied and implemented dynamic simulations of multiple downstream pathways and described the section of the signaling network considered as a Molecular Interaction Map (MIM). Our simulations used Ordinary Differential Equations (ODEs), which involved 447 reactants and their interactions. Starting from an initial “physiologic condition”, the model can be adapted to simulate individual pathologic cancer conditions implementing alterations/mutations in relevant onco-proteins. We verified some salient model predictions using the mutated colorectal cancer lines HCT116 and HT29. We measured the amount of MYC and CCND1 mRNAs and AKT and ERK phosphorylated proteins, in response to individual or combination onco-protein inhibitor treatments. Experimental and simulation results were well correlated. Recent independently published results were also predicted by our model. Even in the presence of an approximate and incomplete signaling network information, a predictive dynamic modeling seems already possible. An important long term road seems to be open and can be pursued further, by incremental steps, toward even larger and better parameterized MIMs. Personalized treatment strategies with rational associations of signaling-proteins inhibitors, could become a realistic goal. PMID:25671297

  12. Applications of elastic-viscoplastic constitutive models in dynamic analyses of crack run-arrest events

    SciTech Connect

    Bass, B.R.; Pugh, C.E.; Swindeman, R.W.

    1986-01-01

    Various viscoplastic constitutive models and several nonlinear fracture criteria are being installed in the ADINA general purpose finite element computer program, and the combined predictive capabilities are being evaluated through applications to the HSST wide-plate experiments. The first two constitutive models selected for installation in ADINA were a variation of the Perzyna elastic-viscoplastic model with linear strain hardening and the Bodner-Partom viscoplastic model with strain hardening. Other models being examined include those due to Robinson-Pugh and Hart. The fracture criteria being examined for use with nonlinear analyses include several path-independent integrals that were formulated to remove limitations on the original J-integral of Rice. Some of these integrals represent slight modifications of the J-integral, while others have a different theoretical basis. This paper describes applications of these nonlinear techniques to the first series of six HSST wide-plate crack-arrest tests that have been performed. These experiments include crack initiations at low temperatures and relatively long (20 cm) cleavage propagation phases which are terminated by arrest in high-temperature regions. Crack arrests are then followed by ductile tearing events. Consequently, the crack-front regions in these tests are exposed to wide ranges of strain rates and temperatures.

  13. Signal transduction controls heterogeneous NF-κB dynamics and target gene expression through cytokine-specific refractory states

    PubMed Central

    Adamson, Antony; Boddington, Christopher; Downton, Polly; Rowe, William; Bagnall, James; Lam, Connie; Maya-Mendoza, Apolinar; Schmidt, Lorraine; Harper, Claire V.; Spiller, David G.; Rand, David A.; Jackson, Dean A.; White, Michael R. H.; Paszek, Pawel

    2016-01-01

    Cells respond dynamically to pulsatile cytokine stimulation. Here we report that single, or well-spaced pulses of TNFα (>100 min apart) give a high probability of NF-κB activation. However, fewer cells respond to shorter pulse intervals (<100 min) suggesting a heterogeneous refractory state. This refractory state is established in the signal transduction network downstream of TNFR and upstream of IKK, and depends on the level of the NF-κB system negative feedback protein A20. If a second pulse within the refractory phase is IL-1β instead of TNFα, all of the cells respond. This suggests a mechanism by which two cytokines can synergistically activate an inflammatory response. Gene expression analyses show strong correlation between the cellular dynamic response and NF-κB-dependent target gene activation. These data suggest that refractory states in the NF-κB system constitute an inherent design motif of the inflammatory response and we suggest that this may avoid harmful homogenous cellular activation. PMID:27381163

  14. Pathway Network Analyses for Autism Reveal Multisystem Involvement, Major Overlaps with Other Diseases and Convergence upon MAPK and Calcium Signaling.

    PubMed

    Wen, Ya; Alshikho, Mohamad J; Herbert, Martha R

    2016-01-01

    We used established databases in standard ways to systematically characterize gene ontologies, pathways and functional linkages in the large set of genes now associated with autism spectrum disorders (ASDs). These conditions are particularly challenging--they lack clear pathognomonic biological markers, they involve great heterogeneity across multiple levels (genes, systemic biological and brain characteristics, and nuances of behavioral manifestations)-and yet everyone with this diagnosis meets the same defining behavioral criteria. Using the human gene list from Simons Foundation Autism Research Initiative (SFARI) we performed gene set enrichment analysis with the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database, and then derived a pathway network from pathway-pathway functional interactions again in reference to KEGG. Through identifying the GO (Gene Ontology) groups in which SFARI genes were enriched, mapping the coherence between pathways and GO groups, and ranking the relative strengths of representation of pathway network components, we 1) identified 10 disease-associated and 30 function-associated pathways 2) revealed calcium signaling pathway and neuroactive ligand-receptor interaction as the most enriched, statistically significant pathways from the enrichment analysis, 3) showed calcium signaling pathways and MAPK signaling pathway to be interactive hubs with other pathways and also to be involved with pervasively present biological processes, 4) found convergent indications that the process "calcium-PRC (protein kinase C)-Ras-Raf-MAPK/ERK" is likely a major contributor to ASD pathophysiology, and 5) noted that perturbations associated with KEGG's category of environmental information processing were common. These findings support the idea that ASD-associated genes may contribute not only to core features of ASD themselves but also to vulnerability to other chronic and systemic problems potentially including cancer, metabolic conditions

  15. Pathway Network Analyses for Autism Reveal Multisystem Involvement, Major Overlaps with Other Diseases and Convergence upon MAPK and Calcium Signaling

    PubMed Central

    Wen, Ya; Alshikho, Mohamad J.; Herbert, Martha R.

    2016-01-01

    We used established databases in standard ways to systematically characterize gene ontologies, pathways and functional linkages in the large set of genes now associated with autism spectrum disorders (ASDs). These conditions are particularly challenging—they lack clear pathognomonic biological markers, they involve great heterogeneity across multiple levels (genes, systemic biological and brain characteristics, and nuances of behavioral manifestations)—and yet everyone with this diagnosis meets the same defining behavioral criteria. Using the human gene list from Simons Foundation Autism Research Initiative (SFARI) we performed gene set enrichment analysis with the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database, and then derived a pathway network from pathway-pathway functional interactions again in reference to KEGG. Through identifying the GO (Gene Ontology) groups in which SFARI genes were enriched, mapping the coherence between pathways and GO groups, and ranking the relative strengths of representation of pathway network components, we 1) identified 10 disease-associated and 30 function-associated pathways 2) revealed calcium signaling pathway and neuroactive ligand-receptor interaction as the most enriched, statistically significant pathways from the enrichment analysis, 3) showed calcium signaling pathways and MAPK signaling pathway to be interactive hubs with other pathways and also to be involved with pervasively present biological processes, 4) found convergent indications that the process “calcium-PRC (protein kinase C)-Ras-Raf-MAPK/ERK” is likely a major contributor to ASD pathophysiology, and 5) noted that perturbations associated with KEGG’s category of environmental information processing were common. These findings support the idea that ASD-associated genes may contribute not only to core features of ASD themselves but also to vulnerability to other chronic and systemic problems potentially including cancer, metabolic

  16. On protection of Freedom's solar dynamic radiator from the orbital debris environment. Part 1: Preliminary analyses and testing

    NASA Technical Reports Server (NTRS)

    Rhatigan, Jennifer L.; Christiansen, Eric L.; Fleming, Michael L.

    1990-01-01

    A great deal of experimentation and analysis was performed to quantify penetration thresholds of components which will experience orbital debris impacts. Penetration was found to depend upon mission specific parameters such as orbital altitude, inclination, and orientation of the component; and upon component specific parameters such as material, density and the geometry particular to its shielding. Experimental results are highly dependent upon shield configuration and cannot be extrapolated with confidence to alternate shield configurations. Also, current experimental capabilities are limited to velocities which only approach the lower limit of predicted orbital debris velocities. Therefore, prediction of the penetrating particle size for a particular component having a complex geometry remains highly uncertain. An approach is described which was developed to assess on-orbit survivability of the solar dynamic radiator due to micrometeoroid and space debris impacts. Preliminary analyses are presented to quantify the solar dynamic radiator survivability, and include the type of particle and particle population expected to defeat the radiator bumpering (i.e., penetrate a fluid flow tube). Results of preliminary hypervelocity impact testing performed on radiator panel samples (in the 6 to 7 km/sec velocity range) are also presented. Plans for further analyses and testing are discussed. These efforts are expected to lead to a radiator design which will perform to requirements over the expected lifetime.

  17. On protection of Freedom's solar dynamic radiator from the orbital debris environment. Part 1. Preliminary analyses and testing

    SciTech Connect

    Rhatigan, J.L.; Christiansen, E.L.; Fleming, M.L.

    1990-01-01

    A great deal of experimentation and analysis was performed to quantify penetration thresholds of components which will experience orbital debris impacts. Penetration was found to depend upon mission specific parameters such as orbital altitude, inclination, and orientation of the component; and upon component specific parameters such as material, density and the geometry particular to its shielding. Experimental results are highly dependent upon shield configuration and cannot be extrapolated with confidence to alternate shield configurations. Also, current experimental capabilities are limited to velocities which only approach the lower limit of predicted orbital debris velocities. Therefore, prediction of the penetrating particle size for a particular component having a complex geometry remains highly uncertain. An approach is described which was developed to assess on-orbit survivability of the solar dynamic radiator due to micrometeoroid and space debris impacts. Preliminary analyses are presented to quantify the solar dynamic radiator survivability, and include the type of particle and particle population expected to defeat the radiator bumpering (i.e., penetrate a fluid flow tube). Results of preliminary hypervelocity impact testing performed on radiator panel samples (in the 6 to 7 km/sec velocity range) are also presented. Plans for further analyses and testing are discussed. These efforts are expected to lead to a radiator design which will perform to requirements over the expected lifetime.

  18. Computational Fluid Dynamics Analyses on Very High Temperature Reactor Air Ingress

    SciTech Connect

    Chang H Oh; Eung S. Kim; Richard Schultz; David Petti; Hyung S. Kang

    2009-07-01

    A preliminary computational fluid dynamics (CFD) analysis was performed to understand density-gradient-induced stratified flow in a Very High Temperature Reactor (VHTR) air-ingress accident. Various parameters were taken into consideration, including turbulence model, core temperature, initial air mole-fraction, and flow resistance in the core. The gas turbine modular helium reactor (GT-MHR) 600 MWt was selected as the reference reactor and it was simplified to be 2-D geometry in modeling. The core and the lower plenum were assumed to be porous bodies. Following the preliminary CFD results, the analysis of the air-ingress accident has been performed by two different codes: GAMMA code (system analysis code, Oh et al. 2006) and FLUENT CFD code (Fluent 2007). Eventually, the analysis results showed that the actual onset time of natural convection (~160 sec) would be significantly earlier than the previous predictions (~150 hours) calculated based on the molecular diffusion air-ingress mechanism. This leads to the conclusion that the consequences of this accident will be much more serious than previously expected.

  19. Rosetta lander Philae: Flight Dynamics analyses for landing site selection and post-landing operations

    NASA Astrophysics Data System (ADS)

    Jurado, Eric; Martin, Thierry; Canalias, Elisabet; Blazquez, Alejandro; Garmier, Romain; Ceolin, Thierry; Gaudon, Philippe; Delmas, Cedric; Biele, Jens; Ulamec, Stephan; Remetean, Emile; Torres, Alex; Laurent-Varin, Julien; Dolives, Benoit; Herique, Alain; Rogez, Yves; Kofman, Wlodek; Jorda, Laurent; Zakharov, Vladimir; Crifo, Jean-François; Rodionov, Alexander; Heinish, P.; Vincent, Jean-Baptiste

    2016-08-01

    On the 12th of November 2014, The Rosetta Lander Philae became the first spacecraft to softly land on a comet nucleus. Due to the double failure of the cold gas hold-down thruster and the anchoring harpoons that should have fixed Philae to the surface, it spent approximately two hours bouncing over the comet surface to finally come at rest one km away from its target site. Nevertheless it was operated during the 57 h of its First Science Sequence. The FSS, performed with the two batteries, should have been followed by the Long Term Science Sequence but Philae was in a place not well illuminated and fell into hibernation. Yet, thanks to reducing distance to the Sun and to seasonal effect, it woke up at end of April and on 13th of June it contacted Rosetta again. To achieve this successful landing, an intense preparation work had been carried out mainly between August and November 2014 to select the targeted landing site and define the final landing trajectory. After the landing, the data collected during on-comet operations have been used to assess the final position and orientation of Philae, and to prepare the wake-up. This paper addresses the Flight Dynamics studies done in the scope of this landing preparation from Lander side, in close cooperation with the team at ESA, responsible for Rosetta, as well as for the reconstruction of the bouncing trajectory and orientation of the Lander after touchdown.

  20. Variability of a dynamic visual signal: the fiddler crab claw-waving display.

    PubMed

    How, Martin J; Zeil, Jochen; Hemmi, Jan M

    2009-01-01

    Fiddler crabs use elaborate, species-specific claw-waving displays to communicate with rivals and mates. However, detailed comparative studies of fiddler crab signal structure and structural variations are lacking. This paper provides an analysis of the claw-waving displays of seven Australian species of fiddler crab, Uca mjoebergi, U. perplexa, U. polita, U. seismella, U. signata, U. elegans and U. vomeris. We used digital video to record and analyse the fine-scale spatiotemporal properties of these movement-based visual signals. We found that the structure and timing of the displays is species-specific, exhibiting inter-specific differences that follow phylogenetic relationships. The displays showed intra-specific variation according to individual identity, geographic location and fine-scale behavioural context. The observed differences and variations are discussed in the light of the evolutionary forces that may shape their design. PMID:19002693

  1. Genetic diversity of Chikungunya virus, India 2006-2010: evolutionary dynamics and serotype analyses.

    PubMed

    Sumathy, K; Ella, Krishna M

    2012-03-01

    The genetic diversity of Chikungunya virus (CHIKV) causing recurring outbreaks in India since 2006 was studied. The 2006 epidemic was caused by a virus strain of the East, Central and South African (ECSA) genotype with 226A in the E1 glycoprotein. The variant strain with E1-A226V mutation caused outbreaks since 2007 in the state of Kerala where Aedes albopictus is the abundant mosquito vector. Molecular epidemiology data since 2007 is scarce from other regions of the country. RT-PCR, sequencing and phylogenetic analyses of CHIKV isolates from the 2009 to 2010 epidemics in the States of Tamil Nadu and Andhra Pradesh placed them in a separate clade within the ECSA lineage. The isolates of the study had 226A in the E1 glycoprotein. The isolates had a novel E1-K211E mutation that was under significant positive selection. E1-211E is highly conserved in the Asian genotype of the virus circulated by Aedes aegypti. Unique mutations in E2 glycoprotein were identified. The two sub-lineages of ECSA genotype circulating in India parallel the abundance of Ae. albopictus and Ae. aegypti. Novel mutations in the envelope glycoproteins suggest adaptive evolution of the virus to local vector abundance. Cross neutralization of the virus isolates from recurring Indian epidemics indicated that no distinct serotypes had evolved. The study has provided insights into the origin, distribution and evolutionary adaptation of the virus to local vector abundance in the region that has reportedly, the highest incidence of CHIKV infection in the world. PMID:22246833

  2. Dynamic Bayesian Network Modeling of the Interplay between EGFR and Hedgehog Signaling

    PubMed Central

    Fröhlich, Holger; Bahamondez, Gloria; Götschel, Frank; Korf, Ulrike

    2015-01-01

    Aberrant activation of sonic Hegdehog (SHH) signaling has been found to disrupt cellular differentiation in many human cancers and to increase proliferation. The SHH pathway is known to cross-talk with EGFR dependent signaling. Recent studies experimentally addressed this interplay in Daoy cells, which are presumable a model system for medulloblastoma, a highly malignant brain tumor that predominately occurs in children. Currently ongoing are several clinical trials for different solid cancers, which are designed to validate the clinical benefits of targeting the SHH in combination with other pathways. This has motivated us to investigate interactions between EGFR and SHH dependent signaling in greater depth. To our knowledge, there is no mathematical model describing the interplay between EGFR and SHH dependent signaling in medulloblastoma so far. Here we come up with a fully probabilistic approach using Dynamic Bayesian Networks (DBNs). To build our model, we made use of literature based knowledge describing SHH and EGFR signaling and integrated gene expression (Illumina) and cellular location dependent time series protein expression data (Reverse Phase Protein Arrays). We validated our model by sub-sampling training data and making Bayesian predictions on the left out test data. Our predictions focusing on key transcription factors and p70S6K, showed a high level of concordance with experimental data. Furthermore, the stability of our model was tested by a parametric bootstrap approach. Stable network features were in agreement with published data. Altogether we believe that our model improved our understanding of the interplay between two highly oncogenic signaling pathways in Daoy cells. This may open new perspectives for the future therapy of Hedghog/EGF-dependent solid tumors. PMID:26571415

  3. Dynamic Bayesian Network Modeling of the Interplay between EGFR and Hedgehog Signaling.

    PubMed

    Fröhlich, Holger; Bahamondez, Gloria; Götschel, Frank; Korf, Ulrike

    2015-01-01

    Aberrant activation of sonic Hegdehog (SHH) signaling has been found to disrupt cellular differentiation in many human cancers and to increase proliferation. The SHH pathway is known to cross-talk with EGFR dependent signaling. Recent studies experimentally addressed this interplay in Daoy cells, which are presumable a model system for medulloblastoma, a highly malignant brain tumor that predominately occurs in children. Currently ongoing are several clinical trials for different solid cancers, which are designed to validate the clinical benefits of targeting the SHH in combination with other pathways. This has motivated us to investigate interactions between EGFR and SHH dependent signaling in greater depth. To our knowledge, there is no mathematical model describing the interplay between EGFR and SHH dependent signaling in medulloblastoma so far. Here we come up with a fully probabilistic approach using Dynamic Bayesian Networks (DBNs). To build our model, we made use of literature based knowledge describing SHH and EGFR signaling and integrated gene expression (Illumina) and cellular location dependent time series protein expression data (Reverse Phase Protein Arrays). We validated our model by sub-sampling training data and making Bayesian predictions on the left out test data. Our predictions focusing on key transcription factors and p70S6K, showed a high level of concordance with experimental data. Furthermore, the stability of our model was tested by a parametric bootstrap approach. Stable network features were in agreement with published data. Altogether we believe that our model improved our understanding of the interplay between two highly oncogenic signaling pathways in Daoy cells. This may open new perspectives for the future therapy of Hedghog/EGF-dependent solid tumors. PMID:26571415

  4. Functional consequences of perturbed CXCL12 signal processing: analyses of immature hematopoiesis in GRK6-deficient mice.

    PubMed

    Chudziak, Doreen; Spohn, Gabriele; Karpova, Darja; Dauber, Katrin; Wiercinska, Eliza; Miettinen, Johanna A; Papayannopoulou, Thalia; Bönig, Halvard

    2015-03-15

    Hematopoietic stem and progenitor cells (HSPCs) reside in bone marrow (BM) in an environment rich in CXCL12, the ligand for CXCR4, which is constitutively expressed on all immature hematopoietic cells in BM. This ligand-receptor pair critically controls HSPC retention and (relative) quiescence in BM. Interestingly, in a chemokine-abundant environment, CXCR4 surface expression and CXCL12 sensitivity of BM-residing HSPCs are continuously maintained. The mechanisms underlying this peculiar pattern of G-protein signal integration by BM-HSPCs are unknown. G-protein receptor kinases (GRKs) control receptor function by phosphorylating the intracellular domains upon ligand-induced activation, which results in receptor internalization and transient refractoriness. Using, therefore, a GRK6-deficient (GRK6(-/-)) mouse, we sought to address how perturbed ligand-induced CXCR4 (in)activation affects HSPC behavior in vitro and in vivo. In vitro, GRK6(-/-) HSPCs were characterized by hyper-responsiveness to CXCL12, as expected. In vivo, GRK6(-/-) immature hematopoiesis was characterized by a marked expansion of immature hematopoiesis in spleens and a modest repopulation defect in serial competitive transplantation. Enforced mobilization with granulocyte colony-stimulating factor (G-CSF) and AMD3100 was normal, as was hematopoietic regeneration after noncompetitive transplantation or pharmacological myelosuppression. These observations illustrate that GRK-mediated restriction of CXCR4 signal input after ligand engagement is largely dispensable for BM-resident HSPCs, which may explain how continuous CXCL12 responsiveness of BM-HSPCs can be maintained. PMID:25316534

  5. Enhanced resting-state dynamics of the hemoglobin signal as a novel biomarker for detection of breast cancer

    SciTech Connect

    Graber, Harry L. Xu, Yong; Barbour, Randall L.; Al abdi, Rabah; Asarian, Armand P.; Pappas, Peter J.; Dresner, Lisa; Patel, Naresh; Jagarlamundi, Kuppuswamy; Solomon, William B.

    2015-11-15

    Purpose: The work presented here demonstrates an application of diffuse optical tomography (DOT) to the problem of breast-cancer diagnosis. The potential for using spatial and temporal variability measures of the hemoglobin signal to identify useful biomarkers was studied. Methods: DOT imaging data were collected using two instrumentation platforms the authors developed, which were suitable for exploring tissue dynamics while performing a simultaneous bilateral exam. For each component of the hemoglobin signal (e.g., total, oxygenated), the image time series was reduced to eight scalar metrics that were affected by one or more dynamic properties of the breast microvasculature (e.g., average amplitude, amplitude heterogeneity, strength of spatial coordination). Receiver-operator characteristic (ROC) analyses, comparing groups of subjects with breast cancer to various control groups (i.e., all noncancer subjects, only those with diagnosed benign breast pathology, and only those with no known breast pathology), were performed to evaluate the effect of cancer on the magnitudes of the metrics and of their interbreast differences and ratios. Results: For women with known breast cancer, simultaneous bilateral DOT breast measures reveal a marked increase in the resting-state amplitude of the vasomotor response in the hemoglobin signal for the affected breast, compared to the contralateral, noncancer breast. Reconstructed 3D spatial maps of observed dynamics also show that this behavior extends well beyond the tumor border. In an effort to identify biomarkers that have the potential to support clinical aims, a group of scalar quantities extracted from the time series measures was systematically examined. This analysis showed that many of the quantities obtained by computing paired responses from the bilateral scans (e.g., interbreast differences, ratios) reveal statistically significant differences between the cancer-positive and -negative subject groups, while the

  6. Phylogenetic and metagenomic analyses of substrate-dependent bacterial temporal dynamics in microbial fuel cells.

    PubMed

    Zhang, Husen; Chen, Xi; Braithwaite, Daniel; He, Zhen

    2014-01-01

    Understanding the microbial community structure and genetic potential of anode biofilms is key to improve extracellular electron transfers in microbial fuel cells. We investigated effect of substrate and temporal dynamics of anodic biofilm communities using phylogenetic and metagenomic approaches in parallel with electrochemical characterizations. The startup non-steady state anodic bacterial structures were compared for a simple substrate, acetate, and for a complex substrate, landfill leachate, using a single-chamber air-cathode microbial fuel cell. Principal coordinate analysis showed that distinct community structures were formed with each substrate type. The bacterial diversity measured as Shannon index decreased with time in acetate cycles, and was restored with the introduction of leachate. The change of diversity was accompanied by an opposite trend in the relative abundance of Geobacter-affiliated phylotypes, which were acclimated to over 40% of total Bacteria at the end of acetate-fed conditions then declined in the leachate cycles. The transition from acetate to leachate caused a decrease in output power density from 243±13 mW/m2 to 140±11 mW/m2, accompanied by a decrease in Coulombic electron recovery from 18±3% to 9±3%. The leachate cycles selected protein-degrading phylotypes within phylum Synergistetes. Metagenomic shotgun sequencing showed that leachate-fed communities had higher cell motility genes including bacterial chemotaxis and flagellar assembly, and increased gene abundance related to metal resistance, antibiotic resistance, and quorum sensing. These differentially represented genes suggested an altered anodic biofilm community in response to additional substrates and stress from the complex landfill leachate. PMID:25202990

  7. A New Concurrent Multiscale Methodology for Coupling Molecular Dynamics and Finite Element Analyses

    NASA Technical Reports Server (NTRS)

    Yamakov, Vesselin; Saether, Erik; Glaessgen, Edward H/.

    2008-01-01

    The coupling of molecular dynamics (MD) simulations with finite element methods (FEM) yields computationally efficient models that link fundamental material processes at the atomistic level with continuum field responses at higher length scales. The theoretical challenge involves developing a seamless connection along an interface between two inherently different simulation frameworks. Various specialized methods have been developed to solve particular classes of problems. Many of these methods link the kinematics of individual MD atoms with FEM nodes at their common interface, necessarily requiring that the finite element mesh be refined to atomic resolution. Some of these coupling approaches also require simulations to be carried out at 0 K and restrict modeling to two-dimensional material domains due to difficulties in simulating full three-dimensional material processes. In the present work, a new approach to MD-FEM coupling is developed based on a restatement of the standard boundary value problem used to define a coupled domain. The method replaces a direct linkage of individual MD atoms and finite element (FE) nodes with a statistical averaging of atomistic displacements in local atomic volumes associated with each FE node in an interface region. The FEM and MD computational systems are effectively independent and communicate only through an iterative update of their boundary conditions. With the use of statistical averages of the atomistic quantities to couple the two computational schemes, the developed approach is referred to as an embedded statistical coupling method (ESCM). ESCM provides an enhanced coupling methodology that is inherently applicable to three-dimensional domains, avoids discretization of the continuum model to atomic scale resolution, and permits finite temperature states to be applied.

  8. An Embedded Statistical Method for Coupling Molecular Dynamics and Finite Element Analyses

    NASA Technical Reports Server (NTRS)

    Saether, E.; Glaessgen, E.H.; Yamakov, V.

    2008-01-01

    The coupling of molecular dynamics (MD) simulations with finite element methods (FEM) yields computationally efficient models that link fundamental material processes at the atomistic level with continuum field responses at higher length scales. The theoretical challenge involves developing a seamless connection along an interface between two inherently different simulation frameworks. Various specialized methods have been developed to solve particular classes of problems. Many of these methods link the kinematics of individual MD atoms with FEM nodes at their common interface, necessarily requiring that the finite element mesh be refined to atomic resolution. Some of these coupling approaches also require simulations to be carried out at 0 K and restrict modeling to two-dimensional material domains due to difficulties in simulating full three-dimensional material processes. In the present work, a new approach to MD-FEM coupling is developed based on a restatement of the standard boundary value problem used to define a coupled domain. The method replaces a direct linkage of individual MD atoms and finite element (FE) nodes with a statistical averaging of atomistic displacements in local atomic volumes associated with each FE node in an interface region. The FEM and MD computational systems are effectively independent and communicate only through an iterative update of their boundary conditions. With the use of statistical averages of the atomistic quantities to couple the two computational schemes, the developed approach is referred to as an embedded statistical coupling method (ESCM). ESCM provides an enhanced coupling methodology that is inherently applicable to three-dimensional domains, avoids discretization of the continuum model to atomic scale resolution, and permits finite temperature states to be applied.

  9. Dynamic Faraday cup signal analysis and the measurement of energetic ions emitted by plasma focus

    SciTech Connect

    Pestehe, S. J. Mohammadnejad, M.; Irani Mobaraki, S.

    2014-03-15

    A theoretical model is developed to study the signals from a typical dynamic Faraday cup, and using this model the output signals from this structure are obtained. A detailed discussion on the signal structure, using different experimental conditions, is also given. It is argued that there is a possibility of determining the total charge of the generated ion pulse, the maximum velocity of the ions, ion velocity distribution, and the number of ion species for mixed working gases, under certain conditions. In addition, the number of different ionization stages, the number of different pinches in one shot, and the number of different existing acceleration mechanisms can also be determined provided that the mentioned conditions being satisfied. An experiment is carried out on the Filippov type 90 kJ Sahand plasma focus using Ar as the working gas at the pressure of 0.25 Torr. The data from a typical shot are fitted to a signal from the model and the total charge of the related energetic ion pulse is deduced using the values of the obtained fit parameters. Good agreement between the obtained amount of the total charge and the values obtained during other experiments on the same plasma focus device is observed.

