WorldWideScience

Sample records for large signaling complexes

  1. Large erupted complex odontoma

    Directory of Open Access Journals (Sweden)

    Vijeev Vasudevan

    2009-01-01

    Full Text Available Odontomas are a heterogeneous group of jaw bone lesions, classified as odontogenic tumors which usually include well-diversified dental tissues. Odontoma is a term introduced to the literature by Broca in 1867. Trauma, infection and hereditary factors are the possible causes of forming this kind of lesions. Among odontogenic tumors, they constitute about 2/3 of cases. These lesions usually develop slowly and asymptomatically, and in most cases they do not cross the bone borders. Two types of odontoma are recognized: compound and complex. Complex odontomas are less common than the compound variety in the ratio 1:2.3. Eruption of an odontoma in the oral cavity is rare. We present a case of complex odontoma, in which apparent eruption has occurred in the area of the right maxillary second molar region.

  2. Chansporter complexes in cell signaling.

    Science.gov (United States)

    Abbott, Geoffrey W

    2017-09-01

    Ion channels facilitate diffusion of ions across cell membranes for such diverse purposes as neuronal signaling, muscular contraction, and fluid homeostasis. Solute transporters often utilize ionic gradients to move aqueous solutes up their concentration gradient, also fulfilling a wide variety of tasks. Recently, an increasing number of ion channel-transporter ('chansporter') complexes have been discovered. Chansporter complex formation may overcome what could otherwise be considerable spatial barriers to rapid signal integration and feedback between channels and transporters, the ions and other substrates they transport, and environmental factors to which they must respond. Here, current knowledge in this field is summarized, covering both heterologous expression structure/function findings and potential mechanisms by which chansporter complexes fulfill contrasting roles in cell signaling in vivo. © 2017 Federation of European Biochemical Societies.

  3. Assembling large, complex environmental metagenomes

    Energy Technology Data Exchange (ETDEWEB)

    Howe, A. C. [Michigan State Univ., East Lansing, MI (United States). Microbiology and Molecular Genetics, Plant Soil and Microbial Sciences; Jansson, J. [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Earth Sciences Division; Malfatti, S. A. [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Tringe, S. G. [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Tiedje, J. M. [Michigan State Univ., East Lansing, MI (United States). Microbiology and Molecular Genetics, Plant Soil and Microbial Sciences; Brown, C. T. [Michigan State Univ., East Lansing, MI (United States). Microbiology and Molecular Genetics, Computer Science and Engineering

    2012-12-28

    The large volumes of sequencing data required to sample complex environments deeply pose new challenges to sequence analysis approaches. De novo metagenomic assembly effectively reduces the total amount of data to be analyzed but requires significant computational resources. We apply two pre-assembly filtering approaches, digital normalization and partitioning, to make large metagenome assemblies more computationaly tractable. Using a human gut mock community dataset, we demonstrate that these methods result in assemblies nearly identical to assemblies from unprocessed data. We then assemble two large soil metagenomes from matched Iowa corn and native prairie soils. The predicted functional content and phylogenetic origin of the assembled contigs indicate significant taxonomic differences despite similar function. The assembly strategies presented are generic and can be extended to any metagenome; full source code is freely available under a BSD license.

  4. Large scale analysis of signal reachability.

    Science.gov (United States)

    Todor, Andrei; Gabr, Haitham; Dobra, Alin; Kahveci, Tamer

    2014-06-15

    Major disorders, such as leukemia, have been shown to alter the transcription of genes. Understanding how gene regulation is affected by such aberrations is of utmost importance. One promising strategy toward this objective is to compute whether signals can reach to the transcription factors through the transcription regulatory network (TRN). Due to the uncertainty of the regulatory interactions, this is a #P-complete problem and thus solving it for very large TRNs remains to be a challenge. We develop a novel and scalable method to compute the probability that a signal originating at any given set of source genes can arrive at any given set of target genes (i.e., transcription factors) when the topology of the underlying signaling network is uncertain. Our method tackles this problem for large networks while providing a provably accurate result. Our method follows a divide-and-conquer strategy. We break down the given network into a sequence of non-overlapping subnetworks such that reachability can be computed autonomously and sequentially on each subnetwork. We represent each interaction using a small polynomial. The product of these polynomials express different scenarios when a signal can or cannot reach to target genes from the source genes. We introduce polynomial collapsing operators for each subnetwork. These operators reduce the size of the resulting polynomial and thus the computational complexity dramatically. We show that our method scales to entire human regulatory networks in only seconds, while the existing methods fail beyond a few tens of genes and interactions. We demonstrate that our method can successfully characterize key reachability characteristics of the entire transcriptions regulatory networks of patients affected by eight different subtypes of leukemia, as well as those from healthy control samples. All the datasets and code used in this article are available at bioinformatics.cise.ufl.edu/PReach/scalable.htm. © The Author 2014

  5. Reliability of large and complex systems

    CERN Document Server

    Kolowrocki, Krzysztof

    2014-01-01

    Reliability of Large and Complex Systems, previously titled Reliability of Large Systems, is an innovative guide to the current state and reliability of large and complex systems. In addition to revised and updated content on the complexity and safety of large and complex mechanisms, this new edition looks at the reliability of nanosystems, a key research topic in nanotechnology science. The author discusses the importance of safety investigation of critical infrastructures that have aged or have been exposed to varying operational conditions. This reference provides an asympt

  6. Large-Scale Transit Signal Priority Implementation

    OpenAIRE

    Lee, Kevin S.; Lozner, Bailey

    2018-01-01

    In 2016, the District Department of Transportation (DDOT) deployed Transit Signal Priority (TSP) at 195 intersections in highly urbanized areas of Washington, DC. In collaboration with a broader regional implementation, and in partnership with the Washington Metropolitan Area Transit Authority (WMATA), DDOT set out to apply a systems engineering–driven process to identify, design, test, and accept a large-scale TSP system. This presentation will highlight project successes and lessons learned.

  7. Large-scale Complex IT Systems

    OpenAIRE

    Sommerville, Ian; Cliff, Dave; Calinescu, Radu; Keen, Justin; Kelly, Tim; Kwiatkowska, Marta; McDermid, John; Paige, Richard

    2011-01-01

    This paper explores the issues around the construction of large-scale complex systems which are built as 'systems of systems' and suggests that there are fundamental reasons, derived from the inherent complexity in these systems, why our current software engineering methods and techniques cannot be scaled up to cope with the engineering challenges of constructing such systems. It then goes on to propose a research and education agenda for software engineering that identifies the major challen...

  8. Large-scale complex IT systems

    OpenAIRE

    Sommerville, Ian; Cliff, Dave; Calinescu, Radu; Keen, Justin; Kelly, Tim; Kwiatkowska, Marta; McDermid, John; Paige, Richard

    2012-01-01

    12 pages, 2 figures This paper explores the issues around the construction of large-scale complex systems which are built as 'systems of systems' and suggests that there are fundamental reasons, derived from the inherent complexity in these systems, why our current software engineering methods and techniques cannot be scaled up to cope with the engineering challenges of constructing such systems. It then goes on to propose a research and education agenda for software engineering that ident...

  9. A Signal-Interleaving Complex Bandpass Sigma-Delta Converter

    DEFF Research Database (Denmark)

    Wad, Paul Emmanuel

    1997-01-01

    Complex or quadrature Sigma-Delta converters operate on complex signals, i.e. signals consisting of a real and an imaginary component, whereas conventional converters operate only on real signals. The advantage of complex signal processing in the discrete-time domain is that the entire sampling...

  10. Exome localization of complex disease association signals

    Directory of Open Access Journals (Sweden)

    Lewis Cathryn M

    2011-02-01

    Full Text Available Abstract Background Genome-wide association studies (GWAS of common diseases have had a tremendous impact on genetic research over the last five years; the field is now moving from microarray-based technology towards next-generation sequencing. To evaluate the potential of association studies for complex diseases based on exome sequencing we analysed the distribution of association signal with respect to protein-coding genes based on GWAS data for seven diseases from the Wellcome Trust Case Control Consortium. Results We find significant concentration of association signal in exons and genes for Crohn's Disease, Type 1 Diabetes and Bipolar Disorder, but also observe enrichment from up to 40 kilobases upstream to 40 kilobases downstream of protein-coding genes for Crohn's Disease and Type 1 Diabetes; the exact extent of the distribution is disease dependent. Conclusions Our work suggests that exome sequencing may be a feasible approach to find genetic variation associated with complex disease. Extending the exome sequencing to include flanking regions therefore promises further improvement of covering disease-relevant variants.