  10. Knee joint vibration signal analysis with matching pursuit decomposition and dynamic weighted classifier fusion.

    PubMed

    Cai, Suxian; Yang, Shanshan; Zheng, Fang; Lu, Meng; Wu, Yunfeng; Krishnan, Sridhar

    2013-01-01

    Analysis of knee joint vibration (VAG) signals can provide quantitative indices for detection of knee joint pathology at an early stage. In addition to the statistical features developed in the related previous studies, we extracted two separable features, that is, the number of atoms derived from the wavelet matching pursuit decomposition and the number of significant signal turns detected with the fixed threshold in the time domain. To perform a better classification over the data set of 89 VAG signals, we applied a novel classifier fusion system based on the dynamic weighted fusion (DWF) method to ameliorate the classification performance. For comparison, a single leastsquares support vector machine (LS-SVM) and the Bagging ensemble were used for the classification task as well. The results in terms of overall accuracy in percentage and area under the receiver operating characteristic curve obtained with the DWF-based classifier fusion method reached 88.76% and 0.9515, respectively, which demonstrated the effectiveness and superiority of the DWF method with two distinct features for the VAG signal analysis. PMID:23573175

  11. Similarity analysis of voice signals using wavelets with dynamic time warping

    NASA Astrophysics Data System (ADS)

    Tashakkori, Rahman; Bowers, Courtney

    2003-04-01

    Accurately recognizing speech is a difficult task. Differences in gender, accent, pace, tone, as well as defects in the recording equipment and environmental noise can disturb a voice signal. Speech recognition systems are commonly studied and implemented by companies trying to alleviate problems, such as illness or injury, or to increase overall efficiency. This research uses wavelet analysis with several traditional methods to study similarities among sound signals. Through a series of seven steps, a similarity analysis of some voice signals from the same speaker as well as from different speakers is performed. The efficiency of four different wavelets (Haar, db2, db4 and Discrete Morlet), different correlation methods developed previously or in this research, and two different Dynamic Time Warping methods are studied in this research. Through several experiments, it will be shown that these techniques produce excellent results for signals by the same speaker. Based on the limited number of cases studied in this research, some evidence will be presented that suggests the proposed methods on this research are more effective for recognizing male voice files than those of females.

  12. Aurora A drives early signalling and vesicle dynamics during T-cell activation

    PubMed Central

    Blas-Rus, Noelia; Bustos-Morán, Eugenio; Pérez de Castro, Ignacio; de Cárcer, Guillermo; Borroto, Aldo; Camafeita, Emilio; Jorge, Inmaculada; Vázquez, Jesús; Alarcón, Balbino; Malumbres, Marcos; Martín-Cófreces, Noa B.; Sánchez-Madrid, Francisco

    2016-01-01

    Aurora A is a serine/threonine kinase that contributes to the progression of mitosis by inducing microtubule nucleation. Here we have identified an unexpected role for Aurora A kinase in antigen-driven T-cell activation. We find that Aurora A is phosphorylated at the immunological synapse (IS) during TCR-driven cell contact. Inhibition of Aurora A with pharmacological agents or genetic deletion in human or mouse T cells severely disrupts the dynamics of microtubules and CD3ζ-bearing vesicles at the IS. The absence of Aurora A activity also impairs the activation of early signalling molecules downstream of the TCR and the expression of IL-2, CD25 and CD69. Aurora A inhibition causes delocalized clustering of Lck at the IS and decreases phosphorylation levels of tyrosine kinase Lck, thus indicating Aurora A is required for maintaining Lck active. These findings implicate Aurora A in the propagation of the TCR activation signal. PMID:27091106

  13. Dynamic BMP signaling polarized by Toll patterns the dorsoventral axis in a hemimetabolous insect.

    PubMed

    Sachs, Lena; Chen, Yen-Ta; Drechsler, Axel; Lynch, Jeremy A; Panfilio, Kristen A; Lässig, Michael; Berg, Johannes; Roth, Siegfried

    2015-01-01

    Toll-dependent patterning of the dorsoventral axis in Drosophila represents one of the best understood gene regulatory networks. However, its evolutionary origin has remained elusive. Outside the insects Toll is not known for a patterning function, but rather for a role in pathogen defense. Here, we show that in the milkweed bug Oncopeltus fasciatus, whose lineage split from Drosophila's more than 350 million years ago, Toll is only required to polarize a dynamic BMP signaling network. A theoretical model reveals that this network has self-regulatory properties and that shallow Toll signaling gradients are sufficient to initiate axis formation. Such gradients can account for the experimentally observed twinning of insect embryos upon egg fragmentation and might have evolved from a state of uniform Toll activity associated with protecting insect eggs against pathogens. PMID:25962855

  14. The dynamics of signal amplification by macromolecular assemblies for the control of chromosome segregation

    PubMed Central

    Lee, Semin; Bolanos-Garcia, Victor M.

    2014-01-01

    The control of chromosome segregation relies on the spindle assembly checkpoint (SAC), a complex regulatory system that ensures the high fidelity of chromosome segregation in higher organisms by delaying the onset of anaphase until each chromosome is properly bi-oriented on the mitotic spindle. Central to this process is the establishment of multiple yet specific protein-protein interactions in a narrow time-space window. Here we discuss the highly dynamic nature of multi-protein complexes that control chromosome segregation in which an intricate network of weak but cooperative interactions modulate signal amplification to ensure a proper SAC response. We also discuss the current structural understanding of the communication between the SAC and the kinetochore; how transient interactions can regulate the assembly and disassembly of the SAC as well as the challenges and opportunities for the definition and the manipulation of the flow of information in SAC signaling. PMID:25324779

  15. Dynamic BMP signaling polarized by Toll patterns the dorsoventral axis in a hemimetabolous insect

    PubMed Central

    Sachs, Lena; Chen, Yen-Ta; Drechsler, Axel; Lynch, Jeremy A; Panfilio, Kristen A; Lässig, Michael; Berg, Johannes; Roth, Siegfried

    2015-01-01

    Toll-dependent patterning of the dorsoventral axis in Drosophila represents one of the best understood gene regulatory networks. However, its evolutionary origin has remained elusive. Outside the insects Toll is not known for a patterning function, but rather for a role in pathogen defense. Here, we show that in the milkweed bug Oncopeltus fasciatus, whose lineage split from Drosophila's more than 350 million years ago, Toll is only required to polarize a dynamic BMP signaling network. A theoretical model reveals that this network has self-regulatory properties and that shallow Toll signaling gradients are sufficient to initiate axis formation. Such gradients can account for the experimentally observed twinning of insect embryos upon egg fragmentation and might have evolved from a state of uniform Toll activity associated with protecting insect eggs against pathogens. DOI: http://dx.doi.org/10.7554/eLife.05502.001 PMID:25962855

  16. Reporting from the Field: Genetically Encoded Fluorescent Reporters Uncover Signaling Dynamics in Living Biological Systems

    PubMed Central

    Mehta, Sohum; Zhang, Jin

    2015-01-01

    Real-time visualization of a wide range of biochemical processes in living systems is being made possible through the development and application of genetically encoded fluorescent reporters. These versatile biosensors have proven themselves tailor-made to the study of signal transduction, and in this review, we discuss some of the unique insights that they continue to provide regarding the spatial organization and dynamic regulation of intracellular signaling networks. In addition, we explore the more recent push to expand the scope of biological phenomena that can be monitored using these reporters, while also considering the potential to integrate this highly adaptable technology with a number of emerging techniques that may significantly broaden our view of how networks of biochemical processes shape larger biological phenomena. PMID:21495849

  17. Dynamic control of type I IFN signalling by an integrated network of negative regulators.

    PubMed

    Porritt, Rebecca A; Hertzog, Paul J

    2015-03-01

    Whereas type I interferons (IFNs) have critical roles in protection from pathogens, excessive IFN responses contribute to pathology in both acute and chronic settings, pointing to the importance of balancing activating signals with regulatory mechanisms that appropriately tune the response. Here we review evidence for an integrated network of negative regulators of IFN production and action, which function at all levels of the activating and effector signalling pathways. We propose that the aim of this extensive network is to limit tissue damage while enabling an IFN response that is temporally appropriate and of sufficient magnitude. Understanding the architecture and dynamics of this network, and how it differs in distinct tissues, will provide new insights into IFN biology and aid the design of more effective therapeutics. PMID:25725583

  18. Signal conditioning of single-active-arm strain gages used for dynamic stress measurement

    NASA Astrophysics Data System (ADS)

    Mahrenholz, B. G.

    1991-09-01

    A new strain-gage signal conditioner is described for use in the measurement of dynamic stresses on turbine engine compressor blades. This conditioner has two novel circuits. A new gage excitation circuit corrects for changes in lead-wire resistance by automatically adjusting resistances in series with the leads to the gage. This maintains a balanced configuration that offers better high-frequency common-mode rejection and less broadband noise than with constant-current excitation. Another circuit in the conditioner provides system calibration by shunting a small value resistor that is in series with the gage to produce resistance change that accurately simulates the gage resistance change. The shunting is done at a rate of 1,000 times a second to produce a 1-kHz square-wave calibration signal. The calibration circuit may be used to check on the integrity of the gage and its cabling.

  19. Resolving dynamics of cell signaling via real-time imaging of the immunological synapse.

    SciTech Connect

    Stevens, Mark A.; Pfeiffer, Janet R.; Wilson, Bridget S.; Timlin, Jerilyn Ann; Thomas, James L.; Lidke, Keith A.; Spendier, Kathrin; Oliver, Janet M.; Carroll-Portillo, Amanda; Aaron, Jesse S.; Mirijanian, Dina T.; Carson, Bryan D.; Burns, Alan Richard; Rebeil, Roberto

    2009-10-01

    This highly interdisciplinary team has developed dual-color, total internal reflection microscopy (TIRF-M) methods that enable us to optically detect and track in real time protein migration and clustering at membrane interfaces. By coupling TIRF-M with advanced analysis techniques (image correlation spectroscopy, single particle tracking) we have captured subtle changes in membrane organization that characterize immune responses. We have used this approach to elucidate the initial stages of cell activation in the IgE signaling network of mast cells and the Toll-like receptor (TLR-4) response in macrophages stimulated by bacteria. To help interpret these measurements, we have undertaken a computational modeling effort to connect the protein motion and lipid interactions. This work provides a deeper understanding of the initial stages of cellular response to external agents, including dynamics of interaction of key components in the signaling network at the 'immunological synapse,' the contact region of the cell and its adversary.

  20. Aurora A drives early signalling and vesicle dynamics during T-cell activation.

    PubMed

    Blas-Rus, Noelia; Bustos-Morán, Eugenio; Pérez de Castro, Ignacio; de Cárcer, Guillermo; Borroto, Aldo; Camafeita, Emilio; Jorge, Inmaculada; Vázquez, Jesús; Alarcón, Balbino; Malumbres, Marcos; Martín-Cófreces, Noa B; Sánchez-Madrid, Francisco

    2016-01-01

    Aurora A is a serine/threonine kinase that contributes to the progression of mitosis by inducing microtubule nucleation. Here we have identified an unexpected role for Aurora A kinase in antigen-driven T-cell activation. We find that Aurora A is phosphorylated at the immunological synapse (IS) during TCR-driven cell contact. Inhibition of Aurora A with pharmacological agents or genetic deletion in human or mouse T cells severely disrupts the dynamics of microtubules and CD3ζ-bearing vesicles at the IS. The absence of Aurora A activity also impairs the activation of early signalling molecules downstream of the TCR and the expression of IL-2, CD25 and CD69. Aurora A inhibition causes delocalized clustering of Lck at the IS and decreases phosphorylation levels of tyrosine kinase Lck, thus indicating Aurora A is required for maintaining Lck active. These findings implicate Aurora A in the propagation of the TCR activation signal. PMID:27091106

  1. Multiple Model-Informed Open-Loop Control of Uncertain Intracellular Signaling Dynamics

    PubMed Central

    Perley, Jeffrey P.; Mikolajczak, Judith; Harrison, Marietta L.; Buzzard, Gregery T.; Rundell, Ann E.

    2014-01-01

    Computational approaches to tune the activation of intracellular signal transduction pathways both predictably and selectively will enable researchers to explore and interrogate cell biology with unprecedented precision. Techniques to control complex nonlinear systems typically involve the application of control theory to a descriptive mathematical model. For cellular processes, however, measurement assays tend to be too time consuming for real-time feedback control and models offer rough approximations of the biological reality, thus limiting their utility when considered in isolation. We overcome these problems by combining nonlinear model predictive control with a novel adaptive weighting algorithm that blends predictions from multiple models to derive a compromise open-loop control sequence. The proposed strategy uses weight maps to inform the controller of the tendency for models to differ in their ability to accurately reproduce the system dynamics under different experimental perturbations (i.e. control inputs). These maps, which characterize the changing model likelihoods over the admissible control input space, are constructed using preexisting experimental data and used to produce a model-based open-loop control framework. In effect, the proposed method designs a sequence of control inputs that force the signaling dynamics along a predefined temporal response without measurement feedback while mitigating the effects of model uncertainty. We demonstrate this technique on the well-known Erk/MAPK signaling pathway in T cells. In silico assessment demonstrates that this approach successfully reduces target tracking error by 52% or better when compared with single model-based controllers and non-adaptive multiple model-based controllers. In vitro implementation of the proposed approach in Jurkat cells confirms a 63% reduction in tracking error when compared with the best of the single-model controllers. This study provides an experimentally

  2. Molecular Dynamics Investigation of a Mechanism of Allosteric Signal Transmission in Ribosomes.

    PubMed

    Makarov, G I; Golovin, A V; Sumbatyan, N V; Bogdanov, A A

    2015-08-01

    The ribosome is a molecular machine that synthesizes all cellular proteins via translation of genetic information encoded in polynucleotide chain of messenger RNA. Transition between different stages of the ribosome working cycle is strictly coordinated by changes in structure and mutual position both of subunits of the ribosome and its ligands. Therein, information regarding structural transformations is transmitted between functional centers of the ribosome through specific signals. Usually, functional centers of ribosomes are located at a distance reaching up to several tens of angstroms, and it is believed that such signals are transduced allosterically. In our study, we attempted to answer the question of how allosteric signal can be transmitted from one of the so-called sensory elements of ribosomal tunnel (RT) to the peptidyl transferase center (PTC). A segment of RT wall from the E. coli ribosome composed of nucleotide residues A2058, A2059, m(2)A2503, G2061, A2062, and C2063 of its 23S rRNA was examined by molecular dynamics simulations. It was found that a potential signal transduction pathway A2058-C2063 acted as a dynamic ensemble of interdependent conformational states, wherein cascade-like changes can occur. It was assumed that structural rearrangement in the A2058-C2063 RT segment results in reversible inactivation of PTC due to a strong stacking contact between functionally important U2585 residue of the PTC and nucleotide residue C2063. A potential role for the observed conformational transition in the A2058-C2063 segment for regulating ribosome activity is discussed. PMID:26547073

  3. Multiple model-informed open-loop control of uncertain intracellular signaling dynamics.

    PubMed

    Perley, Jeffrey P; Mikolajczak, Judith; Harrison, Marietta L; Buzzard, Gregery T; Rundell, Ann E

    2014-04-01

    Computational approaches to tune the activation of intracellular signal transduction pathways both predictably and selectively will enable researchers to explore and interrogate cell biology with unprecedented precision. Techniques to control complex nonlinear systems typically involve the application of control theory to a descriptive mathematical model. For cellular processes, however, measurement assays tend to be too time consuming for real-time feedback control and models offer rough approximations of the biological reality, thus limiting their utility when considered in isolation. We overcome these problems by combining nonlinear model predictive control with a novel adaptive weighting algorithm that blends predictions from multiple models to derive a compromise open-loop control sequence. The proposed strategy uses weight maps to inform the controller of the tendency for models to differ in their ability to accurately reproduce the system dynamics under different experimental perturbations (i.e. control inputs). These maps, which characterize the changing model likelihoods over the admissible control input space, are constructed using preexisting experimental data and used to produce a model-based open-loop control framework. In effect, the proposed method designs a sequence of control inputs that force the signaling dynamics along a predefined temporal response without measurement feedback while mitigating the effects of model uncertainty. We demonstrate this technique on the well-known Erk/MAPK signaling pathway in T cells. In silico assessment demonstrates that this approach successfully reduces target tracking error by 52% or better when compared with single model-based controllers and non-adaptive multiple model-based controllers. In vitro implementation of the proposed approach in Jurkat cells confirms a 63% reduction in tracking error when compared with the best of the single-model controllers. This study provides an experimentally

  4. Effect of Nasal Obstruction on Continuous Positive Airway Pressure Treatment: Computational Fluid Dynamics Analyses

    PubMed Central

    Wakayama, Tadashi; Suzuki, Masaaki; Tanuma, Tadashi

    2016-01-01

    Objective Nasal obstruction is a common problem in continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea and limits treatment compliance. The purpose of this study is to model the effects of nasal obstruction on airflow parameters under CPAP using computational fluid dynamics (CFD), and to clarify quantitatively the relation between airflow velocity and pressure loss coefficient in subjects with and without nasal obstruction. Methods We conducted an observational cross-sectional study of 16 Japanese adult subjects, of whom 9 had nasal obstruction and 7 did not (control group). Three-dimensional reconstructed models of the nasal cavity and nasopharynx with a CPAP mask fitted to the nostrils were created from each subject’s CT scans. The digital models were meshed with tetrahedral cells and stereolithography formats were created. CPAP airflow simulations were conducted using CFD software. Airflow streamlines and velocity contours in the nasal cavities and nasopharynx were compared between groups. Simulation models were confirmed to agree with actual measurements of nasal flow rate and with pressure and flow rate in the CPAP machine. Results Under 10 cmH2O CPAP, average maximum airflow velocity during inspiration was 17.6 ± 5.6 m/s in the nasal obstruction group but only 11.8 ± 1.4 m/s in the control group. The average pressure drop in the nasopharynx relative to inlet static pressure was 2.44 ± 1.41 cmH2O in the nasal obstruction group but only 1.17 ± 0.29 cmH2O in the control group. The nasal obstruction and control groups were clearly separated by a velocity threshold of 13.5 m/s, and pressure loss coefficient threshold of approximately 10.0. In contrast, there was no significant difference in expiratory pressure in the nasopharynx between the groups. Conclusion This is the first CFD analysis of the effect of nasal obstruction on CPAP treatment. A strong correlation between the inspiratory pressure loss coefficient and maximum airflow

  5. Functional Consequences of Perturbed CXCL12 Signal Processing: Analyses of Immature Hematopoiesis in GRK6-Deficient Mice

    PubMed Central

    Chudziak, Doreen; Spohn, Gabriele; Karpova, Darja; Dauber, Katrin; Wiercinska, Eliza; Miettinen, Johanna A.; Papayannopoulou, Thalia

    2015-01-01

    Hematopoietic stem and progenitor cells (HSPCs) reside in bone marrow (BM) in an environment rich in CXCL12, the ligand for CXCR4, which is constitutively expressed on all immature hematopoietic cells in BM. This ligand-receptor pair critically controls HSPC retention and (relative) quiescence in BM. Interestingly, in a chemokine-abundant environment, CXCR4 surface expression and CXCL12 sensitivity of BM-residing HSPCs are continuously maintained. The mechanisms underlying this peculiar pattern of G-protein signal integration by BM-HSPCs are unknown. G-protein receptor kinases (GRKs) control receptor function by phosphorylating the intracellular domains upon ligand-induced activation, which results in receptor internalization and transient refractoriness. Using, therefore, a GRK6-deficient (GRK6−/−) mouse, we sought to address how perturbed ligand-induced CXCR4 (in)activation affects HSPC behavior in vitro and in vivo. In vitro, GRK6−/− HSPCs were characterized by hyper-responsiveness to CXCL12, as expected. In vivo, GRK6−/− immature hematopoiesis was characterized by a marked expansion of immature hematopoiesis in spleens and a modest repopulation defect in serial competitive transplantation. Enforced mobilization with granulocyte colony-stimulating factor (G-CSF) and AMD3100 was normal, as was hematopoietic regeneration after noncompetitive transplantation or pharmacological myelosuppression. These observations illustrate that GRK-mediated restriction of CXCR4 signal input after ligand engagement is largely dispensable for BM-resident HSPCs, which may explain how continuous CXCL12 responsiveness of BM-HSPCs can be maintained. PMID:25316534

  6. Novel optical-based methods and analyses for elucidating cellular mechanics and dynamics

    NASA Astrophysics Data System (ADS)

    Koo, Peter K.

    Resolving distinct biochemical interaction states by analyzing the diffusive behaviors of individual protein trajectories is challenging due to the limited statistics provided by short trajectories and experimental noise sources, which are intimately coupled into each proteins localization. In the first part of this thesis, we introduce a novel, a machine-learning based classification methodology, called perturbation expectation-maximization (pEM), which simultaneously analyzes a population of protein trajectories to uncover the system of short-time diffusive behaviors which collectively result from distinct biochemical interactions. We then discuss an experimental application of pEM to Rho GTPase, an integral regulator of cytoskeletal dynamics and cellular homeostasis, inside live cells. We also derive the maximum likelihood estimator (MLE) for driven diffusion, confined diffusion, and fractional Brownian motion. We demonstrate that MLE yields improved estimates in comparison with traditional diffusion analysis, namely mean squared displacement analysis. In addition, we also introduce mleBayes, which is an empirical Bayesian model selection scheme to classify an individual protein trajectory to a given diffusion mode. By employing mleBayes on simulated data, we demonstrate that accurate determination of the underlying diffusive properties, beyond normal diffusion, remains challenging when analyzing particle trajectories on an individual basis. To improve upon the statistical limitations of classification from analyzing trajectories on an individual basis, we extend pEM with a new version (pEMv2) to simultaneously analyzing a collection of particle trajectories to uncover the system of interactions which give rise to unique normal or non-normal diffusive states. We test the performance of pEMv2 on various sets of simulated particle trajectories which transition between various modes of normal and non-normal diffusive states to highlight considerations when

  7. A new measurement method for the dynamic resistance signal during the resistance spot welding process

    NASA Astrophysics Data System (ADS)

    Wang, Lijing; Hou, Yanyan; Zhang, Hongjie; Zhao, Jian; Xi, Tao; Qi, Xiangyang; Li, Yafeng

    2016-09-01

    To measure the dynamic resistance signal during the resistance spot welding process, some original work was carried out and a new measurement method was developed. Compared with the traditional method, using the instantaneous electrode voltage and welding current at peak current point in each half cycle, the resistance curve from the newly proposed method can provide more details of the dynamic resistance changes over time. To test the specific performance of the proposed method, a series of welding experiments were carried out and the tensile shear strengths of the weld samples were measured. Then, the measurement error of the proposed method was evaluated. Several features were extracted from the dynamic resistance curves. The correlations between the extracted features and weld strength were analyzed and the results show that these features are closely related to the weld strength and they can be used for welding quality monitoring. Moreover, the dynamic resistance curve from the newly proposed method can also be used to monitor some abnormal welding conditions.

  8. Noise-driven signal transmission device using molecular dynamics of organic polymers

    NASA Astrophysics Data System (ADS)

    Asakawa, Naoki; Umemura, Koichiro; Fujise, Shinya; Yazawa, Koji; Shimizu, Tadashi; Tansho, Masataka; Kanki, Teruo; Tanaka, Hidekazu

    2014-01-01

    Stochastic threshold devices using a trap-filling transition (TFT) coupled with molecular dynamics in poly(3-alkylthiophene)s were fabricated as potential key devices for noise-driven bioinspired sensors and information processors. This article deals with variable-temperature direct current conductivity and alternating current impedance measurements for vertical-type device elements of Au/regioregular poly(3-decylthiophene) ((RR-P3DT) (thickness: 100 nm)/Au, which show multiple conducting states and quasi-stochastic transitions between these states. Noise measurements indicate the ω-2-type (if VVTFT) power spectral densities, where V and VTFT are an applied voltage and the voltage for TFT, respectively. The noise generation is due to the TFT associated with twist dynamics of π-conjugated polymers near the order-disorder phase transition (ODT). At 298 K, the quasi-stochastic behavior is more noticeable for RR-P3DT than poly(3-hexylthiophene). The quasi-stochastic property is employed to a stochastic one-directional signal transmitting device using optical-electric conversion. The dynamics of ODT for powder samples were also investigated by differential scanning calorimetry measurements and high-resolution solid-state C13 nuclear magnetic resonance spectroscopy, and the correlation of the molecular structure and dynamics with electric properties was discussed.

  9. Profiling the Dynamics of a Human Phosphorylome Reveals New Components in HGF/c-Met Signaling

    PubMed Central

    Wan, Jun; Xia, Shuli; Newman, Robert; Hu, Jianfei; Zhang, Jin; Hayward, S. Diane; Qian, Jiang; Laterra, John; Zhu, Heng

    2013-01-01

    Protein phosphorylation is a dynamic and reversible event that greatly influences cellular function. Identifying the key regulatory elements that determine cellular phenotypes during development and oncogenesis requires the ability to dynamically monitor proteome-wide events. Here, we report the development of a new strategy to monitor dynamic changes of protein phosphorylation in cells and tissues using functional protein microarrays as the readout. To demonstrate this technology's ability to identify condition-dependent phosphorylation events, human protein microarrays were incubated with lysates from cells or tissues under activation or inhibition of c-Met, a receptor tyrosine kinase involved in tissue morphogenesis and malignancy. By comparing the differences between the protein phosphorylation profiles obtained using the protein microarrays, we were able to recover many of the proteins that are known to be specifically activated (i.e., phosphorylated) upon c-Met activation by the hepatocyte growth factor (HGF). Most importantly, we discovered many proteins that were differentially phosphorylated by lysates from cells or tissues when the c-Met pathway was active. Using phosphorylation-specific antibodies, we were able to validate several candidate proteins as new downstream components of the c-Met signaling pathway in cells. We envision that this new approach, like its DNA microarray counterpart, can be further extended toward profiling dynamics of global protein phosphorylation under many different physiological conditions both in cellulo and in vivo in a high-throughput and cost-effective fashion. PMID:24023761

  10. Modest Interference with Actin Dynamics in Primary T Cell Activation by Antigen Presenting Cells Preferentially Affects Lamellal Signaling

    PubMed Central

    Roybal, Kole T.; Mace, Emily M.; Clark, Danielle J.; Leard, Alan D.; Herman, Andrew; Verkade, Paul; Orange, Jordan S.; Wülfing, Christoph

    2015-01-01

    Dynamic subcellular distributions of signaling system components are critical regulators of cellular signal transduction through their control of molecular interactions. Understanding how signaling activity depends on such distributions and the cellular structures driving them is required for comprehensive insight into signal transduction. In the activation of primary murine T cells by antigen presenting cells (APC) signaling intermediates associate with various subcellular structures, prominently a transient, wide, and actin-associated lamellum extending from an interdigitated T cell:APC interface several micrometers into the T cell. While actin dynamics are well established as general regulators of cellular organization, their role in controlling signaling organization in primary T cell:APC couples and the specific cellular structures driving it is unresolved. Using modest interference with actin dynamics with a low concentration of Jasplakinolide as corroborated by costimulation blockade we show that T cell actin preferentially controls lamellal signaling localization and activity leading downstream to calcium signaling. Lamellal localization repeatedly related to efficient T cell function. This suggests that the transient lamellal actin matrix regulates T cell signaling associations that facilitate T cell activation. PMID:26237588

  11. Integrative Analyses of Uterine Transcriptome and MicroRNAome Reveal Compromised LIF-STAT3 Signaling and Progesterone Response in the Endometrium of Patients with Recurrent/Repeated Implantation Failure (RIF)

    PubMed Central

    Lim, Eun Jin; Park, Miseon; Yoon, Jung Ah; Kim, Yeon Sun; Kim, Eun-Kyung; Shin, Ji-Eun; Kim, Ji Hyang; Kwon, Hwang; Song, Haengseok; Choi, Dong-Hee

    2016-01-01

    Intimate two-way interactions between the implantation-competent blastocyst and receptive uterus are prerequisite for successful embryo implantation. In humans, recurrent/repeated implantation failure (RIF) may occur due to altered uterine receptivity with aberrant gene expression in the endometrium as well as genetic defects in embryos. Several studies have been performed to understand dynamic changes of uterine transcriptome during menstrual cycles in humans. However, uterine transcriptome of the patients with RIF has not been clearly investigated yet. Here we show that several signaling pathways as well as many genes and microRNAs are dysregulated in the endometrium of patients with RIF (RIFE). Whereas unsupervised hierarchical clustering showed that overall mRNA and microRNA profiles of RIFE were similar to those of endometria of healthy women, many genes were significantly dysregulated in RIFE (cut off at 1.5 fold change). The majority (~75%) of differentially expressed genes in RIFE including S100 calcium binding protein P (S100P), Chemokine (C-X-C motif) ligand 13 (CXCL13) and SIX homeobox 1 (SIX1) were down-regulated, suggesting that reduced uterine expression of these genes is associated with RIF. Gene Set Enrichment analyses (GSEA) for mRNA microarrays revealed that various signaling pathways including Leukemia inhibitory factor (LIF) signaling and a P4 response were dysregulated in RIFE although expression levels of Estrogen receptor α (ERα) and Progesterone receptor (PR) were not significantly altered in RIFE. Furthermore, expression and phosphorylation of Signal transducer and activator of transcription 3 (STAT3) are reduced and a gene set associated with Janus kinase (JAK)-STAT signaling pathway is systemically down-regulated in these patients. Pairwise analyses of microRNA arrays with prediction of dysregulated microRNAs based on mRNA expression datasets demonstrated that 6 microRNAs are aberrantly regulated in RIFE. Collectively, we here suggest

  12. Comparison of Dynamical Behaviors Between Monofunctional and Bifunctional Two-Component Signaling Modules

    NASA Astrophysics Data System (ADS)

    Yang, Xiyan; Wu, Yahao; Yuan, Zhanjiang

    2015-06-01

    Two-component signaling modules exist extensively in bacteria and microbes. These modules can be, based on their distinct network structures, divided into two types: the monofunctional system (denoted by MFS) where the sensor kinase (SK) modulates only phosphorylation of the response regulator (RR), and the bifunctional system (denoted by BFS) where the SK catalyzes both phosphorylation and dephosphorylation of the RR. Here, we analyze dynamical behaviors of these two systems based on stability theory, focusing on differences between them. The analysis of the deterministic behavior indicates that there is no difference between the two modules, that is, each system has the unique stable steady state. However, there are significant differences in stochastic behavior between them. Specifically, if the mean phosphorylated SK level is kept the same for the two modules, then the variance and the Fano factor for the phosphorylated RR in the BFS are always no less than those in the MFS, indicating that bifunctionality always enhances fluctuations. The correlation between the phosphorylated SK and the phosphorylated RR in the BFS is always positive mainly due to competition between system components, but this correlation in the MFS may be positive, almost zero, or negative, depending on the ratio between two rate constants. Our overall analysis indicates that differences between dynamical behaviors of monofunctional and bifunctional signaling modules are mainly in the stochastic rather than deterministic aspect.