  11. Large branched self-assembled DNA complexes

    International Nuclear Information System (INIS)

    Tosch, Paul; Waelti, Christoph; Middelberg, Anton P J; Davies, A Giles

    2007-01-01

    Many biological molecules have been demonstrated to self-assemble into complex structures and networks by using their very efficient and selective molecular recognition processes. The use of biological molecules as scaffolds for the construction of functional devices by self-assembling nanoscale complexes onto the scaffolds has recently attracted significant attention and many different applications in this field have emerged. In particular DNA, owing to its inherent sophisticated self-organization and molecular recognition properties, has served widely as a scaffold for various nanotechnological self-assembly applications, with metallic and semiconducting nanoparticles, proteins, macromolecular complexes, inter alia, being assembled onto designed DNA scaffolds. Such scaffolds may typically contain multiple branch-points and comprise a number of DNA molecules selfassembled into the desired configuration. Previously, several studies have used synthetic methods to produce the constituent DNA of the scaffolds, but this typically constrains the size of the complexes. For applications that require larger self-assembling DNA complexes, several tens of nanometers or more, other techniques need to be employed. In this article, we discuss a generic technique to generate large branched DNA macromolecular complexes

  12. Large complex ovarian cyst managed by laparoscopy

    OpenAIRE

    Dipak J. Limbachiya; Ankit Chaudhari; Grishma P. Agrawal

    2017-01-01

    Complex ovarian cyst with secondary infection is a rare disease that hardly responds to the usual antibiotic treatment. Most of the times, it hampers day to day activities of women. It is commonly known to cause pain and fever. To our surprise, in our case the cyst was large enough to compress the ureter and it was adherent to the surrounding structures. Laparoscopic removal of the cyst was done and specimen was sent for histopathological examination.

  13. Labor Inhibits Placental Mechanistic Target of Rapamycin Complex 1 Signaling

    Science.gov (United States)

    LAGER, Susanne; AYE, Irving L.M.H.; GACCIOLI, Francesca; RAMIREZ, Vanessa I.; JANSSON, Thomas; POWELL, Theresa L.

    2014-01-01

    Introduction Labor induces a myriad of changes in placental gene expression. These changes may represent a physiological adaptation inhibiting placental cellular processes associated with a high demand for oxygen and energy (e.g., protein synthesis and active transport) thereby promoting oxygen and glucose transfer to the fetus. We hypothesized that mechanistic target of rapamycin complex 1 (mTORC1) signaling, a positive regulator of trophoblast protein synthesis and amino acid transport, is inhibited by labor. Methods Placental tissue was collected from healthy, term pregnancies (n=15 no-labor; n=12 labor). Activation of Caspase-1, IRS1/Akt, STAT, mTOR, and inflammatory signaling pathways was determined by Western blot. NFκB p65 and PPARγ DNA binding activity was measured in isolated nuclei. Results Labor increased Caspase-1 activation and mTOR complex 2 signaling, as measured by phosphorylation of Akt (S473). However, mTORC1 signaling was inhibited in response to labor as evidenced by decreased phosphorylation of mTOR (S2448) and 4EBP1 (T37/46 and T70). Labor also decreased NFκB and PPARγ DNA binding activity, while having no effect on IRS1 or STAT signaling pathway. Discussion and conclusion Several placental signaling pathways are affected by labor, which has implications for experimental design in studies of placental signaling. Inhibition of placental mTORC1 signaling in response to labor may serve to down-regulate protein synthesis and amino acid transport, processes that account for a large share of placental oxygen and glucose consumption. We speculate that this response preserves glucose and oxygen for transfer to the fetus during the stressful events of labor. PMID:25454472

  14. Signaling in large-scale neural networks

    DEFF Research Database (Denmark)

    Berg, Rune W; Hounsgaard, Jørn

    2009-01-01

    We examine the recent finding that neurons in spinal motor circuits enter a high conductance state during functional network activity. The underlying concomitant increase in random inhibitory and excitatory synaptic activity leads to stochastic signal processing. The possible advantages of this m......We examine the recent finding that neurons in spinal motor circuits enter a high conductance state during functional network activity. The underlying concomitant increase in random inhibitory and excitatory synaptic activity leads to stochastic signal processing. The possible advantages...... of this metabolically costly organization are analyzed by comparing with synaptically less intense networks driven by the intrinsic response properties of the network neurons....