  13. Glycerol Monolaurate (GML) inhibits human T cell signaling and function by disrupting lipid dynamics

    PubMed Central

    Zhang, Michael S.; Sandouk, Aline; Houtman, Jon C. D.

    2016-01-01

    Glycerol Monolaurate (GML) is a naturally occurring fatty acid widely utilized in food, cosmetics, and homeopathic supplements. GML is a potent antimicrobial agent that targets a range of bacteria, fungi, and enveloped viruses but select findings suggest that GML also has immunomodulatory functions. In this study, we have mechanistically examined if GML affects the signaling and functional output of human primary T cells. We found that GML potently altered order and disorder dynamics in the plasma membrane that resulted in reduced formation of LAT, PLC-γ, and AKT microclusters. Altered membrane events induced selective inhibition of TCR-induced phosphorylation of regulatory P85 subunit of PI3K and AKT as well as abrogated calcium influx. Ultimately, GML treatment potently reduced TCR-induced production of IL-2, IFN-γ, TNF-α, and IL-10. Our data reveal that the widely used anti-microbial agent GML also alters the lipid dynamics of human T cells, leading to their defective signaling and function. PMID:27456316

  14. Glycerol Monolaurate (GML) inhibits human T cell signaling and function by disrupting lipid dynamics.

    PubMed

    Zhang, Michael S; Sandouk, Aline; Houtman, Jon C D

    2016-01-01

    Glycerol Monolaurate (GML) is a naturally occurring fatty acid widely utilized in food, cosmetics, and homeopathic supplements. GML is a potent antimicrobial agent that targets a range of bacteria, fungi, and enveloped viruses but select findings suggest that GML also has immunomodulatory functions. In this study, we have mechanistically examined if GML affects the signaling and functional output of human primary T cells. We found that GML potently altered order and disorder dynamics in the plasma membrane that resulted in reduced formation of LAT, PLC-γ, and AKT microclusters. Altered membrane events induced selective inhibition of TCR-induced phosphorylation of regulatory P85 subunit of PI3K and AKT as well as abrogated calcium influx. Ultimately, GML treatment potently reduced TCR-induced production of IL-2, IFN-γ, TNF-α, and IL-10. Our data reveal that the widely used anti-microbial agent GML also alters the lipid dynamics of human T cells, leading to their defective signaling and function. PMID:27456316

  15. Scale-Free and Multifractal Time Dynamics of fMRI Signals during Rest and Task

    PubMed Central

    Ciuciu, P.; Varoquaux, G.; Abry, P.; Sadaghiani, S.; Kleinschmidt, A.

    2012-01-01

    Scaling temporal dynamics in functional MRI (fMRI) signals have been evidenced for a decade as intrinsic characteristics of ongoing brain activity (Zarahn et al., 1997). Recently, scaling properties were shown to fluctuate across brain networks and to be modulated between rest and task (He, 2011): notably, Hurst exponent, quantifying long memory, decreases under task in activating and deactivating brain regions. In most cases, such results were obtained: First, from univariate (voxelwise or regionwise) analysis, hence focusing on specific cognitive systems such as Resting-State Networks (RSNs) and raising the issue of the specificity of this scale-free dynamics modulation in RSNs. Second, using analysis tools designed to measure a single scaling exponent related to the second order statistics of the data, thus relying on models that either implicitly or explicitly assume Gaussianity and (asymptotic) self-similarity, while fMRI signals may significantly depart from those either of those two assumptions (Ciuciu et al., 2008; Wink et al., 2008). To address these issues, the present contribution elaborates on the analysis of the scaling properties of fMRI temporal dynamics by proposing two significant variations. First, scaling properties are technically investigated using the recently introduced Wavelet Leader-based Multifractal formalism (WLMF; Wendt et al., 2007). This measures a collection of scaling exponents, thus enables a richer and more versatile description of scale invariance (beyond correlation and Gaussianity), referred to as multifractality. Also, it benefits from improved estimation performance compared to tools previously used in the literature. Second, scaling properties are investigated in both RSN and non-RSN structures (e.g., artifacts), at a broader spatial scale than the voxel one, using a multivariate approach, namely the Multi-Subject Dictionary Learning (MSDL) algorithm (Varoquaux et al., 2011) that produces a set of spatial components that

  16. Structural insights into the dynamic process of β2-adrenergic receptor signaling

    PubMed Central

    Manglik, Aashish; Kim, Tae Hun; Masureel, Matthieu; Altenbach, Christian; Yang, Zhongyu; Hilger, Daniel; Lerch, Michael T.; Kobilka, Tong Sun; Thian, Foon Sun; Hubbell, Wayne L.; Prosser, R. Scott; Kobilka, Brian K.

    2015-01-01

    SUMMARY G protein-coupled receptors (GPCRs) transduce signals from the extracellular environment to intracellular proteins. To gain structural insight into the regulation of receptor cytoplasmic conformations by extracellular ligands during signaling, we examine the structural dynamics of the cytoplasmic domain of the β2-adrenergic receptor (β2AR) using 19F-fluorine NMR and double electron-electron resonance spectroscopy. These studies show that unliganded and inverse-agonist-bound β2AR exists predominantly in two inactive conformations that exchange within hundreds of microseconds. Although agonists shift the equilibrium towards a conformation capable of engaging cytoplasmic G proteins, they do so incompletely, resulting in increased conformational heterogeneity and the coexistence of inactive, intermediate and active states. Complete transition to the active conformation requires subsequent interaction with a G-protein or an intracellular G protein mimetic. These studies demonstrate a loose allosteric coupling of the agonist-binding site and G protein-coupling interface that may generally be responsible for the complex signaling behavior observed for many GPCRs. PMID:25981665

  17. Estimating and improving the signal-to-noise ratio of time series by symbolic dynamics.

    PubMed

    Graben, P

    2001-11-01

    We investigate the effect of symbolic encoding applied to times series consisting of some deterministic signal and additive noise, as well as time series given by a deterministic signal with randomly distributed initial conditions as a model of event-related brain potentials. We introduce an estimator of the signal-to-noise ratio (SNR) of the system by means of time averages of running complexity measures such as Shannon and Rényi entropies, and prove its asymptotical equivalence with the linear SNR in the case of Shannon entropies of symbol distributions. A SNR improvement factor is defined, exhibiting a maximum for intermediate values of noise amplitude in analogy to stochastic resonance phenomena. We demonstrate that the maximum of the SNR improvement factor can be shifted toward smaller noise amplitudes by using higher order Rényi entropies instead of the Shannon entropy. For a further improvement of the SNR, a half wave encoding of noisy time series is introduced. Finally, we discuss the effect of noisy phases on the linear SNR as well as on the SNR defined by symbolic dynamics. It is shown that longer symbol sequences yield an improvement of the latter. PMID:11735897

  18. Balanced ionotropic receptor dynamics support signal estimation via voltage-dependent membrane noise.

    PubMed

    Marcoux, Curtis M; Clarke, Stephen E; Nesse, William H; Longtin, Andre; Maler, Leonard

    2016-01-01

    Encoding behaviorally relevant stimuli in a noisy background is critical for animals to survive in their natural environment. We identify core biophysical and synaptic mechanisms that permit the encoding of low-frequency signals in pyramidal neurons of the weakly electric fish Apteronotus leptorhynchus, an animal that can accurately encode even miniscule amplitude modulations of its self-generated electric field. We demonstrate that slow NMDA receptor (NMDA-R)-mediated excitatory postsynaptic potentials (EPSPs) are able to summate over many interspike intervals (ISIs) of the primary electrosensory afferents (EAs), effectively eliminating the baseline EA ISI correlations from the pyramidal cell input. Together with a dynamic balance of NMDA-R and GABA-A-R currents, this permits stimulus-evoked changes in EA spiking to be transmitted efficiently to target electrosensory lobe (ELL) pyramidal cells, for encoding low-frequency signals. Interestingly, AMPA-R activity is depressed and appears to play a negligible role in the generation of action potentials. Instead, we hypothesize that cell-intrinsic voltage-dependent membrane noise supports the encoding of perithreshold sensory input; this noise drives a significant proportion of pyramidal cell spikes. Together, these mechanisms may be sufficient for the ELL to encode signals near the threshold of behavioral detection. PMID:26561607

  19. Analysis and compensation for code Doppler effect of BDS II signal under high dynamics

    NASA Astrophysics Data System (ADS)

    Ouyang, Xiaofeng; Zeng, Fangling

    2016-01-01

    In high dynamic circumstances, the acquisition of BDS (BeiDou Navigation Satellite System) signal would be affected by the pseudo-code Doppler. The pseudo-code frequency shift is more prominent and complex when BOC modulation has been adopted by BDS-II, but is not yet involved in current compensation algorithm. In addition, the most frequently used code Doppler compensation algorithm is modifying the sampling rate or local bit rate, which not only increases the complexity of the acquisition and tracking, but also is barely realizable for the hardware receiver to modify the local frequency. Therefore, this paper proposes a code Doppler compensation method based on double estimator receiver, which simultaneously controls NCO delay of code tracking loop and subcarrier tracking loop to compensate for pseudo-code frequency shift. The simulation and test are implemented with BDS-II BOC signal. The test results demonstrate that the proposed algorithm can effectively compensate for pseudo-code Doppler of BOC signal and has detection probability 3dB higher than the uncompensated situation when the false alarm rate is under 0.01 and the coherent integration time is 1ms.

  20. Reliable emotion recognition system based on dynamic adaptive fusion of forehead biopotentials and physiological signals.

    PubMed

    Khezri, Mahdi; Firoozabadi, Mohammad; Sharafat, Ahmad Reza

    2015-11-01

    In this study, we proposed a new adaptive method for fusing multiple emotional modalities to improve the performance of the emotion recognition system. Three-channel forehead biosignals along with peripheral physiological measurements (blood volume pressure, skin conductance, and interbeat intervals) were utilized as emotional modalities. Six basic emotions, i.e., anger, sadness, fear, disgust, happiness, and surprise were elicited by displaying preselected video clips for each of the 25 participants in the experiment; the physiological signals were collected simultaneously. In our multimodal emotion recognition system, recorded signals with the formation of several classification units identified the emotions independently. Then the results were fused using the adaptive weighted linear model to produce the final result. Each classification unit is assigned a weight that is determined dynamically by considering the performance of the units during the testing phase and the training phase results. This dynamic weighting scheme enables the emotion recognition system to adapt itself to each new user. The results showed that the suggested method outperformed conventional fusion of the features and classification units using the majority voting method. In addition, a considerable improvement, compared to the systems that used the static weighting schemes for fusing classification units, was also shown. Using support vector machine (SVM) and k-nearest neighbors (KNN) classifiers, the overall classification accuracies of 84.7% and 80% were obtained in identifying the emotions, respectively. In addition, applying the forehead or physiological signals in the proposed scheme indicates that designing a reliable emotion recognition system is feasible without the need for additional emotional modalities. PMID:26253158

  1. Static and dynamic analyses on the MFTF (Mirror Fusion Test Facility)-B Axicell Vacuum Vessel System: Final report

    SciTech Connect

    Ng, D.S.

    1986-09-01

    The Mirror Fusion Test Facility (MFTF-B) at Lawrence Livermore National Laboratory (LLNL) is a large-scale, tandem-mirror-fusion experiment. MFTF-B comprises many highly interconnected systems, including a magnet array and a vacuum vessel. The vessel, which houses the magnet array, is supported by reinforced concrete piers and steel frames resting on an array of foundations and surrounded by a 7-ft-thick concrete shielding vault. The Pittsburgh-Des Moines (PDM) Corporation, which was awarded the contract to design and construct the vessel, carried out fixed-base static and dynamic analyses of a finite-element model of the axicell vessel and magnet systems, including the simulation of various loading conditions and three postulated earthquake excitations. Meanwhile, LLNL monitored PDM's analyses with modeling studies of its own, and independently evaluated the structural responses of the vessel in order to define design criteria for the interface members and other project equipment. The assumptions underlying the finite-element model and the behavior of the axicell vessel are described in detail in this report, with particular emphasis placed on comparing the LLNL and PDM studies and on analyzing the fixed-base behavior with the soil-structure interaction, which occurs between the vessel and the massive concrete vault wall during a postulated seismic event. The structural members that proved sensitive to the soil effect are also reevaluated.

  2. Inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells.

    PubMed

    Wang, Jiarui; Zhang, Xuemei; Ma, Danjun; Lee, Wai-Nang Paul; Xiao, Jing; Zhao, Yingchun; Go, Vay Liang; Wang, Qi; Yen, Yun; Recker, Robert; Xiao, Gary Guishan

    2013-01-01

    Oxythiamine (OT), an analogue of anti-metabolite, can suppress the nonoxidative synthesis of ribose and induce cell apoptosis by causing a G1 phase arrest in vitro and in vivo. However, the molecular mechanism remains unclear yet. In the present study, a quantitative proteomic analysis using the modified SILAC method (mSILAC) was performed to determine the effect of metabolic inhibition on dynamic changes of protein expression in MIA PaCa-2 cancer cells treated with OT at various doses (0 μM, 5 μM, 50 μM and 500 μM) and time points (0 h, 12 h and 48 h). A total of 52 differential proteins in MIA PaCa-2 cells treated with OT were identified, including 14 phosphorylated proteins. Based on the dynamic expression pattern, these proteins were categorized in three clusters, straight down-regulation (cluster 1, 37% of total proteins), upright "V" shape expression pattern (cluster 2, 47.8% total), and downright "V" shape pattern (cluster 3, 15.2% total). Among them, Annexin A1 expression was significantly down-regulated by OT treatment in time-dependent manner, while no change of this protein was observed in OT dose-dependent fashion. Pathway analysis suggested that inhibition of transketolase resulted in changes of multiple cellular signaling pathways associated with cell apoptosis. The temporal expression patterns of proteins revealed that OT altered dynamics of protein expression in time-dependent fashion by suppressing phosphor kinase expression, resulting in cancer cell apoptosis. Results from this study suggest that interference of single metabolic enzyme activity altered multiple cellular signaling pathways. PMID:23890079

  3. Beech Fructification and Bank Vole Population Dynamics - Combined Analyses of Promoters of Human Puumala Virus Infections in Germany

    PubMed Central

    Reil, Daniela; Imholt, Christian; Eccard, Jana Anja; Jacob, Jens

    2015-01-01

    The transmission of wildlife zoonoses to humans depends, amongst others, on complex interactions of host population ecology and pathogen dynamics within host populations. In Europe, the Puumala virus (PUUV) causes nephropathia epidemica in humans. In this study we investigated complex interrelations within the epidemic system of PUUV and its rodent host, the bank vole (Myodes glareolus). We suggest that beech fructification and bank vole abundance are both decisive factors affecting human PUUV infections. While rodent host dynamics are expected to be directly linked to human PUUV infections, beech fructification is a rather indirect predictor by serving as food source for PUUV rodent hosts. Furthermore, we examined the dependence of bank vole abundance on beech fructification. We analysed a 12-year (2001-2012) time series of the parameters: beech fructification (as food resource for the PUUV host), bank vole abundance and human incidences from 7 Federal States of Germany. For the first time, we could show the direct interrelation between these three parameters involved in human PUUV epidemics and we were able to demonstrate on a large scale that human PUUV infections are highly correlated with bank vole abundance in the present year, as well as beech fructification in the previous year. By using beech fructification and bank vole abundance as predictors in one model we significantly improved the degree of explanation of human PUUV incidence. Federal State was included as random factor because human PUUV incidence varies considerably among states. Surprisingly, the effect of rodent abundance on human PUUV infections is less strong compared to the indirect effect of beech fructification. Our findings are useful to facilitate the development of predictive models for host population dynamics and the related PUUV infection risk for humans and can be used for plant protection and human health protection purposes. PMID:26214509

  4. Spatial dynamics of action potentials estimated by dendritic Ca(2+) signals in insect projection neurons.

    PubMed

    Ogawa, Hiroto; Mitani, Ruriko

    2015-11-13

    The spatial dynamics of action potentials, including their propagation and the location of spike initiation zone (SIZ), are crucial for the computation of a single neuron. Compared with mammalian central neurons, the spike dynamics of invertebrate neurons remain relatively unknown. Thus, we examined the spike dynamics based on single spike-induced Ca(2+) signals in the dendrites of cricket mechanosensory projection neurons, known as giant interneurons (GIs). The Ca(2+) transients induced by a synaptically evoked single spike were larger than those induced by an antidromic spike, whereas subthreshold synaptic potentials caused no elevation of Ca(2+). These results indicate that synaptic activity enhances the dendritic Ca(2+) influx through voltage-gated Ca(2+) channels. Stimulation of the presynaptic sensory afferents ipsilateral to the recording site evoked a dendritic spike with higher amplitude than contralateral stimulation, thereby suggesting that alteration of the spike waveform resulted in synaptic enhancement of the dendritic Ca(2+) transients. The SIZ estimated from the spatial distribution of the difference in the Ca(2+) amplitude was distributed throughout the right and left dendritic branches across the primary neurite connecting them in GIs. PMID:26456645

  5. Advances in global sensitivity analyses of demographic-based species distribution models to address uncertainties in dynamic landscapes

    PubMed Central

    Curtis, Janelle M.R.

    2016-01-01

    Developing a rigorous understanding of multiple global threats to species persistence requires the use of integrated modeling methods that capture processes which influence species distributions. Species distribution models (SDMs) coupled with population dynamics models can incorporate relationships between changing environments and demographics and are increasingly used to quantify relative extinction risks associated with climate and land-use changes. Despite their appeal, uncertainties associated with complex models can undermine their usefulness for advancing predictive ecology and informing conservation management decisions. We developed a computationally-efficient and freely available tool (GRIP 2.0) that implements and automates a global sensitivity analysis of coupled SDM-population dynamics models for comparing the relative influence of demographic parameters and habitat attributes on predicted extinction risk. Advances over previous global sensitivity analyses include the ability to vary habitat suitability across gradients, as well as habitat amount and configuration of spatially-explicit suitability maps of real and simulated landscapes. Using GRIP 2.0, we carried out a multi-model global sensitivity analysis of a coupled SDM-population dynamics model of whitebark pine (Pinus albicaulis) in Mount Rainier National Park as a case study and quantified the relative influence of input parameters and their interactions on model predictions. Our results differed from the one-at-time analyses used in the original study, and we found that the most influential parameters included the total amount of suitable habitat within the landscape, survival rates, and effects of a prevalent disease, white pine blister rust. Strong interactions between habitat amount and survival rates of older trees suggests the importance of habitat in mediating the negative influences of white pine blister rust. Our results underscore the importance of considering habitat attributes along

  6. Advances in global sensitivity analyses of demographic-based species distribution models to address uncertainties in dynamic landscapes.

    PubMed

    Naujokaitis-Lewis, Ilona; Curtis, Janelle M R

    2016-01-01

    Developing a rigorous understanding of multiple global threats to species persistence requires the use of integrated modeling methods that capture processes which influence species distributions. Species distribution models (SDMs) coupled with population dynamics models can incorporate relationships between changing environments and demographics and are increasingly used to quantify relative extinction risks associated with climate and land-use changes. Despite their appeal, uncertainties associated with complex models can undermine their usefulness for advancing predictive ecology and informing conservation management decisions. We developed a computationally-efficient and freely available tool (GRIP 2.0) that implements and automates a global sensitivity analysis of coupled SDM-population dynamics models for comparing the relative influence of demographic parameters and habitat attributes on predicted extinction risk. Advances over previous global sensitivity analyses include the ability to vary habitat suitability across gradients, as well as habitat amount and configuration of spatially-explicit suitability maps of real and simulated landscapes. Using GRIP 2.0, we carried out a multi-model global sensitivity analysis of a coupled SDM-population dynamics model of whitebark pine (Pinus albicaulis) in Mount Rainier National Park as a case study and quantified the relative influence of input parameters and their interactions on model predictions. Our results differed from the one-at-time analyses used in the original study, and we found that the most influential parameters included the total amount of suitable habitat within the landscape, survival rates, and effects of a prevalent disease, white pine blister rust. Strong interactions between habitat amount and survival rates of older trees suggests the importance of habitat in mediating the negative influences of white pine blister rust. Our results underscore the importance of considering habitat attributes along

  7. Dynamic Trk and G Protein Signalings Regulate Dopaminergic Neurodifferentiation in Human Trophoblast Stem Cells

    PubMed Central

    Lee, Tony Tung-Yin; Tsai, Cheng-Fang; Chen, Hung-Sheng; Lai, Feng-Jie; Yokoyama, Kazunari K.; Hsieh, Tsung-Hsun; Wu, Ruey-Meei; Lee, Jau-nan

    2015-01-01

    Understanding the mechanisms in the generation of neural stem cells from pluripotent stem cells is a fundamental step towards successful management of neurodegenerative diseases in translational medicine. Albeit all-trans retinoic acid (RA) has been associated with axon outgrowth and nerve regeneration, the maintenance of differentiated neurons, the association with degenerative disease like Parkinson's disease, and its regulatory molecular mechanism from pluripotent stem cells to neural stem cells remain fragmented. We have previously reported that RA is capable of differentiation of human trophoblast stem cells to dopamine (DA) committed progenitor cells. Intracranial implantation of such neural progenitor cells into the 6-OHDA-lesioned substantia nigra pars compacta successfully regenerates dopaminergic neurons and integrity of the nigrostriatal pathway, ameliorating the behavioral deficits in the Parkinson’s disease rat model. Here, we demonstrated a dynamic molecular network in systematic analysis by addressing spatiotemporal molecular expression, intracellular protein-protein interaction and inhibition, imaging study, and genetic expression to explore the regulatory mechanisms of RA induction in the differentiation of human trophoblast stem cells to DA committed progenitor cells. We focused on the tyrosine receptor kinase (Trk), G proteins, canonical Wnt2B/β-catenin, genomic and non-genomic RA signaling transductions with Tyrosine hydroxylase (TH) gene expression as the differentiation endpoint. We found that at the early stage, integration of TrkA and G protein signalings aims for axonogenesis and morphogenesis, involving the novel RXRα/Gαq/11 and RARβ/Gβ signaling pathways. While at the later stage, five distinct signaling pathways together with epigenetic histone modifications emerged to regulate expression of TH, a precursor of dopamine. RA induction generated DA committed progenitor cells in one day. Our results provided substantial mechanistic

  8. Dynamic Trk and G Protein Signalings Regulate Dopaminergic Neurodifferentiation in Human Trophoblast Stem Cells.

    PubMed

    Tsai, Eing-Mei; Wang, Yu-Chih; Lee, Tony Tung-Yin; Tsai, Cheng-Fang; Chen, Hung-Sheng; Lai, Feng-Jie; Yokoyama, Kazunari K; Hsieh, Tsung-Hsun; Wu, Ruey-Meei; Lee, Jau-Nan

    2015-01-01

    Understanding the mechanisms in the generation of neural stem cells from pluripotent stem cells is a fundamental step towards successful management of neurodegenerative diseases in translational medicine. Albeit all-trans retinoic acid (RA) has been associated with axon outgrowth and nerve regeneration, the maintenance of differentiated neurons, the association with degenerative disease like Parkinson's disease, and its regulatory molecular mechanism from pluripotent stem cells to neural stem cells remain fragmented. We have previously reported that RA is capable of differentiation of human trophoblast stem cells to dopamine (DA) committed progenitor cells. Intracranial implantation of such neural progenitor cells into the 6-OHDA-lesioned substantia nigra pars compacta successfully regenerates dopaminergic neurons and integrity of the nigrostriatal pathway, ameliorating the behavioral deficits in the Parkinson's disease rat model. Here, we demonstrated a dynamic molecular network in systematic analysis by addressing spatiotemporal molecular expression, intracellular protein-protein interaction and inhibition, imaging study, and genetic expression to explore the regulatory mechanisms of RA induction in the differentiation of human trophoblast stem cells to DA committed progenitor cells. We focused on the tyrosine receptor kinase (Trk), G proteins, canonical Wnt2B/β-catenin, genomic and non-genomic RA signaling transductions with Tyrosine hydroxylase (TH) gene expression as the differentiation endpoint. We found that at the early stage, integration of TrkA and G protein signalings aims for axonogenesis and morphogenesis, involving the novel RXRα/Gαq/11 and RARβ/Gβ signaling pathways. While at the later stage, five distinct signaling pathways together with epigenetic histone modifications emerged to regulate expression of TH, a precursor of dopamine. RA induction generated DA committed progenitor cells in one day. Our results provided substantial mechanistic

  9. Spectral components of laser Doppler flowmetry signals recorded in healthy and type 1 diabetic subjects at rest and during a local and progressive cutaneous pressure application: scalogram analyses

    NASA Astrophysics Data System (ADS)

    Humeau, Anne; Koïtka, Audrey; Abraham, Pierre; Saumet, Jean-Louis; L'Huillier, Jean-Pierre

    2004-09-01

    A significant transient increase in laser Doppler flowmetry (LDF) signals is observed in response to a local and progressive cutaneous pressure application in healthy subjects. This reflex may be impaired in diabetic patients. The work presents a signal processing providing the clarification of this phenomenon. Scalogram analyses of LDF signals recorded at rest and during a local and progressive cutaneous pressure application are performed on healthy and type 1 diabetic subjects. Three frequency bands, corresponding to myogenic, neurogenic and endothelial related metabolic activities, are studied. The results show that, at rest, the scalogram energy of each frequency band is significantly lower for diabetic patients than for healthy subjects, but the scalogram relative energies do not show any statistical difference between the two groups. Moreover, the neurogenic and endothelial related metabolic activities are significantly higher during the progressive pressure than at rest, in healthy and diabetic subjects. However, the relative contribution of the endothelial related metabolic activity is significantly higher during the progressive pressure than at rest, in the interval 200-400 s following the beginning of the pressure application, but only for healthy subjects. These results may improve knowledge on cutaneous microvascular responses to injuries or local pressures initiating diabetic complications.