  15. Assembly and control of large microtubule complexes

    Science.gov (United States)

    Korolev, Kirill; Ishihara, Keisuke; Mitchison, Timothy

    Motility, division, and other cellular processes require rapid assembly and disassembly of microtubule structures. We report a new mechanism for the formation of asters, radial microtubule complexes found in very large cells. The standard model of aster growth assumes elongation of a fixed number of microtubules originating from the centrosomes. However, aster morphology in this model does not scale with cell size, and we found evidence for microtubule nucleation away from centrosomes. By combining polymerization dynamics and auto-catalytic nucleation of microtubules, we developed a new biophysical model of aster growth. The model predicts an explosive transition from an aster with a steady-state radius to one that expands as a travelling wave. At the transition, microtubule density increases continuously, but aster growth rate discontinuously jumps to a nonzero value. We tested our model with biochemical perturbations in egg extract and confirmed main theoretical predictions including the jump in the growth rate. Our results show that asters can grow even though individual microtubules are short and unstable. The dynamic balance between microtubule collapse and nucleation could be a general framework for the assembly and control of large microtubule complexes. NIH GM39565; Simons Foundation 409704; Honjo International 486 Scholarship Foundation.

  16. Heavy neutrino signals at large hadron colliders

    International Nuclear Information System (INIS)

    Aguila, Francisco del; Aguilar-Saavedra, Juan Antonio; Pittau, Roberto

    2007-01-01

    We study the LHC discovery potential for heavy Majorana neutrino singlets in the process pp → W + → l + N → l + l + jj (l = e, μ) plus its charge conjugate. With a fast detector simulation we show that backgrounds involving two like-sign charged leptons are not negligible and, moreover, they cannot be eliminated with simple sequential kinematical cuts. Using a likelihood analysis it is shown that, for heavy neutrinos coupling only to the muon, LHC has 5σ sensitivity for masses up to 200 GeV in the final state μ ± μ ± jj. This reduction in sensitivity, compared to previous parton-level estimates, is driven by the ∼ 10 2 -10 3 times larger background. Limits are also provided for e ± e ± jj and e ± μ ± jj final states, as well as for Tevatron. For heavy Dirac neutrinos the prospects are worse because backgrounds involving two opposite charge leptons are much larger. For this case, we study the observability of the lepton flavour violating signal e ± μ -+ jj. As a by-product of our analysis, heavy neutrino production has been implemented within the ALPGEN framework

  17. Biomagnetic Signals of the Large Intestine

    International Nuclear Information System (INIS)

    Cordova, T.; Sosa, M.; Bradshaw, L. A.; Adilton, A.

    2008-01-01

    Large intestine is part of the gastrointestinal tract with an average length, in adults, of 1.5 m. The gold standard technique in clinical medicine is the colonoscopy. Nevertheless, other techniques are capable of presenting information on physiological processes which take place in this part of the gastrointestinal system. Three recent studies are discussed in this paper in order to make this information more widely available. The authors consider that the biomagnetic technique could be easily implemented in hospitals around the world. Options will be available for research and clinical medicine

  18. TESLA: Large Signal Simulation Code for Klystrons

    International Nuclear Information System (INIS)

    Vlasov, Alexander N.; Cooke, Simon J.; Chernin, David P.; Antonsen, Thomas M. Jr.; Nguyen, Khanh T.; Levush, Baruch

    2003-01-01

    TESLA (Telegraphist's Equations Solution for Linear Beam Amplifiers) is a new code designed to simulate linear beam vacuum electronic devices with cavities, such as klystrons, extended interaction klystrons, twistrons, and coupled cavity amplifiers. The model includes a self-consistent, nonlinear solution of the three-dimensional electron equations of motion and the solution of time-dependent field equations. The model differs from the conventional Particle in Cell approach in that the field spectrum is assumed to consist of a carrier frequency and its harmonics with slowly varying envelopes. Also, fields in the external cavities are modeled with circuit like equations and couple to fields in the beam region through boundary conditions on the beam tunnel wall. The model in TESLA is an extension of the model used in gyrotron code MAGY. The TESLA formulation has been extended to be capable to treat the multiple beam case, in which each beam is transported inside its own tunnel. The beams interact with each other as they pass through the gaps in their common cavities. The interaction is treated by modification of the boundary conditions on the wall of each tunnel to include the effect of adjacent beams as well as the fields excited in each cavity. The extended version of TESLA for the multiple beam case, TESLA-MB, has been developed for single processor machines, and can run on UNIX machines and on PC computers with a large memory (above 2GB). The TESLA-MB algorithm is currently being modified to simulate multiple beam klystrons on multiprocessor machines using the MPI (Message Passing Interface) environment. The code TESLA has been verified by comparison with MAGIC for single and multiple beam cases. The TESLA code and the MAGIC code predict the same power within 1% for a simple two cavity klystron design while the computational time for TESLA is orders of magnitude less than for MAGIC 2D. In addition, recently TESLA was used to model the L-6048 klystron, code

  19. Entropy for the Complexity of Physiological Signal Dynamics.

    Science.gov (United States)

    Zhang, Xiaohua Douglas

    2017-01-01

    Recently, the rapid development of large data storage technologies, mobile network technology, and portable medical devices makes it possible to measure, record, store, and track analysis of biological dynamics. Portable noninvasive medical devices are crucial to capture individual characteristics of biological dynamics. The wearable noninvasive medical devices and the analysis/management of related digital medical data will revolutionize the management and treatment of diseases, subsequently resulting in the establishment of a new healthcare system. One of the key features that can be extracted from the data obtained by wearable noninvasive medical device is the complexity of physiological signals, which can be represented by entropy of biological dynamics contained in the physiological signals measured by these continuous monitoring medical devices. Thus, in this chapter I present the major concepts of entropy that are commonly used to measure the complexity of biological dynamics. The concepts include Shannon entropy, Kolmogorov entropy, Renyi entropy, approximate entropy, sample entropy, and multiscale entropy. I also demonstrate an example of using entropy for the complexity of glucose dynamics.

  20. Surgical Treatment of a Large Complex Odontoma

    Directory of Open Access Journals (Sweden)

    Burak Cezairli

    2017-08-01

    Full Text Available The treatment modalities for odontomas are generally depend on the tumors size. Small and medium lesions can usually be removed easily allowing preservation of surrounding anatomical structures. In our study, we reported a conservative surgical treatment of a large complex odontoma. A 19-year-old woman was referred to our clinic after an incidentally observed lesion on her right mandibular angle. The patient was symptom-free at the time of visit. Computed tomography (CT images showed a mass with a size of 3.5 cm x 3 cm x 2 cm. CT sections and tridimensional images showed partially eroded buccal and lingual cortex. Surgical treatment was indicated with an initial diagnosis of compound odontoma. The lesion removed after sectioning with bur and maxillo-mandibular fixation (MMF were not thought to be necessary while the buccal and lingual cortexes were mostly reliable for preventing a fracture. In our case, the size of the odontoma was suitable for a conservative treatment method and with this modality we managed to prevent a possible fracture and eliminate the disadvantages of MMF.

  1. Sequence distance via parsing complexity: Heartbeat signals

    International Nuclear Information System (INIS)

    Degli Esposti, M.; Farinelli, C.; Menconi, G.

    2009-01-01

    We compare and discuss the use of different symbolic codings of electrocardiogram (ECG) signals in order to distinguish healthy patients from hospitalized ones. To this aim, we recall a parsing-based similarity distance and compare the performances of several methods of classification of data.

  2. Large-signal modeling method for power FETs and diodes

    Energy Technology Data Exchange (ETDEWEB)

    Sun Lu; Wang Jiali; Wang Shan; Li Xuezheng; Shi Hui; Wang Na; Guo Shengping, E-mail: sunlu_1019@126.co [School of Electromechanical Engineering, Xidian University, Xi' an 710071 (China)

    2009-06-01

    Under a large signal drive level, a frequency domain black box model of the nonlinear scattering function is introduced into power FETs and diodes. A time domain measurement system and a calibration method based on a digital oscilloscope are designed to extract the nonlinear scattering function of semiconductor devices. The extracted models can reflect the real electrical performance of semiconductor devices and propose a new large-signal model to the design of microwave semiconductor circuits.