  10. Molecular characterization and expression analyses of three RIG-I-like receptor signaling pathway genes (MDA5, LGP2 and MAVS) in Larimichthys crocea.

    PubMed

    Shen, Bin; Hu, Yiwen; Zhang, Shuyi; Zheng, Jialang; Zeng, Lin; Zhang, Jianshe; Zhu, Aiyi; Wu, Changwen

    2016-08-01

    In this study, we sequenced and characterized melanoma differentiation-associated antigen 5 (LcMDA5), laboratory of genetics and physiology 2 (LcLGP2) and mitochondrial antiviral signaling protein (LcMAVS) from large yellow croaker (Larimichthys crocea). The LcMDA5 encodes 969 amino acids and contains two caspase-associated and recruitment domains (CARDs), a DExDc (DExD/H box-containing domain), a HELICc (helicase superfamily C-terminal domain) and a C-terminal regulatory domain (RD). The LcLGP2 encodes 679 amino acids and contains a DExDc, a HELICc and a RD. The LcMAVS encodes 512 amino acids and contains a CARD, a proline-rich domain, a transmembrane helix domain and a putative TRAF2-binding motif ((269)PVQDT(273)). Phylogenetic analyses showed that all the three genes of large yellow croaker are clustered together with their counterparts from other teleost fishes. The Real-time PCR analyses showed that all the three genes were found to be constitutively expressed in all examined tissues in large yellow croaker, but all with relatively low expression levels. Expression analyses showed that the three genes were all rapidly and significantly upregulated in vivo after poly (I:C) challenge in peripheral blood, liver, spleen and head kidney tissues. The results indicate that the LcMDA5, LcLGP2 and LcMAVS might play important roles in antiviral immune responses. PMID:27346150

  11. Impact of signaling microcompartment geometry on GPCR dynamics in live retinal photoreceptors.

    PubMed

    Najafi, Mehdi; Haeri, Mohammad; Knox, Barry E; Schiesser, William E; Calvert, Peter D

    2012-09-01

    G protein-coupled receptor (GPCR) cascades rely on membrane protein diffusion for signaling and are generally found in spatially constrained subcellular microcompartments. How the geometry of these microcompartments impacts cascade activities, however, is not understood, primarily because of the inability of current live cell-imaging technologies to resolve these small structures. Here, we examine the dynamics of the GPCR rhodopsin within discrete signaling microcompartments of live photoreceptors using a novel high resolution approach. Rhodopsin fused to green fluorescent protein variants, either enhanced green fluorescent protein (EGFP) or the photoactivatable PAGFP (Rho-E/PAGFP), was expressed transgenically in Xenopus laevis rod photoreceptors, and the geometries of light signaling microcompartments formed by lamellar disc membranes and their incisure clefts were resolved by confocal imaging. Multiphoton fluorescence relaxation after photoconversion experiments were then performed with a Ti-sapphire laser focused to the diffraction limit, which produced small sub-cubic micrometer volumes of photoconverted molecules within the discrete microcompartments. A model of molecular diffusion was developed that allows the geometry of the particular compartment being examined to be specified. This was used to interpret the experimental results. Using this unique approach, we showed that rhodopsin mobility across the disc surface was highly heterogeneous. The overall relaxation of Rho-PAGFP fluorescence photoactivated within a microcompartment was biphasic, with a fast phase lasting several seconds and a slow phase of variable duration that required up to several minutes to reach equilibrium. Local Rho-EGFP diffusion within defined compartments was monotonic, however, with an effective lateral diffusion coefficient D(lat) = 0.130 ± 0.012 µm(2)s(-1). Comparison of rhodopsin-PAGFP relaxation time courses with model predictions revealed that microcompartment geometry alone

  12. The Signaling Petri Net-Based Simulator: A Non-Parametric Strategy for Characterizing the Dynamics of Cell-Specific Signaling Networks

    PubMed Central

    Ruths, Derek; Muller, Melissa; Tseng, Jen-Te; Nakhleh, Luay; Ram, Prahlad T.

    2008-01-01

    Reconstructing cellular signaling networks and understanding how they work are major endeavors in cell biology. The scale and complexity of these networks, however, render their analysis using experimental biology approaches alone very challenging. As a result, computational methods have been developed and combined with experimental biology approaches, producing powerful tools for the analysis of these networks. These computational methods mostly fall on either end of a spectrum of model parameterization. On one end is a class of structural network analysis methods; these typically use the network connectivity alone to generate hypotheses about global properties. On the other end is a class of dynamic network analysis methods; these use, in addition to the connectivity, kinetic parameters of the biochemical reactions to predict the network's dynamic behavior. These predictions provide detailed insights into the properties that determine aspects of the network's structure and behavior. However, the difficulty of obtaining numerical values of kinetic parameters is widely recognized to limit the applicability of this latter class of methods. Several researchers have observed that the connectivity of a network alone can provide significant insights into its dynamics. Motivated by this fundamental observation, we present the signaling Petri net, a non-parametric model of cellular signaling networks, and the signaling Petri net-based simulator, a Petri net execution strategy for characterizing the dynamics of signal flow through a signaling network using token distribution and sampling. The result is a very fast method, which can analyze large-scale networks, and provide insights into the trends of molecules' activity-levels in response to an external stimulus, based solely on the network's connectivity. We have implemented the signaling Petri net-based simulator in the PathwayOracle toolkit, which is publicly available at http://bioinfo.cs.rice.edu/pathwayoracle. Using

  13. Detection, Evaluation, and Optimization of Optical Signals Generated by Fiber Optic Bragg Gratings Under Dynamic Excitations

    NASA Technical Reports Server (NTRS)

    Adamovsky, Grigory; Lekki, John; Lock, James A.

    2002-01-01

    The dynamic response of a fiber optic Bragg grating to mechanical vibrations is examined both theoretically and experimentally. The theoretical expressions describing the consequences of changes in the grating's reflection spectrum are derived for partially coherent beams in an interferometer. The analysis is given in terms of the dominant wavelength, optical bandwidth, and optical path difference of the interfering signals. Changes in the reflection spectrum caused by a periodic stretching and compression of the grating were experimentally measured using an unbalanced Michelson interferometer, a Michelson interferometer with a non-zero optical path difference. The interferometer's sensitivity to changes in dominant wavelength of the interfering beams was measured as a function of interferometer unbalance and was compared to theoretical predictions. The theoretical analysis enables the user to determine the optimum performance for an unbalanced interferometer.

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

    NASA Astrophysics Data System (ADS)

    Kremliovsky, Michael; Kadtke, James

    1996-06-01

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

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

    SciTech Connect

    Kremliovsky, M.; Kadtke, J.

    1996-06-01

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

  16. Clock signal requirement for high-frequency, high dynamic range acquisition systems

    SciTech Connect

    Viscor, Ivo; Halamek, Josef; Villa, Marco

    2005-11-15

    Analog-to-digital converters (ADC's) are increasingly replacing mixers in frequency conversion schemes. To achieve superior performances, in terms of bandwidth and dynamic range, a nearly ideal ADC clock is needed, with a spectral purity higher than the reference signal of the classical mixing scheme. These requirements of spectral purity for the ADC clock are discussed by analyzing in detail the nonuniform sampling process and by characterizing an actual acquisition system. The effect of clock phase imperfections on the output is proportional to the input frequency over sampling frequency ratio. Moreover, at the output we may have a multiple folding of the phase jitter spectrum. These effects are illustrated by three sets of measurements performed using our system: transfer of spurious clock components, aliasing of these components, and transfer of clock phase noise.

  17. Current-induced atomic dynamics, instabilities, and Raman signals: Quasiclassical Langevin equation approach

    NASA Astrophysics Data System (ADS)

    Lü, Jing-Tao; Brandbyge, Mads; Hedegård, Per; Todorov, Tchavdar N.; Dundas, Daniel

    2012-06-01

    We derive and employ a semiclassical Langevin equation obtained from path integrals to describe the ionic dynamics of a molecular junction in the presence of electrical current. The electronic environment serves as an effective nonequilibrium bath. The bath results in random forces describing Joule heating, current-induced forces including the nonconservative wind force, dissipative frictional forces, and an effective Lorentz-type force due to the Berry phase of the nonequilibrium electrons. Using a generic two-level molecular model, we highlight the importance of both current-induced forces and Joule heating for the stability of the system. We compare the impact of the different forces, and the wide-band approximation for the electronic structure on our result. We examine the current-induced instabilities (excitation of runaway “waterwheel” modes) and investigate the signature of these in the Raman signals.

  18. NIR fibre Bragg grating as dynamic sensor: an application of 1D digital wavelet analysis for signal denoising

    NASA Astrophysics Data System (ADS)

    Hafizi, Z. M.; Kahandawa, G. C.; Epaarachchi, J.; Lau, K. T.; Canning, J.; Cook, K.

    2013-08-01

    During the past decade, many successful studies have evidently shown remarkable capability of Fiber Bragg Gratings (FBG) sensor for dynamic sensing. Most of the research works utilized the 1550 nm wavelength range of FBG sensors. However near infra-red (NIR) FBG sensors can offer the lower cost of Structural health Monitoring (SHM) systems which uses cheaper silicon sources and detectors. Unfortunately, the excessive noise levels that experienced in NIR wavelengths have caused the rejection of sensor that operating in this range of wavelengths for SHM systems. However, with the appropriate use of signal processing tools, these noisy signals can be easily `cleaned'. Wavelet analysis is one of the powerful signal processing tools nowadays, not only for time-frequency analysis but also for signal denoising. This present study revealed that the NIR FBG range gave good response to impact signals. Furthermore, these `noisy' signals' response were successfully filtered using one dimensional wavelet analysis.

  19. Introducing a rain-adjusted vegetation index (RAVI) for improvement of long-term trend analyses in vegetation dynamics

    NASA Astrophysics Data System (ADS)

    Wessollek, Christine; Karrasch, Pierre; Osunmadewa, Babatunde

    2015-10-01

    It seems to be obvious that precipitation has a major impact on greening during the rainy season in semi-arid regions. First results1 imply a strong dependence of NDVI on rainfall. Therefore it will be necessary to consider specific rainfall events besides the known ordinary annual cycle. Based on this fundamental idea, the paper will introduce the development of a rain adjusted vegetation index (RAVI). The index is based on the enhancement of the well-known normalized difference vegetation index (NDVI2) by means of TAMSAT rainfall data and includes a 3-step procedure of determining RAVI. Within the first step both time series were analysed over a period of 29 years to find best cross correlation values between TAMSAT rainfall and NDVI signal itself. The results indicate the strongest correlation for a weighted mean rainfall for a period of three months before the corresponding NDVI value. Based on these results different mathematical models (linear, logarithmic, square root, etc.) are tested to find a functional relation between the NDVI value and the 3-months rainfall period before (0.8). Finally, the resulting NDVI-Rain-Model can be used to determine a spatially individual correction factor to transform every NDVI value into an appropriate rain adjusted vegetation index (RAVI).

  20. Global transcriptome analyses provide evidence that chloroplast redox state contributes to intracellular as well as long-distance signalling in response to stress and acclimation in Arabidopsis.

    PubMed

    Bode, Rainer; Ivanov, Alexander G; Hüner, Norman P A

    2016-06-01

    Global transcriptome analyses were used to assess the interactive effects of short-term stress versus long-term acclimation to high light (HL), low temperature (LT) and excitation pressure in Arabidopsis. Microarray analyses indicated that exposure to stress resulted in two times as many modulated transcripts in both, high-light-treated and low-temperature-treated plants, compared to plants that were fully acclimated to either one of these conditions. We showed that 10.9 % of all transcripts were regulated in the same way by both stress conditions, and hence, were categorized as excitation pressure regulated, rather than regulated by either high-light or low-temperature stress per se. This group of chloroplast redox-sensitive genes included various photosynthetic genes as well as genes known to be associated with cold acclimation (cbf3, cor15A, cor15B) and gibberellic acid (GA) metabolism and signalling (ga2ox1, gai). Chemical inhibition of the photosynthetic electron transport by either DCMU or DBMIB indicated that although the plastoquinone pool contributes significantly to redox regulation of the transcriptome (8.6 %), it appears that PSI represents the major source of redox signals (89 %), whereas PSII appears to contribute only 3.1 %. A comparison of the gene expression profiles between stress and acclimated plants indicated that 10 % of the genes induced by a short, 1-h stress were also associated with long-term acclimation to high excitation pressure. This included the APETALA2/ETHYLENE-RESPONSIVE-BINDING PROTEIN family, the MYB domain- and MYB-related transcription factor family as well as the GRAS transcription factor family important in GA signalling confirming that acclimation to stress is a time-nested phenomenon. We suggest that acclimation to photosynthetic redox imbalance extends beyond the chloroplast and the leaf cell to systemic ROS signalling. This is discussed in terms of the control of plant phenotype through regulation of the nuclear

  1. Dynamics of a microbial community associated with manure hot spots as revealed by phospholipid fatty acid analyses.

    PubMed Central

    Frostegård, A; Petersen, S O; Bååth, E; Nielsen, T H

    1997-01-01

    Microbial community dynamics associated with manure hot spots were studied by using a model system consisting of a gel-stabilized mixture of soil and manure, placed between layers of soil, during a 3-week incubation period. The microbial biomass, measured as the total amount of phospholipid fatty acids (PLFA), had doubled within a 2-mm distance from the soil-manure interface after 3 days. Principal-component analyses demonstrated that this increase was accompanied by reproducible changes in the composition of PLFA, indicating changes in the microbial community structure. The effect of the manure was strongest in the 2-mm-thick soil layer closest to the interface, in which the PLFA composition was statistically significantly different (P < 0.05) from that of the unaffected soil layers throughout the incubation period. An effect was also observed in the soil layer 2 to 4 mm from the interface. The changes in microbial biomass and community structure were mainly attributed to the diffusion of dissolved organic carbon from the manure. During the initial period of microbial growth, PLFA, which were already more abundant in the manure than in the soil, increased in the manure core and in the 2-mm soil layer closest to the interface. After day 3, the PLFA composition of these layers gradually became more similar to that of the soil. The dynamics of individual PLFA suggested that both taxonomic and physiological changes occurred during growth. Examples of the latter were decreases in the ratios of 16:1 omega 7t to 16:1 omega 7c and of cyclopropyl fatty acids to their respective precursors, indicating a more active bacterial community. An inverse relationship between bacterial PLFA and the eucaryotic 20:4 PLFA (arachidonic acid) suggested that grazing was important. PMID:9172342

  2. Cdc42/N-WASP signaling links actin dynamics to pancreatic β cell delamination and differentiation

    PubMed Central

    Kesavan, Gokul; Lieven, Oliver; Mamidi, Anant; Öhlin, Zarah Löf; Johansson, Jenny Kristina; Li, Wan-Chun; Lommel, Silvia; Greiner, Thomas Uwe; Semb, Henrik

    2014-01-01

    Delamination plays a pivotal role during normal development and cancer. Previous work has demonstrated that delamination and epithelial cell movement within the plane of an epithelium are associated with a change in cellular phenotype. However, how this positional change is linked to differentiation remains unknown. Using the developing mouse pancreas as a model system, we show that β cell delamination and differentiation are two independent events, which are controlled by Cdc42/N-WASP signaling. Specifically, we show that expression of constitutively active Cdc42 in β cells inhibits β cell delamination and differentiation. These processes are normally associated with junctional actin and cell-cell junction disassembly and the expression of fate-determining transcription factors, such as Isl1 and MafA. Mechanistically, we demonstrate that genetic ablation of N-WASP in β cells expressing constitutively active Cdc42 partially restores both delamination and β cell differentiation. These findings elucidate how junctional actin dynamics via Cdc42/N-WASP signaling cell-autonomously control not only epithelial delamination but also cell differentiation during mammalian organogenesis. PMID:24449844

  3. Novel Pseudo-Wavelet Function for MMG Signal Extraction during Dynamic Fatiguing Contractions

    PubMed Central

    Al-Mulla, Mohamed R.; Sepulveda, Francisco

    2014-01-01

    The purpose of this study was to develop an algorithm to classify muscle fatigue content in sports related scenarios. Mechanomyography (MMG) signals of the biceps muscle were recorded from thirteen subjects performing dynamic contractions until fatigue. For training and testing purposes, the signals were labeled in two classes (Non-Fatigue and Fatigue). A genetic algorithm was used to evolve a pseudo-wavelet function for optimizing the detection of muscle fatigue. Tuning of the generalized evolved pseudo-wavelet function was based on the decomposition of 70% of the conducted MMG trials. After completing 25 independent pseudo-wavelet evolution runs, the best run was selected and then tested on the remaining 30% of the data to measure the classification performance. Results show that the evolved pseudo-wavelet improved the classification rate of muscle fatigue by 4.70 percentage points to 16.61 percentage points when compared to other standard wavelet functions, giving an average correct classification of 80.63%, with statistical significance (p < 0.05). PMID:24878591

  4. Live cell micropatterning reveals the dynamics of signaling complexes at the plasma membrane.

    PubMed

    Löchte, Sara; Waichman, Sharon; Beutel, Oliver; You, Changjiang; Piehler, Jacob

    2014-11-10

    Interactions of proteins in the plasma membrane are notoriously challenging to study under physiological conditions. We report in this paper a generic approach for spatial organization of plasma membrane proteins into micropatterns as a tool for visualizing and quantifying interactions with extracellular, intracellular, and transmembrane proteins in live cells. Based on a protein-repellent poly(ethylene glycol) polymer brush, micropatterned surface functionalization with the HaloTag ligand for capturing HaloTag fusion proteins and RGD peptides promoting cell adhesion was devised. Efficient micropatterning of the type I interferon (IFN) receptor subunit IFNAR2 fused to the HaloTag was achieved, and highly specific IFN binding to the receptor was detected. The dynamics of this interaction could be quantified on the single molecule level, and IFN-induced receptor dimerization in micropatterns could be monitored. Assembly of active signaling complexes was confirmed by immunostaining of phosphorylated Janus family kinases, and the interaction dynamics of cytosolic effector proteins recruited to the receptor complex were unambiguously quantified by fluorescence recovery after photobleaching. PMID:25385185

  5. Systematic parameter estimation in data-rich environments for cell signalling dynamics

    PubMed Central

    Nim, Tri Hieu; Luo, Le; Clément, Marie-Véronique; White, Jacob K.; Tucker-Kellogg, Lisa

    2013-01-01

    Motivation: Computational models of biological signalling networks, based on ordinary differential equations (ODEs), have generated many insights into cellular dynamics, but the model-building process typically requires estimating rate parameters based on experimentally observed concentrations. New proteomic methods can measure concentrations for all molecular species in a pathway; this creates a new opportunity to decompose the optimization of rate parameters. Results: In contrast with conventional parameter estimation methods that minimize the disagreement between simulated and observed concentrations, the SPEDRE method fits spline curves through observed concentration points, estimates derivatives and then matches the derivatives to the production and consumption of each species. This reformulation of the problem permits an extreme decomposition of the high-dimensional optimization into a product of low-dimensional factors, each factor enforcing the equality of one ODE at one time slice. Coarsely discretized solutions to the factors can be computed systematically. Then the discrete solutions are combined using loopy belief propagation, and refined using local optimization. SPEDRE has unique asymptotic behaviour with runtime polynomial in the number of molecules and timepoints, but exponential in the degree of the biochemical network. SPEDRE performance is comparatively evaluated on a novel model of Akt activation dynamics including redox-mediated inactivation of PTEN (phosphatase and tensin homologue). Availability and implementation: Web service, software and supplementary information are available at www.LtkLab.org/SPEDRE Supplementary information: Supplementary data are available at Bioinformatics online. Contact: LisaTK@nus.edu.sg PMID:23426255

  6. Regulation of Structural Dynamics within a Signal Recognition Particle Promotes Binding of Protein Targeting Substrates*

    PubMed Central

    Gao, Feng; Kight, Alicia D.; Henderson, Rory; Jayanthi, Srinivas; Patel, Parth; Murchison, Marissa; Sharma, Priyanka; Goforth, Robyn L.; Kumar, Thallapuranam Krishnaswamy Suresh; Henry, Ralph L.; Heyes, Colin D.

    2015-01-01

    Protein targeting is critical in all living organisms and involves a signal recognition particle (SRP), an SRP receptor, and a translocase. In co-translational targeting, interactions among these proteins are mediated by the ribosome. In chloroplasts, the light-harvesting chlorophyll-binding protein (LHCP) in the thylakoid membrane is targeted post-translationally without a ribosome. A multidomain chloroplast-specific subunit of the SRP, cpSRP43, is proposed to take on the role of coordinating the sequence of targeting events. Here, we demonstrate that cpSRP43 exhibits significant interdomain dynamics that are reduced upon binding its SRP binding partner, cpSRP54. We showed that the affinity of cpSRP43 for the binding motif of LHCP (L18) increases when cpSRP43 is complexed to the binding motif of cpSRP54 (cpSRP54pep). These results support the conclusion that substrate binding to the chloroplast SRP is modulated by protein structural dynamics in which a major role of cpSRP54 is to improve substrate binding efficiency to the cpSRP. PMID:25918165

  7. Changes in actin dynamics are involved in salicylic acid signaling pathway.

    PubMed

    Matoušková, Jindřiška; Janda, Martin; Fišer, Radovan; Sašek, Vladimír; Kocourková, Daniela; Burketová, Lenka; Dušková, Jiřina; Martinec, Jan; Valentová, Olga

    2014-06-01

    Changes in actin cytoskeleton dynamics are one of the crucial players in many physiological as well as non-physiological processes in plant cells. Positioning of actin filament arrays is necessary for successful establishment of primary lines of defense toward pathogen attack, depolymerization leads very often to the enhanced susceptibility to the invading pathogen. On the other hand it was also shown that the disruption of actin cytoskeleton leads to the induction of defense response leading to the expression of PATHOGENESIS RELATED proteins (PR). In this study we show that pharmacological actin depolymerization leads to the specific induction of genes in salicylic acid pathway but not that involved in jasmonic acid signaling. Life imaging of leafs of Arabidopsis thaliana with GFP-tagged fimbrin (GFP-fABD2) treated with 1 mM salicylic acid revealed rapid disruption of actin filaments resembling the pattern viewed after treatment with 200 nM latrunculin B. The effect of salicylic acid on actin filament fragmentation was prevented by exogenous addition of phosphatidic acid, which binds to the capping protein and thus promotes actin polymerization. The quantitative evaluation of actin filament dynamics is also presented. PMID:24767113

  8. Clustering in Cell Cycle Dynamics with General Response/Signaling Feedback

    PubMed Central

    Young, Todd R.; Fernandez, Bastien; Buckalew, Richard; Moses, Gregory; Boczko, Erik M.

    2011-01-01

    Motivated by experimental and theoretical work on autonomous oscillations in yeast, we analyze ordinary differential equations models of large populations of cells with cell-cycle dependent feedback. We assume a particular type of feedback that we call Responsive/Signaling (RS), but do not specify a functional form of the feedback. We study the dynamics and emergent behaviour of solutions, particularly temporal clustering and stability of clustered solutions. We establish the existence of certain periodic clustered solutions as well as “uniform” solutions and add to the evidence that cell-cycle dependent feedback robustly leads to cell-cycle clustering. We highlight the fundamental differences in dynamics between systems with negative and positive feedback. For positive feedback systems the most important mechanism seems to be the stability of individual isolated clusters. On the other hand we find that in negative feedback systems, clusters must interact with each other to reinforce coherence. We conclude from various details of the mathematical analysis that negative feedback is most consistent with observations in yeast experiments. PMID:22001733

  9. Dynamical Analyses of z=0.3,0.5 Galaxy Clusters from the SOAR Gravitational Arcs Survey

    NASA Astrophysics Data System (ADS)

    Cibirka, N.; Cypriano, E.; Caminha, G.; Makler, M.

    2014-10-01

    We have performed dynamical analyses of galaxy clusters using optical spectroscopic data. These clusters belong to the SOAR Gravitational Arcs Survey (SOGRAS) (Furlanetto et al. 2013) and are among the richest structures in SDSS stripe 82 with redshifts around z=0.3 or z=0.5. For three of those clusters, all with strong lensing features, we carried out individual analysis using Gemini/GMOS data (˜ 25 velocities per cluster). We obtained masses in the range of 3-8 × 10^{14} M_{odot } and signs of substructure in one of them. For the whole SOGRAS sample (47 clusters) we used SDSS spectroscopic data. Given the low number of velocities per clusters, we stacked the data per redshift and/or richness. Our results indicate that the richest half of the clusters, independently of the redshift, tend to be ˜ 2.5 times more massive than the poorest half. Also we have found that the z=0.3 and the z=0.5 clusters have overall masses statistically consistent with each other: 6.3(^{+3.9}_{-2.1}) and 8.6(^{+5.2}_{-1.6}) × 10^{14} M_{odot} respectively.

  10. Analyses of Dynamic Response of Vehicle and Track Coupling System with Random Irregularity of Track Vertical Profile

    NASA Astrophysics Data System (ADS)

    LEI, X.; NODA, N.-A.

    2002-11-01

    A dynamic computational model for the vehicle and track coupling system is developed by means of finite element method in this paper. In numerical implementation, the vehicle and track coupling system is divided into two parts; lower structure and upper structure. The vehicle as the upper structure in the coupling system is a whole locomotive or rolling stock with two layers of spring and damping system in which vertical and rolling motion for vehicle and bogie are involved. The lower structure in the coupling system is a railway track where rails are considered as beams with finite length rested on a double layer continuous elastic foundation. The two parts are solved independently with an iterative scheme. Coupling the vehicle system and railway track is realized through interaction forces between the wheels and the rail, where the irregularity of the track vertical profile considered as stationary ergodic Gaussian random processes and simulated by trigonometry series is included. The amplitudes of vibrations, their velocities and the accelerations generated in the vehicle and rail and the interaction forces between the vehicle and the rail due to the random irregularity of the track vertical profile and different line grades and train speeds have been analyzed numerically by this model. Analyses of system responses are performed in time and frequency domains.

  11. Time point-based integrative analyses of deep-transcriptome identify four signal pathways in blastemal regeneration of zebrafish lower jaw.

    PubMed

    Zhang, Hui; Wang, Xuelong; Lyu, Kailun; Gao, Siqi; Wang, Guan; Fan, Chunxin; Zhang, Xin A; Yan, Jizhou

    2015-03-01

    There has been growing interest in applying tissue engineering to stem cell-based regeneration therapies. We have previously reported that zebrafish can faithfully regenerate complicated tissue structures through blastemal cell type conversions and tissue reorganization. To unveil the regenerative factors and engineering arts of blastemal regeneration, we conducted transcriptomal analyses at four time points corresponding to preamputation, re-epitheliation, blastemal formation, and respecification. By combining the hierarchical gene ontology term network, the DAVID annotation system, and Euclidean distance clustering, we identified four signaling pathways: foxi1-foxo1b-pou3f1, pax3a-mant3a-col11/col2, pou5f1-cdx4-kdrl, and isl1-wnt11 PCP-sox9a. Results from immunohistochemical staining and promoter-driven transgenic fish suggest that these pathways, respectively, define wound epidermis reconstitution, cell type conversions, blastemal angiogenesis/vasculogenesis, and cartilage matrix-orientation. Foxi1 morpholino-knockdown caused expansions of Foxo1b- and Pax3a-expression in the basal layer-blastemal junction region. Moreover, foxi1 morphants displayed increased sox9a and hoxa2b transcripts in the embryonic pharyngeal arches. Thus, a Foxi1 signal switch is required to establish correct tissue patterns, including re-epitheliation and blastema formation. This study provides novel insight into a blastema regeneration strategy devised by epithelial cell transdifferentiation, blood vessel engineering, and cartilage matrix deposition. PMID:25420467

  12. Molecular Dynamics Underlie the Nature of MRI Signals: The NMR Shutter-Speed

    NASA Astrophysics Data System (ADS)

    Springer, Charles S., Jr.