  3. Large-signal modeling method for power FETs and diodes

    International Nuclear Information System (INIS)

    Sun Lu; Wang Jiali; Wang Shan; Li Xuezheng; Shi Hui; Wang Na; Guo Shengping

    2009-01-01

    Under a large signal drive level, a frequency domain black box model of the nonlinear scattering function is introduced into power FETs and diodes. A time domain measurement system and a calibration method based on a digital oscilloscope are designed to extract the nonlinear scattering function of semiconductor devices. The extracted models can reflect the real electrical performance of semiconductor devices and propose a new large-signal model to the design of microwave semiconductor circuits.

  4. Selective disruption of the AKAP signaling complexes.

    Science.gov (United States)

    Kennedy, Eileen J; Scott, John D

    2015-01-01

    Synthesis of the second messenger cAMP activates a variety of signaling pathways critical for all facets of intracellular regulation. Protein kinase A (PKA) is the major cAMP-responsive effector. Where and when this enzyme is activated has profound implications on the cellular role of PKA. A-Kinase Anchoring Proteins (AKAPs) play a critical role in this process by orchestrating spatial and temporal aspects of PKA action. A popular means of evaluating the impact of these anchored signaling events is to biochemically interfere with the PKA-AKAP interface. Hence, peptide disruptors of PKA anchoring are valuable tools in the investigation of local PKA action. This article outlines the development of PKA isoform-selective disruptor peptides, documents the optimization of cell-soluble peptide derivatives, and introduces alternative cell-based approaches that interrogate other aspects of the PKA-AKAP interface.

  5. Astrocyte Ca2+ signalling: an unexpected complexity

    OpenAIRE

    Volterra, Andrea; Liaudet, Nicolas; Savtchouk, Iaroslav

    2014-01-01

    Astrocyte Ca(2+) signalling has been proposed to link neuronal information in different spatial-temporal dimensions to achieve a higher level of brain integration. However, some discrepancies in the results of recent studies challenge this view and highlight key insufficiencies in our current understanding. In parallel, new experimental approaches that enable the study of astrocyte physiology at higher spatial-temporal resolution in intact brain preparations are beginning to reveal an unexpec...

  6. Modulation of EEG Theta Band Signal Complexity by Music Therapy

    Science.gov (United States)

    Bhattacharya, Joydeep; Lee, Eun-Jeong

    The primary goal of this study was to investigate the impact of monochord (MC) sounds, a type of archaic sounds used in music therapy, on the neural complexity of EEG signals obtained from patients undergoing chemotherapy. The secondary goal was to compare the EEG signal complexity values for monochords with those for progressive muscle relaxation (PMR), an alternative therapy for relaxation. Forty cancer patients were randomly allocated to one of the two relaxation groups, MC and PMR, over a period of six months; continuous EEG signals were recorded during the first and last sessions. EEG signals were analyzed by applying signal mode complexity, a measure of complexity of neuronal oscillations. Across sessions, both groups showed a modulation of complexity of beta-2 band (20-29Hz) at midfrontal regions, but only MC group showed a modulation of complexity of theta band (3.5-7.5Hz) at posterior regions. Therefore, the neuronal complexity patterns showed different changes in EEG frequency band specific complexity resulting in two different types of interventions. Moreover, the different neural responses to listening to monochords and PMR were observed after regular relaxation interventions over a short time span.

  7. Brain signal complexity rises with repetition suppression in visual learning.

    Science.gov (United States)

    Lafontaine, Marc Philippe; Lacourse, Karine; Lina, Jean-Marc; McIntosh, Anthony R; Gosselin, Frédéric; Théoret, Hugo; Lippé, Sarah