    2007-03-01

    Motions of the spin-bearing molecules can have profound effects on the very nature (the exponentiality) of the macroscopic NMR signal. Quantitative mechanistic protocols often involve varying the equilibrium molecular kinetics (usually by temperature change) relative to the ``NMR time-scale'' (SS-1), usually ill-defined as the absolute difference of resonance frequencies [|δφ|] in sites between which spins are exchanged. This holds true for the equilibrium water molecule exchange between tissue compartments and distinct populations. However, in vivo studies must [by regulation] be isothermal, and the tissue ^1H2O MRI signals remain essentially isochronous [δφ = 0]. In NMR, an equilibrium process is manifest in the context of its ``exchange condition.'' It only ``appears'' to be fast or slow by comparison of its actual rate constant with its system ``shutter-speed'' (SS). [A nonzero δφ is the first, but not only, SS: its dimension is reciprocal time.] The process kinetics can be measured only if its NMR condition is varied at least partway between the fast- and slow exchange limits. In an isothermal study with no catalyst, this can be accomplished only by varying the pertinent SS. An MRI contrast reagent (CR) increases the laboratory frame ^1H2O relaxation rate constant, Ri [≡ (Ti)-1; i = 1,2]. For an isochronous exchange process, the SS is the intrinsic |δRi| for the sites. In quantitative dynamic-contrast-enhanced (DCE) studies, analytical pharmacokinetic modeling is accomplished on region-of-interest (ROI) or pixel by pixel ^1H2O signal time-courses following bolus CR injections. Accounting for the equilibrium transendothelial and transcytolemmal water interchange processes (a three-site exchange situation) is crucial for modeling accuracy: the relevant SS values vary during the CR bolus passage. This is so for DCE studies of cancer, multiple sclerosis, and myocardial blood flow variation. It is necessary for the successful discrimination of malignant

  13. Wavelet Analyses and Applications

    ERIC Educational Resources Information Center

    Bordeianu, Cristian C.; Landau, Rubin H.; Paez, Manuel J.

    2009-01-01

    It is shown how a modern extension of Fourier analysis known as wavelet analysis is applied to signals containing multiscale information. First, a continuous wavelet transform is used to analyse the spectrum of a nonstationary signal (one whose form changes in time). The spectral analysis of such a signal gives the strength of the signal in each…

  14. Distinct Sonic Hedgehog signaling dynamics specify floor plate and ventral neuronal progenitors in the vertebrate neural tube

    PubMed Central

    Ribes, Vanessa; Balaskas, Nikolaos; Sasai, Noriaki; Cruz, Catarina; Dessaud, Eric; Cayuso, Jordi; Tozer, Samuel; Yang, Lin Lin; Novitch, Ben; Marti, Elisa; Briscoe, James

    2010-01-01

    The secreted ligand Sonic Hedgehog (Shh) organizes the pattern of cellular differentiation in the ventral neural tube. For the five neuronal subtypes, increasing levels and durations of Shh signaling direct progenitors to progressively more ventral identities. Here we demonstrate that this mode of action is not applicable to the generation of the most ventral cell type, the nonneuronal floor plate (FP). In chick and mouse embryos, FP specification involves a biphasic response to Shh signaling that controls the dynamic expression of key transcription factors. During gastrulation and early somitogenesis, FP induction depends on high levels of Shh signaling. Subsequently, however, prospective FP cells become refractory to Shh signaling, and this is a prerequisite for the elaboration of their identity. This prompts a revision to the model of graded Shh signaling in the neural tube, and provides insight into how the dynamics of morphogen signaling are deployed to extend the patterning capacity of a single ligand. In addition, we provide evidence supporting a common scheme for FP specification by Shh signaling that reconciles mechanisms of FP development in teleosts and amniotes. PMID:20516201

  15. Analyses of Magnetic Resonance Imaging of Cerebrospinal Fluid Dynamics Pre and Post Short and Long-Duration Space Flights

    NASA Technical Reports Server (NTRS)

    Alperin, Noam; Barr, Yael; Lee, Sang H.; Mason,Sara; Bagci, Ahmet M.

    2015-01-01

    Preliminary results are based on analyses of data from 17 crewmembers. The initial analysis compares pre to post-flight changes in total cerebral blood flow (CBF) and craniospinal CSF flow volume. Total CBF is obtained by summation of the mean flow rates through the 4 blood vessels supplying the brain (right and left internal carotid and vertebral arteries). Volumetric flow rates were obtained using an automated lumen segmentation technique shown to have 3-4-fold improved reproducibility and accuracy over manual lumen segmentation (6). Two cohorts, 5 short-duration and 8 long-duration crewmembers, who were scanned within 3 to 8 days post landing were included (4 short-duration crewmembers with MRI scans occurring beyond 10 days post flight were excluded). The VIIP Clinical Practice Guideline (CPG) classification is being used initially as a measure for VIIP syndrome severity. Median CPG scores of the short and long-duration cohorts were similar, 2. Mean preflight total CBF for the short and long-duration cohorts were similar, 863+/-144 and 747+/-119 mL/min, respectively. Percentage CBF changes for all short duration crewmembers were 11% or lower, within the range of normal physiological fluctuations in healthy individuals. In contrast, in 4 of the 8 long-duration crewmembers, the change in CBF exceeded the range of normal physiological fluctuation. In 3 of the 4 subjects an increase in CBF was measured. Large pre to post-flight changes in the craniospinal CSF flow volume were found in 6 of the 8 long-duration crewmembers. Box-Whisker plots of the CPG and the percent CBF and CSF flow changes for the two cohorts are shown in Figure 4. Examples of CSF flow waveforms for a short and two long-duration (CPG 0 and 3) are shown in Figure 5. Changes in CBF and CSF flow dynamics larger than normal physiological fluctuations were observed in the long-duration crewmembers. Changes in CSF flow were more pronounced than changes in CBF. Decreased CSF flow dynamics were observed

  16. Developmental maturation of dynamic causal control signals in higher-order cognition: a neurocognitive network model.

    PubMed

    Supekar, Kaustubh; Menon, Vinod

    2012-02-01

    Cognitive skills undergo protracted developmental changes resulting in proficiencies that are a hallmark of human cognition. One skill that develops over time is the ability to problem solve, which in turn relies on cognitive control and attention abilities. Here we use a novel multimodal neurocognitive network-based approach combining task-related fMRI, resting-state fMRI and diffusion tensor imaging (DTI) to investigate the maturation of control processes underlying problem solving skills in 7-9 year-old children. Our analysis focused on two key neurocognitive networks implicated in a wide range of cognitive tasks including control: the insula-cingulate salience network, anchored in anterior insula (AI), ventrolateral prefrontal cortex and anterior cingulate cortex, and the fronto-parietal central executive network, anchored in dorsolateral prefrontal cortex and posterior parietal cortex (PPC). We found that, by age 9, the AI node of the salience network is a major causal hub initiating control signals during problem solving. Critically, despite stronger AI activation, the strength of causal regulatory influences from AI to the PPC node of the central executive network was significantly weaker and contributed to lower levels of behavioral performance in children compared to adults. These results were validated using two different analytic methods for estimating causal interactions in fMRI data. In parallel, DTI-based tractography revealed weaker AI-PPC structural connectivity in children. Our findings point to a crucial role of AI connectivity, and its causal cross-network influences, in the maturation of dynamic top-down control signals underlying cognitive development. Overall, our study demonstrates how a unified neurocognitive network model when combined with multimodal imaging enhances our ability to generalize beyond individual task-activated foci and provides a common framework for elucidating key features of brain and cognitive development. The

  17. Temporal dynamics in an immunological synapse: Role of thermal fluctuations in signaling

    NASA Astrophysics Data System (ADS)

    Bush, Daniel R.; Chattopadhyay, Amit K.

    2015-07-01

    The article analyzes the contribution of stochastic thermal fluctuations in the attachment times of the immature T-cell receptor TCR: peptide-major-histocompatibility-complex pMHC immunological synapse bond. The key question addressed here is the following: how does a synapse bond remain stabilized in the presence of high-frequency thermal noise that potentially equates to a strong detaching force? Focusing on the average time persistence of an immature synapse, we show that the high-frequency nodes accompanying large fluctuations are counterbalanced by low-frequency nodes that evolve over longer time periods, eventually leading to signaling of the immunological synapse bond primarily decided by nodes of the latter type. Our analysis shows that such a counterintuitive behavior could be easily explained from the fact that the survival probability distribution is governed by two distinct phases, corresponding to two separate time exponents, for the two different time regimes. The relatively shorter timescales correspond to the cohesion:adhesion induced immature bond formation whereas the larger time reciprocates the association:dissociation regime leading to TCR:pMHC signaling. From an estimate of the bond survival probability, we show that, at shorter timescales, this probability PΔ(τ ) scales with time τ as a universal function of a rescaled noise amplitude D/Δ2, such that PΔ(τ ) ˜τ-(Δ/√{D }+1/2 ) ,Δ being the distance from the mean intermembrane (T cell:Antigen Presenting Cell) separation distance. The crossover from this shorter to a longer time regime leads to a universality in the dynamics, at which point the survival probability shows a different power-law scaling compared to the one at shorter timescales. In biological terms, such a crossover indicates that the TCR:pMHC bond has a survival probability with a slower decay rate than the longer LFA-1:ICAM-1 bond justifying its stability.

  18. Dynamics of β-adrenergic/cAMP signaling and morphological changes in cultured astrocytes.

    PubMed

    Vardjan, Nina; Kreft, Marko; Zorec, Robert

    2014-04-01

    The morphology of astrocytes, likely regulated by cAMP, determines the structural association between astrocytes and the synapse, consequently modulating synaptic function. β-Adrenergic receptors (β-AR), which increase cytosolic cAMP concentration ([cAMP]i ), may affect cell morphology. However, the real-time dynamics of β-AR-mediated cAMP signaling in single live astrocytes and its effect on cell morphology have not been studied. We used the fluorescence resonance energy transfer (FRET)-based cAMP biosensor Epac1-camps to study time-dependent changes in [cAMP]i ; morphological changes in primary rat astrocytes were monitored by real-time confocal microscopy. Stimulation of β-AR by adrenaline, noradrenaline, and isoprenaline, a specific agonist of β-AR, rapidly increased [cAMP]i (∼15 s). The FRET signal response, mediated via β-AR, was faster than in the presence of forskolin (twofold) and dibutyryl-cAMP (>35-fold), which directly activate adenylyl cyclase and Epac1-camps, respectively, likely due to slow entry of these agents into the cytosol. Oscillations in [cAMP]i have not been recorded, indicating that cAMP-dependent processes operate in a slow time domain. Most Epac1-camps expressing astrocytes revealed a morphological change upon β-AR activation and attained a stellate morphology within 1 h. The morphological changes exhibited a bell-shaped dependency on [cAMP]i . The 5-10% decrease in cell cross-sectional area and the 30-50% increase in cell perimeter are likely due to withdrawal of the cytoplasm to the perinuclear region and the appearance of protrusions on the surface of astrocytes. Because astrocyte processes ensheath neurons, β-AR/cAMP-mediated morphological changes can modify the geometry of the extracellular space, affecting synaptic, neuronal, and astrocyte functions in health and disease. PMID:24464905

  19. Wnt Signalling Promotes Actin Dynamics during Axon Remodelling through the Actin-Binding Protein Eps8

    PubMed Central

    Salinas, Patricia C.

    2015-01-01

    Upon arrival at their synaptic targets, axons slow down their growth and extensively remodel before the assembly of presynaptic boutons. Wnt proteins are target-derived secreted factors that promote axonal remodelling and synaptic assembly. In the developing spinal cord, Wnts secreted by motor neurons promote axonal remodelling of NT-3 responsive dorsal root ganglia neurons. Axon remodelling induced by Wnts is characterised by growth cone pausing and enlargement, processes that depend on the re-organisation of microtubules. However, the contribution of the actin cytoskeleton has remained unexplored. Here, we demonstrate that Wnt3a regulates the actin cytoskeleton by rapidly inducing F-actin accumulation in growth cones from rodent DRG neurons through the scaffold protein Dishevelled-1 (Dvl1) and the serine-threonine kinase Gsk3β. Importantly, these changes in actin cytoskeleton occurs before enlargement of the growth cones is evident. Time-lapse imaging shows that Wnt3a increases lamellar protrusion and filopodia velocity. In addition, pharmacological inhibition of actin assembly demonstrates that Wnt3a increases actin dynamics. Through a yeast-two hybrid screen, we identified the actin-binding protein Eps8 as a direct interactor of Dvl1, a scaffold protein crucial for the Wnt signalling pathway. Gain of function of Eps8 mimics Wnt-mediated axon remodelling, whereas Eps8 silencing blocks the axon remodelling activity of Wnt3a. Importantly, blockade of the Dvl1-Eps8 interaction completely abolishes Wnt3a-mediated axonal remodelling. These findings demonstrate a novel role for Wnt-Dvl1 signalling through Eps8 in the regulation of axonal remodeling. PMID:26252776

  20. A Computational Study of the Effects of Syk Activity on B Cell Receptor Signaling Dynamics

    PubMed Central

    McGee, Reginald L.; Krisenko, Mariya O.; Geahlen, Robert L.; Rundell, Ann E.; Buzzard, Gregery T.

    2015-01-01

    The kinase Syk is intricately involved in early signaling events in B cells and is required for proper response when antigens bind to B cell receptors (BCRs). Experiments using an analog-sensitive version of Syk (Syk-AQL) have better elucidated its role, but have not completely characterized its behavior. We present a computational model for BCR signaling, using dynamical systems, which incorporates both wild-type Syk and Syk-AQL. Following the use of sensitivity analysis to identify significant reaction parameters, we screen for parameter vectors that produced graded responses to BCR stimulation as is observed experimentally. We demonstrate qualitative agreement between the model and dose response data for both mutant and wild-type kinases. Analysis of our model suggests that the level of NF-κB activation, which is reduced in Syk-AQL cells relative to wild-type, is more sensitive to small reductions in kinase activity than Erkp activation, which is essentially unchanged. Since this profile of high Erkp and reduced NF-κB is consistent with anergy, this implies that anergy is particularly sensitive to small changes in catalytic activity. Also, under a range of forward and reverse ligand binding rates, our model of Erkp and NF-κB activation displays a dependence on a power law affinity: the ratio of the forward rate to a non-unit power of the reverse rate. This dependence implies that B cells may respond to certain details of binding and unbinding rates for ligands rather than simple affinity alone. PMID:26525178

  1. Quantitative Analysis of Robustness of Dynamic Response and Signal Transfer in Insulin mediated PI3K/AKT Pathway

    PubMed Central

    Mathew, Shibin; Banerjee, Ipsita

    2014-01-01

    Robustness is a critical feature of signaling pathways ensuring signal propagation with high fidelity in the event of perturbations. Here we present a detailed quantitative analysis of robustness in insulin mediated PI3K/AKT pathway, a critical signaling pathway maintaining self-renewal in human embryonic stem cells. Using global sensitivity analysis, we identified robustness promoting mechanisms that ensure (1) maintenance of a first order or overshoot dynamics of self-renewal molecule, p-AKT and (2) robust transfer of signals from oscillatory insulin stimulus to p-AKT in the presence of noise. Our results indicate that negative feedback controls the robustness to most perturbations. Faithful transfer of signal from the stimulating ligand to p-AKT occurs even in the presence of noise, albeit with signal attenuation and high frequency cut-off. Negative feedback contributes to signal attenuation, while positive regulators upstream of PIP3 contribute to signal amplification. These results establish precise mechanisms to modulate self-renewal molecules like p-AKT. PMID:25506104

  2. Application of a novel multi-stage signal parameter estimator to high dynamic GPS receivers

    NASA Technical Reports Server (NTRS)

    Kumar, R.

    1990-01-01

    The performance of a novel multistage estimator when applied to the estimation of the position, velocity, and acceleration of high dynamic Global Positioning System (GPS) receivers is discussed. For the present application, a two-stage specialization of the more general estimation scheme is considered, wherein the first-stage algorithm is selected to be a modified least-squares algorithm operating upon the differential signal model and referred to as differential least-squares (DLS) and the second stage is simply an extended Kalman filter (EKF). In terms of the threshold on received carrier power-to-noise power spectral density ratio (CNR), when compared to the single-stage EKF algorithm, the DLS-EKF algorithm is about 1.5-2.0 dB better in terms of threshold and outperforms the crossproduct AFC (automatic frequency control) loop by 2-5 dB. For the case when data modulation is present, the proposed scheme provides an improvement of about 6 dB in terms of CNR compared to an earlier approximate MLE (maximum likelihood estimation) scheme. There are also very significant improvements in terms of other performance measures.

  3. Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans

    PubMed Central

    Kumar, Neeraj; Jagtap, Urmila; Verma, Sonia; Mukhopadhyay, Arnab

    2015-01-01

    Lowering insulin-IGF-1-like signalling (IIS) activates FOXO transcription factors (TF) to extend life span across species. To study the dynamics of FOXO chromatin occupancy under this condition in C. elegans, we report the first recruitment profile of endogenous DAF-16 and show that the response is conserved. DAF-16 predominantly acts as a transcriptional activator and binding within the 0.5 kb promoter-proximal region results in maximum induction of downstream targets that code for proteins involved in detoxification and longevity. Interestingly, genes that are activated under low IIS already have higher DAF-16 recruited to their promoters in WT. DAF-16 binds to variants of the FOXO consensus sequence in the promoter proximal regions of genes that are exclusively targeted during low IIS. We also define a set of ‘core’ direct targets, after comparing multiple studies, which tend to co-express and contribute robustly towards IIS-associated phenotypes. Additionally, we show that nuclear hormone receptor DAF-12 as well as zinc-finger TF EOR-1 may bind DNA in close proximity to DAF-16 and distinct TF classes that are direct targets of DAF-16 may be instrumental in regulating its indirect targets. Together, our study provides fundamental insights into the transcriptional biology of FOXO/DAF-16 and gene regulation downstream of the IIS pathway. PMID:26539642

  4. Investigating the allosteric reverse signalling of PARP inhibitors with microsecond molecular dynamic simulations and fluorescence anisotropy.

    PubMed

    Marchand, Jean-Rémy; Carotti, Andrea; Passeri, Daniela; Filipponi, Paolo; Liscio, Paride; Camaioni, Emidio; Pellicciari, Roberto; Gioiello, Antimo; Macchiarulo, Antonio

    2014-10-01

    The inhibition of the poly(ADP-ribose) polymerase (PARP) family members is a strategy pursued for the development of novel therapeutic agents in a range of diseases, including stroke, cardiac ischemia, cancer, inflammation and diabetes. Even though some PARP-1 inhibitors have advanced to clinical setting for cancer therapy, a great deal of attention is being devoted to understand the polypharmacology of current PARP inhibitors. Besides blocking the catalytic activity, recent works have shown that some PARP inhibitors exhibit a poisoning activity, by trapping the enzyme at damaged sites of DNA and forming cytotoxic complexes. In this study we have used microsecond molecular dynamics to study the allosteric reverse signalling that is at the basis of such an effect. We show that Olaparib, but not Veliparib and HYDAMTIQ, is able to induce a specific conformational drift of the WGR domain of PARP-1, which stabilizes PARP-1/DNA complex through the locking of several salt bridge interactions. Fluorescence anisotropy assays support such a mechanism, providing the first experimental evidence that HYDAMTIQ, a potent PARP inhibitor with neuroprotective properties, is less potent than Olaparib to trap PARP-1/DNA complex. PMID:25062913

  5. Modeling Signal Propagation Mechanisms and Ligand-Based Conformational Dynamics of the Hsp90 Molecular Chaperone Full-Length Dimer

    PubMed Central

    Morra, Giulia; Verkhivker, Gennady; Colombo, Giorgio

    2009-01-01

    Hsp90 is a molecular chaperone essential for protein folding and activation in normal homeostasis and stress response. ATP binding and hydrolysis facilitate Hsp90 conformational changes required for client activation. Hsp90 plays an important role in disease states, particularly in cancer, where chaperoning of the mutated and overexpressed oncoproteins is important for function. Recent studies have illuminated mechanisms related to the chaperone function. However, an atomic resolution view of Hsp90 conformational dynamics, determined by the presence of different binding partners, is critical to define communication pathways between remote residues in different domains intimately affecting the chaperone cycle. Here, we present a computational analysis of signal propagation and long-range communication pathways in Hsp90. We carried out molecular dynamics simulations of the full-length Hsp90 dimer, combined with essential dynamics, correlation analysis, and a signal propagation model. All-atom MD simulations with timescales of 70 ns have been performed for complexes with the natural substrates ATP and ADP and for the unliganded dimer. We elucidate the mechanisms of signal propagation and determine “hot spots” involved in interdomain communication pathways from the nucleotide-binding site to the C-terminal domain interface. A comprehensive computational analysis of the Hsp90 communication pathways and dynamics at atomic resolution has revealed the role of the nucleotide in effecting conformational changes, elucidating the mechanisms of signal propagation. Functionally important residues and secondary structure elements emerge as effective mediators of communication between the nucleotide-binding site and the C-terminal interface. Furthermore, we show that specific interdomain signal propagation pathways may be activated as a function of the ligand. Our results support a “conformational selection model” of the Hsp90 mechanism, whereby the protein may exist in a

  6. Negative feedback in the bone morphogenetic protein 4 (BMP4) synexpression group governs its dynamic signaling range and canalizes development

    PubMed Central

    Paulsen, Malte; Legewie, Stefan; Eils, Roland; Karaulanov, Emil; Niehrs, Christof

    2011-01-01

    What makes embryogenesis a robust and canalized process is an important question in developmental biology. A bone morphogenetic protein (BMP) morphogen gradient plays a key role in embryonic development, and we are beginning to understand how the self-regulating properties of its signaling circuitry ensure robust embryonic patterning. An unexplored question is why the BMP signaling circuit is organized as a modular synexpression group, with a prevalence of feedback inhibitors. Here, we provide evidence from direct experimentation and mathematical modeling that the synexpressed feedback inhibitors BAMBI, SMAD6, and SMAD7 (i) expand the dynamic BMP signaling range essential for proper embryonic patterning and (ii) reduce interindividual phenotypic and molecular variability in Xenopus embryos. Thereby, negative feedback linearizes signaling responses and confers robust patterning, thus promoting canalized development. The presence of negative feedback inhibitors in other growth factor synexpression groups suggests that these properties may constitute a general principle. PMID:21633009

  7. Dynamic Modeling and Analysis of the Cross-Talk between Insulin/AKT and MAPK/ERK Signaling Pathways

    PubMed Central

    Arkun, Yaman

    2016-01-01

    Feedback loops play a key role in the regulation of the complex interactions in signal transduction networks. By studying the network of interactions among the biomolecules present in signaling pathways at the systems level, it is possible to understand how the biological functions are regulated and how the diseases emerge from their deregulations. This paper identifies the key feedback loops involved in the cross-talk among the insulin-AKT and MAPK/ERK signaling pathways. We developed a mathematical model that can be used to study the steady-state and dynamic behavior of the interactions among these two important signaling pathways. Modeling analysis and simulation case studies identify the key interaction parameters and the feedback loops that determine the normal and disease phenotypes. PMID:26930065

  8. Dynamic NF-κB and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation

    PubMed Central

    Ankers, John M; Awais, Raheela; Jones, Nicholas A; Boyd, James; Ryan, Sheila; Adamson, Antony D; Harper, Claire V; Bridge, Lloyd; Spiller, David G; Jackson, Dean A; Paszek, Pawel; Sée, Violaine; White, Michael RH

    2016-01-01

    Dynamic cellular systems reprogram gene expression to ensure appropriate cellular fate responses to specific extracellular cues. Here we demonstrate that the dynamics of Nuclear Factor kappa B (NF-κB) signalling and the cell cycle are prioritised differently depending on the timing of an inflammatory signal. Using iterative experimental and computational analyses, we show physical and functional interactions between NF-κB and the E2 Factor 1 (E2F-1) and E2 Factor 4 (E2F-4) cell cycle regulators. These interactions modulate the NF-κB response. In S-phase, the NF-κB response was delayed or repressed, while cell cycle progression was unimpeded. By contrast, activation of NF-κB at the G1/S boundary resulted in a longer cell cycle and more synchronous initial NF-κB responses between cells. These data identify new mechanisms by which the cellular response to stress is differentially controlled at different stages of the cell cycle. DOI: http://dx.doi.org/10.7554/eLife.10473.001 PMID:27185527

  9. Dynamic Response and Signal to Noise Ratio Investigation of NIR-FBG Dynamic Sensing System for Monitoring Thin- walled Composite Plate

    NASA Astrophysics Data System (ADS)

    Hafizi, Z. M.; Epaarachchi, J.

    2015-12-01

    Optical fiber systems for dynamic response measurement become an attractive study nowadays especially in the field of Structural Health Monitoring (SHM). This work presents the investigation of an optical fiber sensor system utilizing Near Infra-Red Fiber Bragg Grating (NIR-FBG) sensor for SHM of a thin-walled composite structure. In this study, a comparison between the experimental result and simulation study using finite element analysis has been presented. By comparing both results, the FBG dynamic sensing system was shown to have an excellent capability in acquiring dynamic response due to flexural wave propagations. In the meantime, a signal to noise ratio (SNR) study was also performed to several FBG dynamic sensor systems; particularly to see the comparison between NIR-FBG sensor and 1550 nm FBG sensor. Furthermore, with a proper configuration, an NIR-FBG system was proved to have better performance than the 1550 nm based FBG sensor.

  10. SU-E-J-261: Statistical Analysis and Chaotic Dynamics of Respiratory Signal of Patients in BodyFix

    SciTech Connect

    Michalski, D; Huq, M; Bednarz, G; Lalonde, R; Yang, Y; Heron, D

    2014-06-01

    Purpose: To quantify respiratory signal of patients in BodyFix undergoing 4DCT scan with and without immobilization cover. Methods: 20 pairs of respiratory tracks recorded with RPM system during 4DCT scan were analyzed. Descriptive statistic was applied to selected parameters of exhale-inhale decomposition. Standardized signals were used with the delay method to build orbits in embedded space. Nonlinear behavior was tested with surrogate data. Sample entropy SE, Lempel-Ziv complexity LZC and the largest Lyapunov exponents LLE were compared. Results: Statistical tests show difference between scans for inspiration time and its variability, which is bigger for scans without cover. The same is for variability of the end of exhalation and inhalation. Other parameters fail to show the difference. For both scans respiratory signals show determinism and nonlinear stationarity. Statistical test on surrogate data reveals their nonlinearity. LLEs show signals chaotic nature and its correlation with breathing period and its embedding delay time. SE, LZC and LLE measure respiratory signal complexity. Nonlinear characteristics do not differ between scans. Conclusion: Contrary to expectation cover applied to patients in BodyFix appears to have limited effect on signal parameters. Analysis based on trajectories of delay vectors shows respiratory system nonlinear character and its sensitive dependence on initial conditions. Reproducibility of respiratory signal can be evaluated with measures of signal complexity and its predictability window. Longer respiratory period is conducive for signal reproducibility as shown by these gauges. Statistical independence of the exhale and inhale times is also supported by the magnitude of LLE. The nonlinear parameters seem more appropriate to gauge respiratory signal complexity since its deterministic chaotic nature. It contrasts with measures based on harmonic analysis that are blind for nonlinear features. Dynamics of breathing, so crucial for

  11. Photonics-assistant spectra shaping of ultra-wideband signals for dynamic spectrum access in cognitive network

    NASA Astrophysics Data System (ADS)

    Zheng, Jianyu; Zhu, Ninghua; Wang, Lixian; Wang, Hui; Du, Yuanxin; Liu, Jianguo

    2012-11-01

    The dynamic control for the spectra of the Ultra-wideband (UWB) signals, which is the key for implementing the dynamic spectrum access in the cognitive radio, is still a challenge due to the limited processing speed of the electronic devices. In this paper, we have summarized our recent work about controlling the spectrum shape of the UWB signals in optical domain, in addition to reviewing the other groups' related research work. The experiment setups and results based on nonlinear dynamics of the optoelectronic oscillator and transfer response of the phase or polarization-to-intensity convertor will be described in detail respectively, in which the controllable frequency suppress for the optical UWB signals at specific frequency positions were implemented. Particularly, the UWB pulse with the special shape, which corresponds to the 5-GHz band-rejection in frequency domain, was generated in order to avoid the interference between UWB and Wireless Fidelity system in practice. In addition, the UWB signals whose center frequency could be continuously tuned and converted up to the frequency range of millimeter wave were generated by utilizing the polarization modulator based optical switch. The areas for future development and the challenge of implementing these techniques for the applications in practice will also be discussed.

  12. An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells

    PubMed Central

    Turner, David A.; Trott, Jamie; Hayward, Penelope; Rué, Pau; Martinez Arias, Alfonso

    2014-01-01

    ABSTRACT Embryonic Stem cells derived from the epiblast tissue of the mammalian blastocyst retain the capability to differentiate into any adult cell type and are able to self-renew indefinitely under appropriate culture conditions. Despite the large amount of knowledge that we have accumulated to date about the regulation and control of self-renewal, efficient directed differentiation into specific tissues remains elusive. In this work, we have analysed in a systematic manner the interaction between the dynamics of loss of pluripotency and Activin/Nodal, BMP4 and Wnt signalling in fate assignment during the early stages of differentiation of mouse ES cells in culture. During the initial period of differentiation, cells exit from pluripotency and enter an Epi-like state. Following this transient stage, and under the influence of Activin/Nodal and BMP signalling, cells face a fate choice between differentiating into neuroectoderm and contributing to Primitive Streak fates. We find that Wnt signalling does not suppress neural development as previously thought and that it aids both fates in a context dependent manner. Our results suggest that as cells exit pluripotency they are endowed with a primary neuroectodermal fate and that the potency to become endomesodermal rises with time. We suggest that this situation translates into a “race for fates” in which the neuroectodermal fate has an advantage. PMID:24950969

  13. Signal enhancement in optical projection tomography via virtual high dynamic range imaging of single exposure

    NASA Astrophysics Data System (ADS)

    Yang, Yujie; Dong, Di; Shi, Liangliang; Wang, Jun; Yang, Xin; Tian, Jie

    2015-03-01

    Optical projection tomography (OPT) is a mesoscopic scale optical imaging technique for specimens between 1mm and 10mm. OPT has been proven to be immensely useful in a wide variety of biological applications, such as developmental biology and pathology, but its shortcomings in imaging specimens containing widely differing contrast elements are obvious. The longer exposure for high intensity tissues may lead to over saturation of other areas, whereas a relatively short exposure may cause similarity with surrounding background. In this paper, we propose an approach to make a trade-off between capturing weak signals and revealing more details for OPT imaging. This approach consists of three steps. Firstly, the specimens are merely scanned in 360 degrees above a normal exposure but non-overexposure to acquire the projection data. This reduces the photo bleaching and pre-registration computation compared with multiple different exposures in conventional high dynamic range (HDR) imaging method. Secondly, three virtual channels are produced for each projection image based on the histogram distribution to simulate the low, normal and high exposure images used in the traditional HDR technology in photography. Finally, each virtual channel is normalized to the full gray scale range and three channels are recombined into one image using weighting coefficients optimized by a standard eigen-decomposition method. After applying our approach on the projection data, filtered back projection (FBP) algorithm is carried out for 3-dimentional reconstruction. The neonatal wild-type mouse paw has been scanned to verify this approach. Results demonstrated the effectiveness of the proposed approach.

  14. Role of Structural Dynamics at the Receptor G Protein Interface for Signal Transduction

    PubMed Central

    Rose, Alexander S.; Zachariae, Ulrich; Grubmüller, Helmut; Hofmann, Klaus Peter; Scheerer, Patrick; Hildebrand, Peter W.

    2015-01-01

    GPCRs catalyze GDP/GTP exchange in the α-subunit of heterotrimeric G proteins (Gαßγ) through displacement of the Gα C-terminal α5 helix, which directly connects the interface of the active receptor (R*) to the nucleotide binding pocket of G. Hydrogen–deuterium exchange mass spectrometry and kinetic analysis of R* catalysed G protein activation have suggested that displacement of α5 starts from an intermediate GDP bound complex (R*•GGDP). To elucidate the structural basis of receptor-catalysed displacement of α5, we modelled the structure of R*•GGDP. A flexible docking protocol yielded an intermediate R*•GGDP complex, with a similar overall arrangement as in the X-ray structure of the nucleotide free complex (R*•Gempty), however with the α5 C-terminus (GαCT) forming different polar contacts with R*. Starting molecular dynamics simulations of GαCT bound to R* in the intermediate position, we observe a screw-like motion, which restores the specific interactions of α5 with R* in R*•Gempty. The observed rotation of α5 by 60° is in line with experimental data. Reformation of hydrogen bonds, water expulsion and formation of hydrophobic interactions are driving forces of the α5 displacement. We conclude that the identified interactions between R* and G protein define a structural framework in which the α5 displacement promotes direct transmission of the signal from R* to the GDP binding pocket. PMID:26606751

  15. Role of Structural Dynamics at the Receptor G Protein Interface for Signal Transduction.

    PubMed

    Rose, Alexander S; Zachariae, Ulrich; Grubmüller, Helmut; Hofmann, Klaus Peter; Scheerer, Patrick; Hildebrand, Peter W

    2015-01-01

    GPCRs catalyze GDP/GTP exchange in the α-subunit of heterotrimeric G proteins (Gαßγ) through displacement of the Gα C-terminal α5 helix, which directly connects the interface of the active receptor (R*) to the nucleotide binding pocket of G. Hydrogen-deuterium exchange mass spectrometry and kinetic analysis of R* catalysed G protein activation have suggested that displacement of α5 starts from an intermediate GDP bound complex (R*•GGDP). To elucidate the structural basis of receptor-catalysed displacement of α5, we modelled the structure of R*•GGDP. A flexible docking protocol yielded an intermediate R*•GGDP complex, with a similar overall arrangement as in the X-ray structure of the nucleotide free complex (R*•Gempty), however with the α5 C-terminus (GαCT) forming different polar contacts with R*. Starting molecular dynamics simulations of GαCT bound to R* in the intermediate position, we observe a screw-like motion, which restores the specific interactions of α5 with R* in R*•Gempty. The observed rotation of α5 by 60° is in line with experimental data. Reformation of hydrogen bonds, water expulsion and formation of hydrophobic interactions are driving forces of the α5 displacement. We conclude that the identified interactions between R* and G protein define a structural framework in which the α5 displacement promotes direct transmission of the signal from R* to the GDP binding pocket. PMID:26606751

  16. Common language or Tower of Babel? On the evolutionary dynamics of signals and their meanings.

    PubMed

    van Baalen, Minus; Jansen, Vincent A A

    2003-01-01

    We investigate how the evolution of communication strategies affects signal credibility when there is common interest as well as a conflict between communicating individuals. Taking alarm calls as an example, we show that if the temptation to cheat is low, a single signal is used in the population. If the temptation increases cheaters will erode the credibility of a signal, and an honest mutant using a different signal ('a private code') will be very successful until this, in turn, is cracked by cheaters. In such a system, signal use fluctuates in time and space and hence the meaning of a given signal is not constant. When the temptation to cheat is too large, no honest communication can maintain itself in a Tower of Babel of many signals. We discuss our analysis in the light of the Green Beard mechanism for the evolution of altruism. PMID:12590773

  17. Dynamic full field optical coherence tomography: subcellular metabolic contrast revealed in tissues by interferometric signals temporal analysis

    PubMed Central

    Apelian, Clement; Harms, Fabrice; Thouvenin, Olivier; Boccara, A. Claude

    2016-01-01

    We developed a new endogenous approach to reveal subcellular metabolic contrast in fresh ex vivo tissues taking advantage of the time dependence of the full field optical coherence tomography interferometric signals. This method reveals signals linked with local activity of the endogenous scattering elements which can reveal cells where other OCT-based techniques fail or need exogenous contrast agents. We benefit from the micrometric transverse resolution of full field OCT to image intracellular features. We used this time dependence to identify different dynamics at the millisecond scale on a wide range of organs in normal or pathological conditions. PMID:27446672

  18. How Intrinsic Molecular Dynamics Control Intramolecular Communication in Signal Transducers and Activators of Transcription Factor STAT5

    PubMed Central

    Langenfeld, Florent; Guarracino, Yann; Arock, Michel; Trouvé, Alain; Tchertanov, Luba

    2015-01-01

    Signal Transducer and Activator of Transcription STAT5 is a key mediator of cell proliferation, differentiation and survival. While STAT5 activity is tightly regulated in normal cells, its constitutive activation directly contributes to oncogenesis and is associated with a broad range of hematological and solid tumor cancers. Therefore the development of compounds able to modulate pathogenic activation of this protein is a very challenging endeavor. A crucial step of drug design is the understanding of the protein conformational features and the definition of putative binding site(s) for such modulators. Currently, there is no structural data available for human STAT5 and our study is the first footprint towards the description of structure and dynamics of this protein. We investigated structural and dynamical features of the two STAT5 isoforms, STAT5a and STAT5b, taken into account their phosphorylation status. The study was based on the exploration of molecular dynamics simulations by different analytical methods. Despite the overall folding similarity of STAT5 proteins, the MD conformations display specific structural and dynamical features for each protein, indicating first, sequence-encoded structural properties and second, phosphorylation-induced effects which contribute to local and long-distance structural rearrangements interpreted as allosteric event. Further examination of the dynamical coupling between distant sites provides evidence for alternative profiles of the communication pathways inside and between the STAT5 domains. These results add a new insight to the understanding of the crucial role of intrinsic molecular dynamics in mediating intramolecular signaling in STAT5. Two pockets, localized in close proximity to the phosphotyrosine-binding site and adjacent to the channel for communication pathways across STAT5, may constitute valid targets to develop inhibitors able to modulate the function-related communication properties of this signaling

  19. Notes on simulating two-dimensional Raman and terahertz-Raman signals with a full molecular dynamics simulation approach

    PubMed Central

    Ito, Hironobu; Jo, Ju-Yeon; Tanimura, Yoshitaka

    2015-01-01

    Recent developments in two-dimensional (2D) THz-Raman and 2D Raman spectroscopies have created the possibility for quantitatively investigating the role of many dynamic and structural aspects of the molecular system. We explain the significant points for properly simulating 2D vibrational spectroscopic studies of intermolecular modes using the full molecular dynamics approach, in particular, regarding the system size, the treatment of the thermostat, and inclusion of an Ewald summation for the induced polarizability. Moreover, using the simulation results for water employing various polarization functions, we elucidate the roles of permanent and induced optical properties in determining the 2D profiles of the signal. PMID:26798823

  20. Gene-centric meta-analyses of 108 912 individuals confirm known body mass index loci and reveal three novel signals.

    PubMed

    Guo, Yiran; Lanktree, Matthew B; Taylor, Kira C; Hakonarson, Hakon; Lange, Leslie A; Keating, Brendan J

    2013-01-01

    Recent genetic association studies have made progress in uncovering components of the genetic architecture of the body mass index (BMI). We used the ITMAT-Broad-Candidate Gene Association Resource (CARe) (IBC) array comprising up to 49 320 single nucleotide polymorphisms (SNPs) across ~2100 metabolic and cardiovascular-related loci to genotype up to 108 912 individuals of European ancestry (EA), African-Americans, Hispanics and East Asians, from 46 studies, to provide additional insight into SNPs underpinning BMI. We used a five-phase study design: Phase I focused on meta-analysis of EA studies providing individual level genotype data; Phase II performed a replication of cohorts providing summary level EA data; Phase III meta-analyzed results from the first two phases; associated SNPs from Phase III were used for replication in Phase IV; finally in Phase V, a multi-ethnic meta-analysis of all samples from four ethnicities was performed. At an array-wide significance (P < 2.40E-06), we identify novel BMI associations in loci translocase of outer mitochondrial membrane 40 homolog (yeast) - apolipoprotein E - apolipoprotein C-I (TOMM40-APOE-APOC1) (rs2075650, P = 2.95E-10), sterol regulatory element binding transcription factor 2 (SREBF2, rs5996074, P = 9.43E-07) and neurotrophic tyrosine kinase, receptor, type 2 [NTRK2, a brain-derived neurotrophic factor (BDNF) receptor gene, rs1211166, P = 1.04E-06] in the Phase IV meta-analysis. Of 10 loci with previous evidence for BMI association represented on the IBC array, eight were replicated, with the remaining two showing nominal significance. Conditional analyses revealed two independent BMI-associated signals in BDNF and melanocortin 4 receptor (MC4R) regions. Of the 11 array-wide significant SNPs, three are associated with gene expression levels in both primary B-cells and monocytes; with rs4788099 in SH2B adaptor protein 1 (SH2B1) notably being associated with the expression of multiple genes in cis. These multi

  1. Microprocessor-based multichannel flutter monitor using dynamic strain gage signals

    NASA Technical Reports Server (NTRS)

    Smalley, R. R.

    1976-01-01

    Two microprocessor-based multichannel monitors for monitoring strain gage signals during aerodynamic instability (flutter) testing in production type turbojet engines were described. One system monitors strain gage signals in the time domain and gives an output indication whenever the signal amplitude of any gage exceeds a pre-set alarm or abort level for that particular gage. The second system monitors the strain gage signals in the frequency domain and therefore is able to use both the amplitude and frequency information. Thus, an alarm signal is given whenever the spectral content of the strain gage signal exceeds, at any point, its corresponding amplitude vs. frequency limit profiles. Each system design is described with details on design trade-offs, hardware, software, and operating experience.

  2. Potential dynamics of the human striate cortex cerebrum realistic neural network under the influence of an external signal

    NASA Astrophysics Data System (ADS)

    Melnikov, Leonid A.; Novosselova, Anna V.; Blinova, Nadejda V.; Vinitsky, Sergey I.; Serov, Vladislav V.; Bakutkin, Valery V.; Camenskich, T. G.; Guileva, E. V.

    2000-03-01

    In this work the numerical investigations of a potential dynamics of a neural network as the non-linear system and dynamics of the visual nerve which connect the eye retina receptors with the striate cortex cerebrum as the answer to the through-skin excitement of the eye retina by the electrical signal were realized. The visual evoked potential is the answer and characterizes the human brain state over the structures retina state and the conduction of the visual nerve fibers. The results of these investigations were presented. Specific features of the neural network, such as the excitation and depression, we took into account too. The discussion about the model parameters, used at the time of the numerical investigation, was made. The comparative analysis of the retina potential data and the data of the external signal filing by the brain hemicerebrum visual centers was made too.

  3. Quantifying the complexity of excised larynx vibrations from high-speed imaging using spatiotemporal and nonlinear dynamic analyses

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Jiang, Jack J.; Tao, Chao; Bieging, Erik; MacCallum, Julia K.

    2007-12-01

    In this paper, we investigate the biomechanical applications of spatiotemporal analysis and nonlinear dynamic analysis to quantitatively describe regular and irregular vibrations of twelve excised larynges from high-speed image recordings. Regular vibrations show simple spatial symmetry, temporal periodicity, and discrete frequency spectra, while irregular vibrations show complex spatiotemporal plots, aperiodic time series, and broadband spectra. Furthermore, the global entropy and correlation length from spatiotemporal analysis and the correlation dimension from nonlinear dynamic analysis reveal a statistical difference between regular and irregular vibrations. In comparison with regular vibrations, the global entropy and correlation dimension of irregular vibrations are statistically higher, while the correlation length is significantly lower. These findings show that spatiotemporal analysis and nonlinear dynamic analysis are capable of describing the complex dynamics of vocal fold vibrations from high-speed imaging and may potentially be helpful for understanding disordered behaviors in biomedical laryngeal systems.

  4. Understanding THz and IR signals beneath time-resolved fluorescence from excited-state ab initio dynamics.

    PubMed

    Petrone, Alessio; Donati, Greta; Caruso, Pasquale; Rega, Nadia

    2014-10-22

    The detailed interpretation of time-resolved spectroscopic signals in terms of the molecular rearrangement during a photoreaction or a photophysical event is one of the most important challenges of both experimental and theoretical chemistry. Here we simulate a time-resolved fluorescence spectrum of a dye in aqueous solution, the N-methyl-6-oxyquinolinium betaine, and analyze it in terms of far IR and THz frequency contributions, providing a direct connection to specific molecular motions. To obtain this result, we build up an innovative and general approach based on excited state ab-initio molecular dynamics and a wavelet-based time-dependent frequency analysis of nonstationary signals. We obtain a nice agreement with key parameters of the solvent dynamics, such as the total Stokes shift and the Stokes shift relaxation times. As an important finding, we observe a strong change of specific solute-solvent interactions upon the electronic excitation, with the migration of about 1.5 water molecules from the first solvation shell toward the bulk. In spite of this event, the Stokes shift dynamics is ruled by collective solvent motions in the THz and far IR, which guide and modulate the strong rearrangement of the dye microsolvation. By the relaxation of THz and IR contributions to the emission signal, we can follow and understand in detail the molecularity of the process. The protocol presented here is, in principle, transferable to other time-resolved spectroscopic techniques. PMID:25243826

  5. SYSTEMATICS OF DYNAMICAL MASS EJECTION, NUCLEOSYNTHESIS, AND RADIOACTIVELY POWERED ELECTROMAGNETIC SIGNALS FROM NEUTRON-STAR MERGERS

    SciTech Connect

    Bauswein, A.; Janka, H.-T.; Goriely, S.

    2013-08-10

    We investigate systematically the dynamical mass ejection, r-process nucleosynthesis, and properties of electromagnetic counterparts of neutron-star (NS) mergers in dependence on the uncertain properties of the nuclear equation of state (EOS) by employing 40 representative, microphysical high-density EOSs in relativistic, hydrodynamical simulations. The crucial parameter determining the ejecta mass is the radius R{sub 1.35} of a 1.35 M{sub Sun} NS. NSs with smaller R{sub 1.35} (''soft'' EOS) eject systematically higher masses. These range from {approx}10{sup -3} M{sub Sun} to {approx}10{sup -2} M{sub Sun} for 1.35-1.35 M{sub Sun} binaries and from {approx}5 Multiplication-Sign 10{sup -3} M{sub Sun} to {approx}2 Multiplication-Sign 10{sup -2} M{sub Sun} for 1.2-1.5 M{sub Sun} systems (with kinetic energies between {approx}5 Multiplication-Sign 10{sup 49} erg and 10{sup 51} erg). Correspondingly, the bolometric peak luminosities of the optical transients of symmetric (asymmetric) mergers vary between 3 Multiplication-Sign 10{sup 41} erg s{sup -1} and 14 Multiplication-Sign 10{sup 41} erg s{sup -1} (9 Multiplication-Sign 10{sup 41} erg s{sup -1} and 14.5 Multiplication-Sign 10{sup 41} erg s{sup -1}) on timescales between {approx}2 hr and {approx}12 hr. If these signals with absolute bolometric magnitudes from -15.0 to -16.7 are measured, the tight correlation of their properties with those of the merging NSs might provide valuable constraints on the high-density EOS. The r-process nucleosynthesis exhibits a remarkable robustness independent of the EOS, producing a nearly solar abundance pattern above mass number 130. By the r-process content of the Galaxy and the average production per event the Galactic merger rate is limited to 4 Multiplication-Sign 10{sup -5} yr{sup -1} (4 Multiplication-Sign 10{sup -4} yr{sup -1}) for a soft (stiff) NS EOS, if NS mergers are the main source of heavy r-nuclei. The production ratio of radioactive {sup 232}Th to {sup 238}U attains a

  6. Systematics of Dynamical Mass Ejection, Nucleosynthesis, and Radioactively Powered Electromagnetic Signals from Neutron-star Mergers

    NASA Astrophysics Data System (ADS)

    Bauswein, A.; Goriely, S.; Janka, H.-T.

    2013-08-01

    We investigate systematically the dynamical mass ejection, r-process nucleosynthesis, and properties of electromagnetic counterparts of neutron-star (NS) mergers in dependence on the uncertain properties of the nuclear equation of state (EOS) by employing 40 representative, microphysical high-density EOSs in relativistic, hydrodynamical simulations. The crucial parameter determining the ejecta mass is the radius R 1.35 of a 1.35 M ⊙ NS. NSs with smaller R 1.35 ("soft" EOS) eject systematically higher masses. These range from ~10-3 M ⊙ to ~10-2 M ⊙ for 1.35-1.35 M ⊙ binaries and from ~5 × 10-3 M ⊙ to ~2 × 10-2 M ⊙ for 1.2-1.5 M ⊙ systems (with kinetic energies between ~5 × 1049 erg and 1051 erg). Correspondingly, the bolometric peak luminosities of the optical transients of symmetric (asymmetric) mergers vary between 3 × 1041 erg s-1 and 14 × 1041 erg s-1 (9 × 1041 erg s-1 and 14.5 × 1041 erg s-1) on timescales between ~2 hr and ~12 hr. If these signals with absolute bolometric magnitudes from -15.0 to -16.7 are measured, the tight correlation of their properties with those of the merging NSs might provide valuable constraints on the high-density EOS. The r-process nucleosynthesis exhibits a remarkable robustness independent of the EOS, producing a nearly solar abundance pattern above mass number 130. By the r-process content of the Galaxy and the average production per event the Galactic merger rate is limited to 4 × 10-5 yr-1 (4 × 10-4 yr-1) for a soft (stiff) NS EOS, if NS mergers are the main source of heavy r-nuclei. The production ratio of radioactive 232Th to 238U attains a stable value of 1.64-1.67, which does not exclude NS mergers as potential sources of heavy r-material in the most metal-poor stars.

  7. Dopamine Dynamics and Signaling in Drosophila: An Overview of Genes, Drugs and Behavioral Paradigms

    PubMed Central

    Yamamoto, Shinya; Seto, Elaine S.

    2014-01-01

    Changes in dopamine (DA) signaling have been implicated in a number of human neurologic and psychiatric disorders. Similarly, defects in DA signaling in the fruit fly, Drosophila melanogaster, have also been associated with several behavioral defects. As most genes involved in DA synthesis, transport, secretion, and signaling are conserved between species, Drosophila is a powerful genetic model organism to study the regulation of DA signaling in vivo. In this review, we will provide an overview of the genes and drugs that regulate DA biology in Drosophila. Furthermore, we will discuss the behavioral paradigms that are regulated by DA signaling in flies. By analyzing the genes and neuronal circuits that govern such behaviors using sophisticated genetic, pharmacologic, electrophysiologic, and imaging approaches in Drosophila, we will likely gain a better understanding about how this neuromodulator regulates motor tasks and cognition in humans. PMID:24770636

  8. A New Inertial Aid Method for High Dynamic Compass Signal Tracking Based on a Nonlinear Tracking Differentiator

    PubMed Central

    Guo, Yao; Wu, Wenqi; Tang, Kanghua

    2012-01-01

    In Compass/INS integrated navigation systems, feedback inertial navigation solutions to baseband tracking loops may eliminate receiver dynamic effects, and effectively improve the tracking accuracy and sensitivity. In the conventional inertially-aided tracking loop, the satellite-receiver line-of-sight velocity is used directly to adjust local carrier frequency. However, if the inertial solution drifts, the phase tracking error will be enlarged. By using Kalman filter based carrier phase tracking loop, this paper introduces a new inertial aid method, in which the line-of-sight jerk obtained from inertial acceleration by a nonlinear tracking differentiator is used to adjust relevant parameters of the Kalman filter's process noise matrix. Validation is achieved through high dynamic Compass B3 signal with line-of-sight jerk of 10 g/s collected by a GNSS simulator. Experimental results indicate that the new inertial aid method proposed in this paper is free of the impact of the receiver dynamic and inertial errors. Therefore, when the integrated navigation system is starting or re-tracking after losing lock, the inertial error is absent from the navigation solution correction that induces large drift, and the new aid method proposed in this paper can track highly dynamic signals. PMID:22969365

  9. SRM Internal Flow Tests and Computational Fluid Dynamic Analysis. Volume 2; CFD RSRM Full-Scale Analyses

    NASA Technical Reports Server (NTRS)

    2001-01-01

    This document presents the full-scale analyses of the CFD RSRM. The RSRM model was developed with a 20 second burn time. The following are presented as part of the full-scale analyses: (1) RSRM embedded inclusion analysis; (2) RSRM igniter nozzle design analysis; (3) Nozzle Joint 4 erosion anomaly; (4) RSRM full motor port slag accumulation analysis; (5) RSRM motor analysis of two-phase flow in the aft segment/submerged nozzle region; (6) Completion of 3-D Analysis of the hot air nozzle manifold; (7) Bates Motor distributed combustion test case; and (8) Three Dimensional Polysulfide Bump Analysis.

  10. Efficient detection and signal parameter estimation with applications to high dynamic GPS receivers

    NASA Technical Reports Server (NTRS)

    Kumar, R.

    1988-01-01

    A novel technique for simultaneously detecting data and estimating the parameters of a received carrier signal phase modulated by unknown data and experiencing very high Doppler, Doppler rate, etc. is discussed. Such a situation arises, for example, in the case of Global Positioning Systems (DPS) where the signal parameters are directly related to the position, velocity and acceleration of the GPS receiver. The proposed scheme is based upon first estimating the received signal local (data dependent) parameters over two consecutive bit periods, followed by the detection of a possible jump in these parameters. The presence of a detected jump signifies a data transition which is then removed from the received signal. This effectively demodulated signal is then processed to provide the estimates of global (data independent) parameters of the signal related to the position, velocity, etc. of the receiver. One of the key features of the proposed algorithm is the introduction of two different schemes which can provide an improvement of up to 3 dB over the conventional implementation of Kalman filter as applied to phase and frequency estimation, under low to medium signal-to-noise ratio conditions.

  11. Dynamics of a Definition: A Framework to Analyse Student Construction of the Concept of Solution to a Differential Equation

    ERIC Educational Resources Information Center

    Raychaudhuri, Debasree

    2008-01-01

    In this note we develop a framework that makes explicit the inherent dynamic structure of certain mathematical definitions by means of the four facets of context-entity-process-object. These facets and their interrelations are then used to capture and interpret specific aspects of student constructions of the concept of solution to first order…

  12. Single-Cell Phosphoproteomics Resolves Adaptive Signaling Dynamics and Informs Targeted Combination Therapy in Glioblastoma.

    PubMed

    Wei, Wei; Shin, Young Shik; Xue, Min; Matsutani, Tomoo; Masui, Kenta; Yang, Huijun; Ikegami, Shiro; Gu, Yuchao; Herrmann, Ken; Johnson, Dazy; Ding, Xiangming; Hwang, Kiwook; Kim, Jungwoo; Zhou, Jian; Su, Yapeng; Li, Xinmin; Bonetti, Bruno; Chopra, Rajesh; James, C David; Cavenee, Webster K; Cloughesy, Timothy F; Mischel, Paul S; Heath, James R; Gini, Beatrice

    2016-04-11

    Intratumoral heterogeneity of signaling networks may contribute to targeted cancer therapy resistance, including in the highly lethal brain cancer glioblastoma (GBM). We performed single-cell phosphoproteomics on a patient-derived in vivo GBM model of mTOR kinase inhibitor resistance and coupled it to an analytical approach for detecting changes in signaling coordination. Alterations in the protein signaling coordination were resolved as early as 2.5 days after treatment, anticipating drug resistance long before it was clinically manifest. Combination therapies were identified that resulted in complete and sustained tumor suppression in vivo. This approach may identify actionable alterations in signal coordination that underlie adaptive resistance, which can be suppressed through combination drug therapy, including non-obvious drug combinations. PMID:27070703

  13. Numerical insight into the seismic behavior of eight masonry towers in Northern Italy: FE pushover vs non-linear dynamic analyses

    NASA Astrophysics Data System (ADS)

    Milani, Gabriele; Valente, Marco

    2015-12-01

    This study presents some FE results regarding the behavior under horizontal loads of eight existing masonry towers located in the North-East of Italy. The towers, albeit unique for geometric and architectural features, show some affinities which justify a comparative analysis, as for instance the location and the similar masonry material. Their structural behavior under horizontal loads is therefore influenced by geometrical issues, such as slenderness, walls thickness, perforations, irregularities, presence of internal vaults, etc., all features which may be responsible for a peculiar output. The geometry of the towers is deduced from both existing available documentation and in-situ surveys. On the basis of such geometrical data, a detailed 3D realistic mesh is conceived, with a point by point characterization of each single geometric element. The FE models are analysed under seismic loads acting along geometric axes of the plan section, both under non-linear static (pushover) and non-linear dynamic excitation assumptions. A damage-plasticity material model exhibiting softening in both tension and compression, already available in the commercial code Abaqus, is used for masonry. Pushover analyses are performed with both G1 and G2 horizontal loads distribution, according to Italian code requirements, along X+/- and Y+/- directions. Non-linear dynamic analyses are performed along both X and Y directions with a real accelerogram scaled to different peak ground accelerations. Some few results are presented in this paper. It is found that the results obtained with pushover analyses reasonably well fit expensive non-linear dynamic simulations, with a slightly less conservative trend.

  14. Numerical insight into the seismic behavior of eight masonry towers in Northern Italy: FE pushover vs non-linear dynamic analyses

    SciTech Connect

    Milani, Gabriele E-mail: gabriele.milani@polimi.it; Valente, Marco

    2015-12-31

    This study presents some FE results regarding the behavior under horizontal loads of eight existing masonry towers located in the North-East of Italy. The towers, albeit unique for geometric and architectural features, show some affinities which justify a comparative analysis, as for instance the location and the similar masonry material. Their structural behavior under horizontal loads is therefore influenced by geometrical issues, such as slenderness, walls thickness, perforations, irregularities, presence of internal vaults, etc., all features which may be responsible for a peculiar output. The geometry of the towers is deduced from both existing available documentation and in-situ surveys. On the basis of such geometrical data, a detailed 3D realistic mesh is conceived, with a point by point characterization of each single geometric element. The FE models are analysed under seismic loads acting along geometric axes of the plan section, both under non-linear static (pushover) and non-linear dynamic excitation assumptions. A damage-plasticity material model exhibiting softening in both tension and compression, already available in the commercial code Abaqus, is used for masonry. Pushover analyses are performed with both G1 and G2 horizontal loads distribution, according to Italian code requirements, along X+/− and Y+/− directions. Non-linear dynamic analyses are performed along both X and Y directions with a real accelerogram scaled to different peak ground accelerations. Some few results are presented in this paper. It is found that the results obtained with pushover analyses reasonably well fit expensive non-linear dynamic simulations, with a slightly less conservative trend.

  15. Risks of multimodal signaling: bat predators attend to dynamic motion in frog sexual displays.

    PubMed

    Halfwerk, Wouter; Dixon, Marjorie M; Ottens, Kristina J; Taylor, Ryan C; Ryan, Michael J; Page, Rachel A; Jones, Patricia L

    2014-09-01

    Many sexual displays contain multiple components that are received through a variety of sensory modalities. Primary and secondary signal components can interact to induce novel receiver responses and become targets of sexual selection as complex signals. However, predators can also use these complex signals for prey assessment, which may limit the evolution of elaborate sexual signals. We tested whether a multimodal sexual display of the male túngara frog (Physalaemus pustulosus) increases predation risk from the fringe-lipped bat (Trachops cirrhosus) when compared with a unimodal display. We gave bats a choice to attack one of two frog models: a model with a vocal sac moving in synchrony with a mating call (multisensory cue), or a control model with the call but no vocal sac movement (unimodal cue). Bats preferred to attack the model associated with the multimodal display. Furthermore, we determined that bats perceive the vocal sac using echolocation rather than visual cues. Our data illustrate the costs associated with multimodal signaling and that sexual and natural selection pressures on the same trait are not always mediated through the same sensory modalities. These data are important when considering the role of environmental fluctuations on signal evolution as different sensory modalities will be differentially affected. PMID:25165134

  16. Computational Fluid Dynamics (CFD) Analyses in Support of Space Shuttle Main Engine (SSME) Heat Exchanger (HX) Vane Cracking Investigation

    NASA Technical Reports Server (NTRS)

    Garcia, Roberto; Benjamin, Theodore G.; Cornelison, J.; Fredmonski, A. J.

    1993-01-01

    Integration issues involved with installing the alternate turbopump (ATP) High Pressure Oxygen Turbopump (HPOTP) into the SSME have raised questions regarding the flow in the HPOTP turnaround duct (TAD). Steady-state Navier-Stokes CFD analyses have been performed by NASA and Pratt & Whitney (P&W) to address these questions. The analyses have consisted of two-dimensional axisymmetric calculations done at Marshall Space Flight Center and three-dimensional calculations performed at P&W. These analyses have identified flowfield differences between the baseline ATP and the Rocketdyne configurations. The results show that the baseline ATP configuration represents a more severe environment to the inner HX guide vane. This vane has limited life when tested in conjunction with the ATP but infinite life when tested with the current SSME HPOTP. The CFD results have helped interpret test results and have been used to assess proposed redesigns. This paper includes details of the axisymmetric model, its results, and its contribution towards resolving the problem.

  17. Computational Fluid Dynamics (CFD) analyses in support of Space Shuttle Main Engine (SSME) heat exchanger (HX) vane cracking investigation

    NASA Astrophysics Data System (ADS)

    Garcia, Roberto; Benjamin, Theodore G.; Cornelison, J.; Fredmonski, A. J.

    1993-07-01

    Integration issues involved with installing the alternate turbopump (ATP) High Pressure Oxygen Turbopump (HPOTP) into the SSME have raised questions regarding the flow in the HPOTP turnaround duct (TAD). Steady-state Navier-Stokes CFD analyses have been performed by NASA and Pratt & Whitney (P&W) to address these questions. The analyses have consisted of two-dimensional axisymmetric calculations done at Marshall Space Flight Center and three-dimensional calculations performed at P&W. These analyses have identified flowfield differences between the baseline ATP and the Rocketdyne configurations. The results show that the baseline ATP configuration represents a more severe environment to the inner HX guide vane. This vane has limited life when tested in conjunction with the ATP but infinite life when tested with the current SSME HPOTP. The CFD results have helped interpret test results and have been used to assess proposed redesigns. This paper includes details of the axisymmetric model, its results, and its contribution towards resolving the problem.

  18. QSSPN: dynamic simulation of molecular interaction networks describing gene regulation, signalling and whole-cell metabolism in human cells

    PubMed Central

    Fisher, Ciarán P.; Plant, Nicholas J.; Moore, J. Bernadette; Kierzek, Andrzej M.

    2013-01-01

    Motivation: Dynamic simulation of genome-scale molecular interaction networks will enable the mechanistic prediction of genotype–phenotype relationships. Despite advances in quantitative biology, full parameterization of whole-cell models is not yet possible. Simulation methods capable of using available qualitative data are required to develop dynamic whole-cell models through an iterative process of modelling and experimental validation. Results: We formulate quasi-steady state Petri nets (QSSPN), a novel method integrating Petri nets and constraint-based analysis to predict the feasibility of qualitative dynamic behaviours in qualitative models of gene regulation, signalling and whole-cell metabolism. We present the first dynamic simulations including regulatory mechanisms and a genome-scale metabolic network in human cell, using bile acid homeostasis in human hepatocytes as a case study. QSSPN simulations reproduce experimentally determined qualitative dynamic behaviours and permit mechanistic analysis of genotype–phenotype relationships. Availability and implementation: The model and simulation software implemented in C++ are available in supplementary material and at http://sysbio3.fhms.surrey.ac.uk/qsspn/. Contact: a.kierzek@surrey.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24064420

  19. Classifying acoustic signals into phoneme categories: average and dyslexic readers make use of complex dynamical patterns and multifractal scaling properties of the speech signal

    PubMed Central

    2015-01-01

    Several competing aetiologies of developmental dyslexia suggest that the problems with acquiring literacy skills are causally entailed by low-level auditory and/or speech perception processes. The purpose of this study is to evaluate the diverging claims about the specific deficient peceptual processes under conditions of strong inference. Theoretically relevant acoustic features were extracted from a set of artificial speech stimuli that lie on a /bAk/-/dAk/ continuum. The features were tested on their ability to enable a simple classifier (Quadratic Discriminant Analysis) to reproduce the observed classification performance of average and dyslexic readers in a speech perception experiment. The ‘classical’ features examined were based on component process accounts of developmental dyslexia such as the supposed deficit in Envelope Rise Time detection and the deficit in the detection of rapid changes in the distribution of energy in the frequency spectrum (formant transitions). Studies examining these temporal processing deficit hypotheses do not employ measures that quantify the temporal dynamics of stimuli. It is shown that measures based on quantification of the dynamics of complex, interaction-dominant systems (Recurrence Quantification Analysis and the multifractal spectrum) enable QDA to classify the stimuli almost identically as observed in dyslexic and average reading participants. It seems unlikely that participants used any of the features that are traditionally associated with accounts of (impaired) speech perception. The nature of the variables quantifying the temporal dynamics of the speech stimuli imply that the classification of speech stimuli cannot be regarded as a linear aggregate of component processes that each parse the acoustic signal independent of one another, as is assumed by the ‘classical’ aetiologies of developmental dyslexia. It is suggested that the results imply that the differences in speech perception performance between

  20. Classifying acoustic signals into phoneme categories: average and dyslexic readers make use of complex dynamical patterns and multifractal scaling properties of the speech signal.

    PubMed

    Hasselman, Fred

    2015-01-01

    Several competing aetiologies of developmental dyslexia suggest that the problems with acquiring literacy skills are causally entailed by low-level auditory and/or speech perception processes. The purpose of this study is to evaluate the diverging claims about the specific deficient peceptual processes under conditions of strong inference. Theoretically relevant acoustic features were extracted from a set of artificial speech stimuli that lie on a /bAk/-/dAk/ continuum. The features were tested on their ability to enable a simple classifier (Quadratic Discriminant Analysis) to reproduce the observed classification performance of average and dyslexic readers in a speech perception experiment. The 'classical' features examined were based on component process accounts of developmental dyslexia such as the supposed deficit in Envelope Rise Time detection and the deficit in the detection of rapid changes in the distribution of energy in the frequency spectrum (formant transitions). Studies examining these temporal processing deficit hypotheses do not employ measures that quantify the temporal dynamics of stimuli. It is shown that measures based on quantification of the dynamics of complex, interaction-dominant systems (Recurrence Quantification Analysis and the multifractal spectrum) enable QDA to classify the stimuli almost identically as observed in dyslexic and average reading participants. It seems unlikely that participants used any of the features that are traditionally associated with accounts of (impaired) speech perception. The nature of the variables quantifying the temporal dynamics of the speech stimuli imply that the classification of speech stimuli cannot be regarded as a linear aggregate of component processes that each parse the acoustic signal independent of one another, as is assumed by the 'classical' aetiologies of developmental dyslexia. It is suggested that the results imply that the differences in speech perception performance between average and

  1. Diagnostic study of coupled solar wind-magnetosphere-ionosphere dynamics in D-region ionosphere via VLF signal propagation characteristic

    NASA Astrophysics Data System (ADS)

    Nwankwo, Victor U. J.; Chakrabarti, Sandip Kumar

    2016-07-01

    Geomagnetic disturbances and storms are known to produce significant global disturbances in the ionosphere, including the middle atmosphere and troposphere. There is little understanding about the mechanism and dynamics that drive these processes in lower ionosphere. The ionosphere is also thought to be sensitive to seismic events, and it is believed that it exhibits precursory characteristics as reported in studies via characteristic anomalies in VLF signal. However, distinguishing or separating seismically induced ionospheric fluctuations from those of other origins (e.g., Solar activity, planetary and tidal waves, stratospheric warming etc.) remain vital to robust conclusion, and challenging too. The unique propagation characteristic of VLF radio signal makes it an ideal tool for the study and diagnosis of variability of D-region ionosphere. In this work, we present the analysis of solar wind-magnetosphere-ionosphere coupling dynamics in D-region ionosphere using VLF signal characteristics, and performed an investigation of previously reported 'ionospheric precursors' to understand the true origins of measured anomalies.

  2. Molecular docking and dynamics simulation analyses unraveling the differential enzymatic catalysis by plant and fungal laccases with respect to lignin biosynthesis and degradation.

    PubMed

    Awasthi, Manika; Jaiswal, Nivedita; Singh, Swati; Pandey, Veda P; Dwivedi, Upendra N

    2015-09-01

    Laccase, widely distributed in bacteria, fungi, and plants, catalyzes the oxidation of wide range of compounds. With regards to one of the important physiological functions, plant laccases are considered to catalyze lignin biosynthesis while fungal laccases are considered for lignin degradation. The present study was undertaken to explain this dual function of laccases using in-silico molecular docking and dynamics simulation approaches. Modeling and superimposition analyses of one each representative of plant and fungal laccases, namely, Populus trichocarpa and Trametes versicolor, respectively, revealed low level of similarity in the folding of two laccases at 3D levels. Docking analyses revealed significantly higher binding efficiency for lignin model compounds, in proportion to their size, for fungal laccase as compared to that of plant laccase. Residues interacting with the model compounds at the respective enzyme active sites were found to be in conformity with their role in lignin biosynthesis and degradation. Molecular dynamics simulation analyses for the stability of docked complexes of plant and fungal laccases with lignin model compounds revealed that tetrameric lignin model compound remains attached to the active site of fungal laccase throughout the simulation period, while it protrudes outwards from the active site of plant laccase. Stability of these complexes was further analyzed on the basis of binding energy which revealed significantly higher stability of fungal laccase with tetrameric compound than that of plant. The overall data suggested a situation favorable for the degradation of lignin polymer by fungal laccase while its synthesis by plant laccase. PMID:25301391

  3. Listen, follow me: Dynamic vocal signals of dominance predict emergent social rank in humans.

    PubMed

    Cheng, Joey T; Tracy, Jessica L; Ho, Simon; Henrich, Joseph

    2016-05-01

    Similar to the nonverbal signals shown by many nonhuman animals during aggressive conflicts, humans display a broad range of behavioral signals to advertise and augment their apparent size, strength, and fighting prowess when competing for social dominance. Favored by natural selection, these signals communicate the displayer's capacity and willingness to inflict harm, and increase responders' likelihood of detecting and establishing a rank asymmetry, and thus avoiding costly physical conflicts. Included among this suite of adaptations are vocal changes, which occur in a wide range of nonhuman animals (e.g., chimpanzees, rhesus monkeys) prior to aggression, but have not been systematically examined in humans. The present research tests whether and how humans use vocal pitch modulations to communicate information about their intention to dominate or submit. Results from Study 1 demonstrate that in the context of face-to-face group interactions, individuals spontaneously alter their vocal pitch in a manner consistent with rank signaling. Raising one's pitch early in the course of an interaction predicted lower emergent rank, whereas deepening one's pitch predicted higher emergent rank. Results from Study 2 provide causal evidence that these vocal shifts influence perceptions of rank and formidability. Together, findings suggest that humans use transient vocal changes to track, signal, and coordinate status relationships. PMID:27019023

  4. Activation Dynamics and Signaling Properties of Notch3 Receptor in the Developing Pulmonary Artery*

    PubMed Central

    Ghosh, Shamik; Paez-Cortez, Jesus R.; Boppidi, Karthik; Vasconcelos, Michelle; Roy, Monideepa; Cardoso, Wellington; Ai, Xingbin; Fine, Alan

    2011-01-01

    Notch3 signaling is fundamental for arterial specification of systemic vascular smooth muscle cells (VSMCs). However, the developmental role and signaling properties of the Notch3 receptor in the mouse pulmonary artery remain unknown. Here, we demonstrate that Notch3 is expressed selectively in pulmonary artery VSMCs, is activated from late fetal to early postnatal life, and is required to maintain the morphological characteristics and smooth muscle gene expression profile of the pulmonary artery after birth. Using a conditional knock-out mouse model, we show that Notch3 receptor activation in VSMCs is Jagged1-dependent. In vitro VSMC lentivirus-mediated Jagged1 knockdown, confocal localization analysis, and co-culture experiments revealed that Notch3 activation is cell-autonomous and occurs through the physical engagement of Notch3 and VSMC-derived Jagged1 in the interior of the same cell. Although the current models of mammalian Notch signaling involve a two-cell system composed of a signal-receiving cell that expresses a Notch receptor on its surface and a neighboring signal-sending cell that provides membrane-bound activating ligand, our data suggest that pulmonary artery VSMC Notch3 activation is cell-autonomous. This unique mechanism of Notch activation may play an important role in the maturation of the pulmonary artery during the transition to air breathing. PMID:21536678

  5. Dynamics of Transforming Growth Factor Beta Signaling in Wound Healing and Scarring

    PubMed Central

    Finnson, Kenneth W.; McLean, Sarah; Di Guglielmo, Gianni M.; Philip, Anie

    2013-01-01

    Significance Wound healing is an intricate biological process in which the skin, or any other tissue, repairs itself after injury. Normal wound healing relies on the appropriate levels of cytokines and growth factors to ensure that cellular responses are mediated in a coordinated manner. Among the many growth factors studied in the context of wound healing, transforming growth factor beta (TGF-β) is thought to have the broadest spectrum of effects. Recent Advances Many of the molecular mechanisms underlying the TGF-β/Smad signaling pathway have been elucidated, and the role of TGF-β in wound healing has been well characterized. Targeting the TGF-β signaling pathway using therapeutic agents to improve wound healing and/or reduce scarring has been successful in pre-clinical studies. Critical Issues Although TGF-β isoforms (β1, β2, β3) signal through the same cell surface receptors, they display distinct functions during wound healing in vivo through mechanisms that have not been fully elucidated. The challenge of translating preclinical studies targeting the TGF-β signaling pathway to a clinical setting may require more extensive preclinical research using animal models that more closely mimic wound healing and scarring in humans, and taking into account the spatial, temporal, and cell-type–specific aspects of TGF-β isoform expression and function. Future Directions Understanding the differences in TGF-β isoform signaling at the molecular level and identification of novel components of the TGF-β signaling pathway that critically regulate wound healing may lead to the discovery of potential therapeutic targets for treatment of impaired wound healing and pathological scarring. PMID:24527343

  6. Engineering light-inducible nuclear localization signals for precise spatiotemporal control of protein dynamics in living cells

    PubMed Central

    Niopek, Dominik; Benzinger, Dirk; Roensch, Julia; Draebing, Thomas; Wehler, Pierre; Eils, Roland; Di Ventura, Barbara

    2014-01-01

    The function of many eukaryotic proteins is regulated by highly dynamic changes in their nucleocytoplasmic distribution. The ability to precisely and reversibly control nuclear translocation would, therefore, allow dissecting and engineering cellular networks. Here we develop a genetically encoded, light-inducible nuclear localization signal (LINuS) based on the LOV2 domain of Avena sativa phototropin 1. LINuS is a small, versatile tag, customizable for different proteins and cell types. LINuS-mediated nuclear import is fast and reversible, and can be tuned at different levels, for instance, by introducing mutations that alter AsLOV2 domain photo-caging properties or by selecting nuclear localization signals (NLSs) of various strengths. We demonstrate the utility of LINuS in mammalian cells by controlling gene expression and entry into mitosis with blue light. PMID:25019686

  7. Non-monotonic dynamics and crosstalk in signaling pathways and their implications for pharmacology

    NASA Astrophysics Data System (ADS)

    van Wijk, Roeland; Tans, Sander J.; Wolde, Pieter Rein Ten; Mashaghi, Alireza

    2015-06-01

    Currently, drug discovery approaches commonly assume a monotonic dose-response relationship. However, the assumption of monotonicity is increasingly being challenged. Here we show that for two simple interacting linear signaling pathways that carry two different signals with different physiological responses, a non-monotonic input-output relation can arise with simple network topologies including coherent and incoherent feed-forward loops. We show that non-monotonicity of the response functions has severe implications for pharmacological treatment. Fundamental constraints are imposed on the effectiveness and toxicity of any drug independent of its chemical nature and selectivity due to the specific network structure.

  8. Analysing perturbations and nonstationarity in data series using techniques motiviated by the theory of chaotic nonlinear dynamical systems

    SciTech Connect

    Downing, D.J.; Fedorov, V.; Lawkins, W.F.; Morris, M.D.; Ostrouchov, G.

    1996-05-01

    Large data series with more than several million multivariate observations, representing tens of megabytes or even gigabytes of data, are difficult or impossible to analyze with traditional software. The shear amount of data quickly overwhelms both the available computing resources and the ability of the investigator to confidently identify meaningful patterns and trends which may be present. The purpose of this research is to give meaningful definition to `large data set analysis` and to describe and illustrate a technique for identifying unusual events in large data series. The technique presented here is based on the theory of nonlinear dynamical systems.

  9. Dynamics of the Bingham Canyon mine landslides from long-period and short-period seismic signal analysis

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

    On April 10, 2013, one of the largest landslides observed in North America occurred at the Bingham Canyon copper mine near Salt Lake City, Utah. Seismic waves recorded by the Global Seismographic Network suggest that two major slope failures occurred: at 03:31UT and at 05:06UT with long-period surface-wave magnitudes of Msw~5.1 and Msw~4.9 respectively. The combined debris of these landslides has been estimated at 150 million tonnes. We used long-period surface wave data to invert for the Landslide Force History (LFH) of each of the two events, allowing us to infer the trajectories of landslide motion and their average dynamic properties [1]. These inferred runout paths are broadly consistent with those deduced from analysis of the landslide scar using air photographs, satellite imagery and differential topographic maps. However, the total mass obtained from the LFH analysis is less consistent: using the observed runout distances for calibration [1], our inversions suggest a total landslide mass 50% less than that reported by the mining company. A further complexity, possibly related, is revealed by analysis of the short-period seismic waves, which indicates that the 05:06UT detection is in fact the composite signal of two distinct landslide seismic sources. Usually, high-frequency (HF, >1Hz) seismic signals generated by landslides are hard to observe because of their strong scattering and attenuation with distance. However, a very dense network of broadband seismic stations exists in the vicinity of the Bingham Canyon mine. Thus, we were able to compare the LFH, long-period and HF seismic signals for both events. Joint analysis of the inverted trajectory and the HF seismic signal recorded at the closest stations shows that, for the first 03:31UT event, a backward movement of the mass center started just after a final burst in the very high-frequency (VHF, >20Hz) signal. After this final burst, a tremor-like signal is observed in the VHF. This tremor-like signal

  10. Three-Dimensional Dynamic Analyses of Track-Embankment-Ground System Subjected to High Speed Train Loads

    PubMed Central

    2014-01-01

    A three-dimensional finite element model was developed to investigate dynamic response of track-embankment-ground system subjected to moving loads caused by high speed trains. The track-embankment-ground systems such as the sleepers, the ballast, the embankment, and the ground are represented by 8-noded solid elements. The infinite elements are used to represent the infinite boundary condition to absorb vibration waves induced by the passing of train load at the boundary. The loads were applied on the rails directly to simulate the real moving loads of trains. The effects of train speed on dynamic response of the system are considered. The effect of material parameters, especially the modulus changes of ballast and embankment, is taken into account to demonstrate the effectiveness of strengthening the ballast, embankment, and ground for mitigating system vibration in detail. The numerical results show that the model is reliable for predicting the amplitude of vibrations produced in the track-embankment-ground system by high-speed trains. Stiffening of fill under the embankment can reduce the vibration level, on the other hand, it can be realized by installing a concrete slab under the embankment. The influence of axle load on the vibration of the system is obviously lower than that of train speed. PMID:24723838

  11. The analysis of the influence of fractal structure of stimuli on fractal dynamics in fixational eye movements and EEG signal

    PubMed Central

    Namazi, Hamidreza; Kulish, Vladimir V.; Akrami, Amin

    2016-01-01

    One of the major challenges in vision research is to analyze the effect of visual stimuli on human vision. However, no relationship has been yet discovered between the structure of the visual stimulus, and the structure of fixational eye movements. This study reveals the plasticity of human fixational eye movements in relation to the ‘complex’ visual stimulus. We demonstrated that the fractal temporal structure of visual dynamics shifts towards the fractal dynamics of the visual stimulus (image). The results showed that images with higher complexity (higher fractality) cause fixational eye movements with lower fractality. Considering the brain, as the main part of nervous system that is engaged in eye movements, we analyzed the governed Electroencephalogram (EEG) signal during fixation. We have found out that there is a coupling between fractality of image, EEG and fixational eye movements. The capability observed in this research can be further investigated and applied for treatment of different vision disorders. PMID:27217194

  12. The analysis of the influence of fractal structure of stimuli on fractal dynamics in fixational eye movements and EEG signal.

    PubMed

    Namazi, Hamidreza; Kulish, Vladimir V; Akrami, Amin

    2016-01-01

    One of the major challenges in vision research is to analyze the effect of visual stimuli on human vision. However, no relationship has been yet discovered between the structure of the visual stimulus, and the structure of fixational eye movements. This study reveals the plasticity of human fixational eye movements in relation to the 'complex' visual stimulus. We demonstrated that the fractal temporal structure of visual dynamics shifts towards the fractal dynamics of the visual stimulus (image). The results showed that images with higher complexity (higher fractality) cause fixational eye movements with lower fractality. Considering the brain, as the main part of nervous system that is engaged in eye movements, we analyzed the governed Electroencephalogram (EEG) signal during fixation. We have found out that there is a coupling between fractality of image, EEG and fixational eye movements. The capability observed in this research can be further investigated and applied for treatment of different vision disorders. PMID:27217194

  13. The analysis of the influence of fractal structure of stimuli on fractal dynamics in fixational eye movements and EEG signal

    NASA Astrophysics Data System (ADS)

    Namazi, Hamidreza; Kulish, Vladimir V.; Akrami, Amin

    2016-05-01

    One of the major challenges in vision research is to analyze the effect of visual stimuli on human vision. However, no relationship has been yet discovered between the structure of the visual stimulus, and the structure of fixational eye movements. This study reveals the plasticity of human fixational eye movements in relation to the ‘complex’ visual stimulus. We demonstrated that the fractal temporal structure of visual dynamics shifts towards the fractal dynamics of the visual stimulus (image). The results showed that images with higher complexity (higher fractality) cause fixational eye movements with lower fractality. Considering the brain, as the main part of nervous system that is engaged in eye movements, we analyzed the governed Electroencephalogram (EEG) signal during fixation. We have found out that there is a coupling between fractality of image, EEG and fixational eye movements. The capability observed in this research can be further investigated and applied for treatment of different vision disorders.

  14. BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors

    PubMed Central

    Tadokoro, Tomomi; Gao, Xia; Hong, Charles C.; Hotten, Danielle; Hogan, Brigid L. M.

    2016-01-01

    The pseudostratified epithelium of the lung contains ciliated and secretory luminal cells and basal stem/progenitor cells. To identify signals controlling basal cell behavior we screened factors that alter their self-renewal and differentiation in a clonal organoid (tracheosphere) assay. This revealed that inhibitors of the canonical BMP signaling pathway promote proliferation but do not affect lineage choice, whereas exogenous Bmp4 inhibits proliferation and differentiation. We therefore followed changes in BMP pathway components in vivo in the mouse trachea during epithelial regeneration from basal cells after injury. The findings suggest that BMP signaling normally constrains proliferation at steady state and this brake is released transiently during repair by the upregulation of endogenous BMP antagonists. Early in repair, the packing of epithelial cells along the basal lamina increases, but density is later restored by active extrusion of apoptotic cells. Systemic administration of the BMP antagonist LDN-193189 during repair initially increases epithelial cell number but, following the shedding phase, normal density is restored. Taken together, these results reveal crucial roles for both BMP signaling and cell shedding in homeostasis of the respiratory epithelium. PMID:26811382

  15. Rapid Acquisition of Bias in Signal Detection: Dynamics of Effective Reinforcement Allocation

    ERIC Educational Resources Information Center

    Hutsell, Blake; Jacobs, Eric A.

    2012-01-01

    We investigated changes in bias (preference for one response alternative) in signal detection when relative reinforcer frequency for correct responses varied across sessions. In Experiment 1, 4 rats responded in a two-stimulus, two-response identification procedure employing temporal stimuli (short vs. long houselight presentations). Relative…

  16. Pair dynamics and the intermolecular nuclear Overhauser effect (NOE) in liquids analysed by simulation and model theories: Application to an ionic liquid

    SciTech Connect

    Gabl, Sonja; Schröder, Christian; Braun, Daniel; Steinhauser, Othmar; Weingärtner, Hermann

    2014-05-14

    Combining simulation and model theories, this paper analyses the impact of pair dynamics on the intermolecular nuclear Overhauser effect (NOE) in liquids. For the first time, we give a distance resolved NOE. When applied to the ionic liquid 1-ethyl-3-methyl-imidazolium tetrafluoroborate the NOE turns out to be of long-range nature. This behaviour translates to the experimentally measured cross- and longitudinal relaxation rates. We were able to calculate the heteronuclear NOE from simulation data, despite the high computational effort. Model theories are computationally less demanding and cover the complete frequency range of the respective spectral density function, they are usually based on a very simple pair distribution function and the solution of the diffusion equation. In order to model the simulated data sufficiently, these simplifications in structure and dynamics have to be generalised considerably.

  17. Single-cell variation leads to population invariance in NF-κB signaling dynamics

    PubMed Central

    Hughey, Jacob J.; Gutschow, Miriam V.; Bajar, Bryce T.; Covert, Markus W.

    2015-01-01

    The activation dynamics of nuclear factor (NF)-κB have been shown to affect downstream gene expression. On activation, NF-κB shuttles back and forth across the nuclear envelope. Many dynamic features of this shuttling have been characterized, and most features vary significantly with respect to ligand type and concentration. Here, we report an invariant feature with regard to NF-κB dynamics in cellular populations: the distribution—the average, as well as the variance—of the time between two nuclear entries (the period). We find that this period is conserved, regardless of concentration and across several different ligands. Intriguingly, the distributions observed at the population level are not observed in individual cells over 20-h time courses. Instead, the average period of NF-κB nuclear translocation varies considerably among single cells, and the variance is much smaller within a cell than that of the population. Finally, analysis of daughter-cell pairs and isogenic populations indicates that the dynamics of the NF-κB response is heritable but diverges over multiple divisions, on the time scale of weeks to months. These observations are contrary to the existing theory of NF-κB dynamics and suggest an additional level of control that regulates the overall distribution of translocation timing at the population level. PMID:25473117

  18. Nonlinear signal analysis to understand the dynamics of the protein sequences

    NASA Astrophysics Data System (ADS)

    Angadi, S.; Kulkarni, A.

    2008-10-01

    Recurrence plots are a useful tool to identify structure in a data set in a time resolved way qualitatively. Recurrence plots and its quantification has become an important research tool in the analysis of nonlinear dynamical systems. In the present work, we utilize the recurrence property to study the protein sequences. The sequences that we analyze belong to two distinct classes, viz., soluble proteins and proteins that form inclusion bodies when over expressed in Escherichia coli. We use Kyte-Doolittle hydrophobicity scale in the analysis. We study the underlying dynamics and extract the information which codes the essential class of a protein using simple statistical and global characteristics based features as well as some advanced features based on recurrence quantification. The extracted features are used in probability estimation using Gaussian Process Classification technique. The results give meaningful insights to the level of understanding the protein sequence dynamics.

  19. Dynamic activation of bone morphogenetic protein signaling in collagen-induced arthritis supports their role in joint homeostasis and disease

    PubMed Central

    Daans, Melina; Lories, Rik JU; Luyten, Frank P

    2008-01-01

    Introduction Rheumatoid arthritis is a chronic systemic autoimmune disease affecting peripheral joints and leading to loss of joint function. The severity and outcome of disease are dependent on the balance between inflammatory/destructive and homeostatic or repair pathways. Increasing evidence suggests a role for bone morphogenetic protein (BMP) signaling in joint homeostasis and disease. Methods Activation of BMP signaling in collagen-induced arthritis as a model of rheumatoid arthritis was studied by immunohistochemistry and Western blot for phosphorylated SMAD1/5 at different time points. Expression of different BMP ligands and noggin, a BMP antagonist, was determined on synovium and cartilage extracts of arthritic knees, at different time points, with quantitative polymerase chain reaction. At the protein level, BMP2 and BMP7 were studied with immunohistochemistry. Finally, the effect of anti-tumor necrosis factor-alpha (TNFα) treatment on the expression of BMP2, BMP7, and growth and differentiation factor-5 (GDF5) in synovium and cartilage of arthritic knees was investigated. Results A time-dependent activation of the BMP signaling pathway in collagen-induced arthritis was demonstrated with a dynamic and characteristic expression pattern of different BMP subfamily members in synovium and cartilage of arthritic knees. As severity increases, the activation of BMP signaling becomes more prominent in the invasive pannus tissue. BMP2 is present in cartilage and the hyperplastic lining layer. BMP7 is found in the sublining zone and inflammatory infiltrate. Treatment with etanercept slowed down progression of disease, but no change in expression of GDF5, BMP2, and BMP7 in synovium was found; in the cartilage, however, blocking of TNFα increased the expression of BMP7. Conclusions BMP signaling is dynamically activated in collagen-induced arthritis and is partly TNFα-independent. TNFα blocking increased the expression of BMP7 in the articular cartilage, possibly

  20. Differential Dopamine Release Dynamics in the Nucleus Accumbens Core and Shell Reveal Complementary Signals for Error Prediction and Incentive Motivation

    PubMed Central

    Cacciapaglia, Fabio; Wightman, R. Mark; Carelli, Regina M.

    2015-01-01

    Mesolimbic dopamine (DA) is phasically released during appetitive behaviors, though there is substantive disagreement about the specific purpose of these DA signals. For example, prediction error (PE) models suggest a role of learning, while incentive salience (IS) models argue that the DA signal imbues stimuli with value and thereby stimulates motivated behavior. However, within the nucleus accumbens (NAc) patterns of DA release can strikingly differ between subregions, and as such, it is possible that these patterns differentially contribute to aspects of PE and IS. To assess this, we measured DA release in subregions of the NAc during a behavioral task that spatiotemporally separated sequential goal-directed stimuli. Electrochemical methods were used to measure subsecond NAc dopamine release in the core and shell during a well learned instrumental chain schedule in which rats were trained to press one lever (seeking; SL) to gain access to a second lever (taking; TL) linked with food delivery, and again during extinction. In the core, phasic DA release was greatest following initial SL presentation, but minimal for the subsequent TL and reward events. In contrast, phasic shell DA showed robust release at all task events. Signaling decreased between the beginning and end of sessions in the shell, but not core. During extinction, peak DA release in the core showed a graded decrease for the SL and pauses in release during omitted expected rewards, whereas shell DA release decreased predominantly during the TL. These release dynamics suggest parallel DA signals capable of supporting distinct theories of appetitive behavior. SIGNIFICANCE STATEMENT Dopamine signaling in the brain is important for a variety of cognitive functions, such as learning and motivation. Typically, it is assumed that a single dopamine signal is sufficient to support these cognitive functions, though competing theories disagree on how dopamine contributes to reward-based behaviors. Here, we have

  1. Analysing the spatio-temporal organization of sediment dynamics at the hillslope scale using a process based erosion model

    NASA Astrophysics Data System (ADS)

    Scherer, U.; Zehe, E.; Ehret, U.; Kleidon, A.

    2012-04-01

    The morphology of soil covered hillslopes tends to a characteristic convex-concave shape. In hilly landscapes, where erosion rates do not exceed the weathering rates of bedrock material, the form of hillslopes is convex near the hilltop and becomes increasingly planar further downslope with the steepest descent in the middle of the slope. This typical shape is the result of long term erosion and sediment redistribution processes driven by a topographic gradient and climatic forcing. Erosion rates depend on slope, soil properties, vegetation cover and rainfall/runoff rates. The morphology of hillslopes is thus the result of a trade-off between all these parameters controlling the relation of detachment, transport and deposition rates of sediments as well as feedback mechanisms on the driving gradient. Sediment flux increases with increasing slope but higher sediment transport rates deplete the driving gradient and thus reduce sediment export. We hypothesize that sediment export is maximized under the condition of maintaining the driving gradient and that this trade-off implies a typical shape and steepness of slopes. We used the process based model CATFLOW-SED to verify this hypothesis and to better understand the spatio-temporal organisation of sediment dynamics at the hillslope scale. CATFLOW-SED is a continuous, dynamic, spatially distributed model. Soil water dynamics is described by the Richards equation, including an effective approach for preferential flow that is numerically solved by an implicit mass conservative Picard iteration. Evaporation and transpiration is simulated, using an advanced approach based on the Penman-Monteith equation. The model simulates overland flow as sheet flow using the diffusion wave equation. Soil detachment is related to the attacking forces of rainfall and overland flow. The detachment rate further depends on the model parameter erosion resistance, which is characterized by soil properties, land use and management practice

  2. An automated programmable platform enabling multiplex dynamic stimuli delivery and cellular response monitoring for high-throughput suspension single-cell signaling studies.

    PubMed

    He, Luye; Kniss, Ariel; San-Miguel, Adriana; Rouse, Tel; Kemp, Melissa L; Lu, Hang

    2015-03-21

    Cell signaling events are orchestrated by dynamic external biochemical cues. By rapidly perturbing cells with dynamic inputs and examining the output from these systems, one could study the structure and dynamic properties of a cellular signaling network. Conventional experimental techniques limit the implementation of these systematic approaches due to the lack of sophistication in manipulating individual cells and the fluid microenvironment around them; existing microfluidic technologies thus far are mainly targeting adherent cells. In this paper we present an automated platform to interrogate suspension cells with dynamic stimuli while simultaneously monitoring cellular responses in a high-throughput manner at single-cell resolution. We demonstrate the use of this platform in an experiment to measure Jurkat T cells in response to distinct dynamic patterns of stimuli; we find cells exhibit highly heterogeneous responses under each stimulation condition. More interestingly, these cells act as low-pass filters, only entrained to the low frequency stimulus signals. We also demonstrate that this platform can be easily programmed to actively generate arbitrary dynamic signals. We envision our platform to be useful in other contexts to study cellular signaling dynamics, which may be difficult using conventional experimental methods. PMID:25609410

  3. Fast Dynamic Simulation-Based Small Signal Stability Assessment and Control

    SciTech Connect

    Acharya, Naresh; Baone, Chaitanya; Veda, Santosh; Dai, Jing; Chaudhuri, Nilanjan; Leonardi, Bruno; Sanches-Gasca, Juan; Diao, Ruisheng; Wu, Di; Huang, Zhenyu; Zhang, Yu; Jin, Shuangshuang; Zheng, Bin; Chen, Yousu

    2014-12-31

    Power grid planning and operation decisions are made based on simulation of the dynamic behavior of the system. Enabling substantial energy savings while increasing the reliability of the aging North American power grid through improved utilization of existing transmission assets hinges on the adoption of wide-area measurement systems (WAMS) for power system stabilization. However, adoption of WAMS alone will not suffice if the power system is to reach its full entitlement in stability and reliability. It is necessary to enhance predictability with "faster than real-time" dynamic simulations that will enable the dynamic stability margins, proactive real-time control, and improve grid resiliency to fast time-scale phenomena such as cascading network failures. Present-day dynamic simulations are performed only during offline planning studies, considering only worst case conditions such as summer peak, winter peak days, etc. With widespread deployment of renewable generation, controllable loads, energy storage devices and plug-in hybrid electric vehicles expected in the near future and greater integration of cyber infrastructure (communications, computation and control), monitoring and controlling the dynamic performance of the grid in real-time would become increasingly important. The state-of-the-art dynamic simulation tools have limited computational speed and are not suitable for real-time applications, given the large set of contingency conditions to be evaluated. These tools are optimized for best performance of single-processor computers, but the simulation is still several times slower than real-time due to its computational complexity. With recent significant advances in numerical methods and computational hardware, the expectations have been rising towards more efficient and faster techniques to be implemented in power system simulators. This is a natural expectation, given that the core solution algorithms of most commercial simulators were developed

  4. SRM Internal Flow Tests and Computational Fluid Dynamic Analysis. Volume 3; Titan, ASRM, and Subscale Motor Analyses

    NASA Technical Reports Server (NTRS)

    1995-01-01

    A computational fluid dynamics (CFD) analysis has been performed on the aft slot region of the Titan 4 Solid Rocket Motor Upgrade (SRMU). This analysis was performed in conjunction with MSFC structural modeling of the propellant grain to determine if the flow field induced stresses would adversely alter the propellant geometry to the extent of causing motor failure. The results of the coupled CFD/stress analysis have shown that there is a continual increase of flow field resistance at the aft slot due to the aft segment propellant grain being progressively moved radially toward the centerline of the motor port. This 'bootstrapping' effect between grain radial movement and internal flow resistance is conducive to causing a rapid motor failure.

  5. Analyses of the Photospheric Magnetic Dynamics in Solar Active Region 11117 Using an Advanced CESE-MHD Model

    NASA Astrophysics Data System (ADS)

    Jiang, Chaowei; Wu, Shi; Feng, Xueshang

    2016-05-01

    In this study, the photospheric vector magnetograms obtained by Helioseismic and Magnetic Imager on-board the Solar Dynamics Observatory are used as boundary conditions for a CESE-MHD model to investigate some photosphere characteristics around the time of a confined flare in solar active region NOAA AR 11117. We report our attempt of characterizing a more realistic solar atmosphere by including a plasma with temperature stratified from the photosphere to the corona in the CESE-MHD model. The resulted photospheric transverse flow is comparable to the apparent movements of the magnetic flux features that demonstrates shearing and rotations. We calculated the relevant parameters such as the magnetic energy flux and helicity flux, and with analysis of these parameters, we find that magnetic non-potentiality is transported across the photosphere into the corona in the simulated time interval, which might provide a favorable condition for producing the flare.

  6. Functional analyses in the milkweed bug Oncopeltus fasciatus (Hemiptera) support a role for Wnt signaling in body segmentation but not appendage development.

    PubMed

    Angelini, David R; Kaufman, Thomas C

    2005-07-15

    Specification of the proximal-distal (PD) axis of insect appendages is best understood in Drosophila melanogaster, where conserved signaling molecules encoded by the genes decapentaplegic (dpp) and wingless (wg) play key roles. However, the development of appendages from imaginal discs as in Drosophila is a derived state, while more basal insects produce appendages from embryonic limb buds. Therefore, the universality of the Drosophila limb PD axis specification mechanism has been debated since dpp expression in more basal insect species differs dramatically from Drosophila. Here, we test the function of Wnt signaling in the development of the milkweed bug Oncopeltus fasciatus, a species with the basal state of appendage development from limb buds. RNA interference of wg and pangolin (pan) produce defects in the germband and eyes, but not in the appendages. Distal-less and dachshund, two genes regulated by Wg signaling in Drosophila and expressed in specific PD domains along the limbs of both species, are expressed normally in the limbs of pan-depleted Oncopeltus embryos. Despite these apparently paradoxical results, Armadillo protein, the transducer of Wnt signaling, does not accumulate properly in the nuclei of cells in the legs of pan-depleted embryos. In contrast, engrailed RNAi in Oncopeltus produces cuticular and appendage defects similar to Drosophila. Therefore, our data suggest that Wg signaling is functionally conserved in the development of the germband, while it is not essential in the specification of the limb PD axis in Oncopeltus and perhaps basal insects. PMID:15939417

  7. Microbial contributions to C and N dynamics in decaying litter elucidated by amino acid and amino sugar analyses

    NASA Astrophysics Data System (ADS)

    Hobara, S.; Osono, T.; Noro, K.; Hirota, M.; Benner, R. H.

    2011-12-01

    There is still much to be revealed about carbon (C) and nitrogen (N) dynamics in terrestrial soil systems. The objectives of this study were to identify molecular changes in composition during plant litter decomposition and gain insights about microbial contributions to C and N dynamics in decaying litter. Litter bag experiments with three plant species, Miscanthus sinensis, Pinus densiflora and Quercus crispula, were conducted for three years, and the concentrations of C, N, amino acids and amino sugars were determined at various times during the experiments. Mass loss (AFDW) ranged from 66-90% for the plant tissues. The weight %C remained fairly constant, whereas the weight %N increased throughout the study indicating N immobilization was occurring. The percentages of C as amino acids and amino sugars also increased throughout the study suggesting these biomolecules were largely of microbial origin. The increasing yields of amino acids and amino sugars were inversely related to overall C loss from the litter material. As microorganisms degraded the plant litter they left behind molecular signatures that were useful predictors of the extent of overall degradation. The C/N ratio of litter decreased throughout the study and was inversely related to galactosamine yields. The glucosamine/galactosamine (GlcN/GalN) ratio gradually declined to values near 2 by the end of the study. Galactoasamine is more abundant in bacteria than fungi, and the declining GlcN/GalN ratio suggest the relative contributions of bacterial to litter C and N increased relative to contributions from fungi. A cluster analysis of 0- and 36-month litters based on amino acid and amino sugar composition showed that 0-month litters of three plant species were separated from 36-month litters, suggesting common diagenetic pathways during decomposition irrespective of plant species. The microbial decomposers contribute to N immobilization and their contributions to the C and N content of litter increases

  8. Voxel-by-voxel correlations of perfusion, substrate, and metabolite signals in dynamic hyperpolarized (13) C imaging.

    PubMed

    Lau, Justin Y C; Chen, Albert P; Gu, Yi-Ping; Cunningham, Charles H

    2016-08-01

    In this study, a mixture of pyruvic acid and the perfusion agent HP001 was co-polarized for simultaneous assessment of perfusion and metabolism in vivo. The pre-polarized mixture was administered to rats with subcutaneous MDA-MB-231 breast cancer xenografts and imaged using an interleaved sequence with designed spectral-spatial pulses and flyback echo-planar readouts. Voxel-by-voxel signal correlations from 10 animals (15 data sets) were analyzed for tumour, kidney, and muscle regions of interest. The relationship between perfusion and hyperpolarized signal was explored on a voxel-by-voxel basis in various metabolically active tissues, including tumour, healthy kidneys, and skeletal muscle. Positive pairwise correlations between lactate, pyruvate, and HP001 observed in all 10 tumours suggested that substrate delivery was the dominant factor limiting the conversion of pyruvate to lactate in the tumour model used in this study. On the other hand, in cases where conversion is the limiting factor, such as in healthy kidneys, both pyruvate and lactate can act as excellent perfusion markers. In intermediate cases between the two limits, such as in skeletal muscle, some perfusion information may be inferred from the (pyruvate + lactate) signal distribution. Co-administration of pyruvate with a dynamic nuclear polarization (DNP) perfusion agent is an effective approach for distinguishing between slow metabolism and poor perfusion and a practical strategy for lactate signal normalization to account for substrate delivery, especially in cases of rapid pyruvate-to-lactate conversion and in poorly perfused regions with inadequate pyruvate signal-to-noise ratio for reliable determination of the lactate-to-pyruvate ratio. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27295304

  9. PCP Signaling between Migrating Neurons and their Planar-Polarized Neuroepithelial Environment Controls Filopodial Dynamics and Directional Migration

    PubMed Central

    Moens, Cecilia B.

    2016-01-01

    The planar cell polarity (PCP) pathway is a cell-contact mediated mechanism for transmitting polarity information between neighboring cells. PCP “core components” (Vangl, Fz, Pk, Dsh, and Celsr) are essential for a number of cell migratory events including the posterior migration of facial branchiomotor neurons (FBMNs) in the plane of the hindbrain neuroepithelium in zebrafish and mice. While the mechanism by which PCP signaling polarizes static epithelial cells is well understood, how PCP signaling controls highly dynamic processes like neuronal migration remains an important outstanding question given that PCP components have been implicated in a range of directed cell movements, particularly during vertebrate development. Here, by systematically disrupting PCP signaling in a rhombomere-restricted manner we show that PCP signaling is required both within FBMNs and the hindbrain rhombomere 4 environment at the time when they initiate their migration. Correspondingly, we demonstrate planar polarized localization of PCP core components Vangl2 and Fzd3a in the hindbrain neuroepithelium, and transient localization of Vangl2 at the tips of retracting FBMN filopodia. Using high-resolution timelapse imaging of FBMNs in genetic chimeras we uncover opposing cell-autonomous and non-cell-autonomous functions for Fzd3a and Vangl2 in regulating FBMN protrusive activity. Within FBMNs, Fzd3a is required to stabilize filopodia while Vangl2 has an antagonistic, destabilizing role. However, in the migratory environment Fzd3a acts to destabilize FBMN filopodia while Vangl2 has a stabilizing role. Together, our findings suggest a model in which PCP signaling between the planar polarized neuroepithelial environment and FBMNs directs migration by the selective stabilization of FBMN filopodia. PMID:26990447

  10. Noise-driven signal transmission device using molecular dynamics of organic polymers

    NASA Astrophysics Data System (ADS)

    Asakawa, Naoki; Kanki, Teruo; Tanaka, Hidekazu

    2014-03-01

    Stochastic threshold devices using trap-filling transition coupled with molecular dynamics in poly(3-alkyl thiophene)s [P3ATs] were fabricated as potential key devices for noise-driven bio-inspired sensors and infor- mation processors. This article deals with variable-temperature direct current conductivity and alternating current impedance measurements for vertical-type device elements of Au/regioregular poly(3-decylthiophene) [RR-P3DT] (thickness:100nm)/Au, which show multiple conducting states and quasi-stochastic transitions between these states. Noise measurements indicate the ω-2-type (if V < VTFT = 10V) and ω-1-type (if V > VTFT) power spectral densities, where V and VTFT are an applied voltage and the voltage for trap-filling transition(TFT),respectively. The noise generation is due to TFT that associated with twist dynamics of π-conjugated polymers near the order-disorder phase transition. At 298K, the quasi-stochastic behavior is more noticeable for RR-P3DT than poly(3-hexylthiophene) [RR-P3HT]. The dynamics of the order-disorder phase transition (ODT) for powder samples were also investigated by differential scanning calorimetry (DSC) measurements and high-resolution solid-state C NMR spectroscopy, and the correlation of molecular structure and dynamics with electric properties was discussed.

  11. Dynamics of Virus-Receptor Interactions in Virus Binding, Signaling, and Endocytosis

    PubMed Central

    Boulant, Steeve; Stanifer, Megan; Lozach, Pierre-Yves

    2015-01-01

    During viral infection the first challenge that viruses have to overcome is gaining access to the intracellular compartment. The infection process starts when the virus contacts the surface of the host cell. A complex series of events ensues, including diffusion at the host cell membrane surface, binding to receptors, signaling, internalization, and delivery of the genetic information. The focus of this review is on the very initial steps of virus entry, from receptor binding to particle uptake into the host cell. We will discuss how viruses find their receptor, move to sub-membranous regions permissive for entry, and how they hijack the receptor-mediated signaling pathway to promote their internalization. PMID:26043381

  12. Dynamic Frequency Analyses of Lower Extremity Muscles during Sit-To-Stand Motion for the Patients with Knee Osteoarthritis

    PubMed Central

    Suzuki, Kentaro; Yagi, Masahide

    2016-01-01

    Objective Muscle activities during the sit-to-stand motion (STS) are characterized by coordinated movements between hip extensors and knee extensors. However, previous reports regarding the STS and lower extremity muscle activities have focused on some quantitative assessment, but little qualitative research. This study aimed to examine the muscle activities of the lower extremity both quantitatively and qualitatively. Methods Study participants included 13 patients with knee osteoarthritis (knee OA) and 11 age-matched asymptomatic controls. The task was STS from a chair with a height-adjustable seat. EMG activities were acquired using surface electromyogram. The root mean square signals normalized as a percentage of maximum voluntary isometric contraction values (RMS%MVC) and the mean power frequency (MPF) were calculated. Results During STS, knee OA patients had increased RMS%MVC of the vastus medialis and raised MPF of the rectus femoris before buttocks-off. Conclusion These findings suggest that STS of knee OA patients not only increased relative muscle activity of the vastus medialis, but also enlisted the rectus femoris in knee extension to improve muscle contraction force by activating more type II fibers to accomplish buttocks-off. PMID:26807578

  13. Human brain dynamics: the analysis of EEG signals with Tsallis information measure

    NASA Astrophysics Data System (ADS)

    Capurro, A.; Diambra, L.; Lorenzo, D.; Macadar, O.; Martin, M. T.; Mostaccio, C.; Plastino, A.; Pérez, J.; Rofman, E.; Torres, M. E.; Velluti, J.

    We undertake the study of human EEG-signals by recourse to a wavelet based multiresolution analysis as adapted to an Information-Measure-Scenario. Different information measures are employed. It is shown that non-extensive ones seem to be of particular usefulness. Their use opens up perspectives of building up automatic detection devices. Conjectures concerning general characteristics of focal epilepsy are formulated on the basis of a Tsallis-type of analysis.

  14. CaM/BAG5/Hsc70 signaling complex dynamically regulates leaf senescence.

    PubMed

    Li, Luhua; Xing, Yangfei; Chang, Dong; Fang, Shasha; Cui, Boyang; Li, Qi; Wang, Xuejie; Guo, Shang; Yang, Xue; Men, Shuzhen; Shen, Yuequan

    2016-01-01

    Calcium signaling plays an essential role in plant cell physiology, and chaperone-mediated protein folding directly regulates plant programmed cell death. The Arabidopsis thaliana protein AtBAG5 (Bcl-2-associated athanogene 5) is unique in that it contains both a BAG domain capable of binding Hsc70 (Heat shock cognate protein 70) and a characteristic IQ motif that is specific for Ca(2+)-free CaM (Calmodulin) binding and hence acts as a hub linking calcium signaling and the chaperone system. Here, we determined crystal structures of AtBAG5 alone and in complex with Ca(2+)-free CaM. Structural and biochemical studies revealed that Ca(2+)-free CaM and Hsc70 bind AtBAG5 independently, whereas Ca(2+)-saturated CaM and Hsc70 bind AtBAG5 with negative cooperativity. Further in vivo studies confirmed that AtBAG5 localizes to mitochondria and that its overexpression leads to leaf senescence symptoms including decreased chlorophyll retention and massive ROS production in dark-induced plants. Mutants interfering the CaM/AtBAG5/Hsc70 complex formation leads to different phenotype of leaf senescence. Collectively, we propose that the CaM/AtBAG5/Hsc70 signaling complex plays an important role in regulating plant senescence. PMID:27539741

  15. Multistage estimation of received carrier signal parameters under very high dynamic conditions of the receiver

    NASA Technical Reports Server (NTRS)

    Kumar, Rajendra (Inventor)

    1990-01-01

    A multistage estimator is provided for the parameters of a received carrier signal possibly phase-modulated by unknown data and experiencing very high Doppler, Doppler rate, etc., as may arise, for example, in the case of Global Positioning Systems (GPS) where the signal parameters are directly related to the position, velocity and jerk of the GPS ground-based receiver. In a two-stage embodiment of the more general multistage scheme, the first stage, selected to be a modified least squares algorithm referred to as differential least squares (DLS), operates as a coarse estimator resulting in higher rms estimation errors but with a relatively small probability of the frequency estimation error exceeding one-half of the sampling frequency, provides relatively coarse estimates of the frequency and its derivatives. The second stage of the estimator, an extended Kalman filter (EKF), operates on the error signal available from the first stage refining the overall estimates of the phase along with a more refined estimate of frequency as well and in the process also reduces the number of cycle slips.

  16. Multistage estimation of received carrier signal parameters under very high dynamic conditions of the receiver

    NASA Technical Reports Server (NTRS)

    Kumar, Rajendra (Inventor)

    1991-01-01

    A multistage estimator is provided for the parameters of a received carrier signal possibly phase-modulated by unknown data and experiencing very high Doppler, Doppler rate, etc., as may arise, for example, in the case of Global Positioning Systems (GPS) where the signal parameters are directly related to the position, velocity and jerk of the GPS ground-based receiver. In a two-stage embodiment of the more general multistage scheme, the first stage, selected to be a modified least squares algorithm referred to as differential least squares (DLS), operates as a coarse estimator resulting in higher rms estimation errors but with a relatively small probability of the frequency estimation error exceeding one-half of the sampling frequency, provides relatively coarse estimates of the frequency and its derivatives. The second stage of the estimator, an extended Kalman filter (EKF), operates on the error signal available from the first stage refining the overall estimates of the phase along with a more refined estimate of frequency as well and in the process also reduces the number of cycle slips.

  17. Correlation dynamics and enhanced signals for the identification of serial biomolecules and DNA bases

    NASA Astrophysics Data System (ADS)

    Ahmed, Towfiq; Haraldsen, Jason T.; Rehr, John J.; Di Ventra, Massimiliano; Schuller, Ivan; Balatsky, Alexander V.

    2014-03-01

    Nanopore-based sequencing has demonstrated a significant potential for the development of fast, accurate, and cost-efficient fingerprinting techniques for next generation molecular detection and sequencing. We propose a specific multilayered graphene-based nanopore device architecture for the recognition of single biomolecules. Molecular detection and analysis can be accomplished through the detection of transverse currents as the molecule or DNA base translocates through the nanopore. To increase the overall signal-to-noise ratio and the accuracy, we implement a new ‘multi-point cross-correlation’ technique for identification of DNA bases or other molecules on the single molecular level. We demonstrate that the cross-correlations between each nanopore will greatly enhance the transverse current signal for each molecule. We implement first-principles transport calculations for DNA bases surveyed across a multilayered graphene nanopore system to illustrate the advantages of the proposed geometry. A time-series analysis of the cross-correlation functions illustrates the potential of this method for enhancing the signal-to-noise ratio. This work constitutes a significant step forward in facilitating fingerprinting of single biomolecules using solid state technology.