    2016-06-21

    Neuronal activity associated with visual processing of an unfamiliar face gradually diminishes when it is viewed repeatedly. This process, known as repetition suppression (RS), is involved in the acquisition of familiarity. Current models suggest that RS results from interactions between visual information processing areas located in the occipito-temporal cortex and higher order areas, such as the dorsolateral prefrontal cortex (DLPFC). Brain signal complexity, which reflects information dynamics of cortical networks, has been shown to increase as unfamiliar faces become familiar. However, the complementarity of RS and increases in brain signal complexity have yet to be demonstrated within the same measurements. We hypothesized that RS and brain signal complexity increase occur simultaneously during learning of unfamiliar faces. Further, we expected alteration of DLPFC function by transcranial direct current stimulation (tDCS) to modulate RS and brain signal complexity over the occipito-temporal cortex. Participants underwent three tDCS conditions in random order: right anodal/left cathodal, right cathodal/left anodal and sham. Following tDCS, participants learned unfamiliar faces, while an electroencephalogram (EEG) was recorded. Results revealed RS over occipito-temporal electrode sites during learning, reflected by a decrease in signal energy, a measure of amplitude. Simultaneously, as signal energy decreased, brain signal complexity, as estimated with multiscale entropy (MSE), increased. In addition, prefrontal tDCS modulated brain signal complexity over the right occipito-temporal cortex during the first presentation of faces. These results suggest that although RS may reflect a brain mechanism essential to learning, complementary processes reflected by increases in brain signal complexity, may be instrumental in the acquisition of novel visual information. Such processes likely involve long-range coordinated activity between prefrontal and lower order visual

  8. Large-signal stability analysis of PWM converters

    Energy Technology Data Exchange (ETDEWEB)

    Huynh, P.T. [Philips Labs., Briarcliff Manor, NY (United States); Cho, B.H. [Seoul National Univ. (Korea, Republic of). Dept. of Electrical Engineering

    1995-12-31

    Investigation of the effects of existing nonlinearities on the stability of PWM converters is performed. The bilinear structure, the duty cycle saturation, and the opamp saturation are the principal nonlinearities in PWM converters. These nonlinearities are incorporated in the large-signal analytical models of PWM converters, and the basic input-output stability theory is applied to analyze their stability. Design and optimization of the small-signal loop gains to counteract the undesirable nonlinear effects are also discussed.

  9. An accurate and simple large signal model of HEMT

    DEFF Research Database (Denmark)

    Liu, Qing

    1989-01-01

    A large-signal model of discrete HEMTs (high-electron-mobility transistors) has been developed. It is simple and suitable for SPICE simulation of hybrid digital ICs. The model parameters are extracted by using computer programs and data provided by the manufacturer. Based on this model, a hybrid...

  10. Measurement of MOSFET LF Noise Under Large Signal RF Excitation

    NARCIS (Netherlands)

    van der Wel, A.P.; Klumperink, Eric A.M.; Nauta, Bram

    A new measurement technique is presented that allows measurement of MOSFET LF noise under large signal RF excitation. Measurements indicate that MOSFETS exhibit a reduction in LF noise when they are cycled from inversion to accummulation and that this reduction does not depend on the frequency of

  11. Large signal simulation of photonic crystal Fano laser

    DEFF Research Database (Denmark)

    Zali, Aref Rasoulzadeh; Yu, Yi; Moravvej-Farshi, Mohammad Kazem

    2017-01-01

    be modulated at frequencies exceeding 1 THz which is much higher than its corresponding relaxation oscillation frequency. Large signal simulation of the Fano laser is also investigated based on pseudorandom bit sequence at 0.5 Tbit/s. It shows eye patterns are open at such high modulation frequency, verifying...

  12. Large-Signal Code TESLA: Current Status and Recent Development

    National Research Council Canada - National Science Library

    Chernyavskiy, Igor A; Vlasov, Alexander N; Cooke, Simon J; Abe, David K; Levush, Baruch; Antonsen, Jr., Thomas M; Nguyen, Khanh T

    2008-01-01

    .... One such tool is the large-signal code TESLA, which was successfully applied for the modeling of single-beam and multiple-beam klystron devices at the Naval Research Laboratory and which is now used by number of U.S. companies...

  13. Fractal Complexity-Based Feature Extraction Algorithm of Communication Signals

    Science.gov (United States)

    Wang, Hui; Li, Jingchao; Guo, Lili; Dou, Zheng; Lin, Yun; Zhou, Ruolin

    How to analyze and identify the characteristics of radiation sources and estimate the threat level by means of detecting, intercepting and locating has been the central issue of electronic support in the electronic warfare, and communication signal recognition is one of the key points to solve this issue. Aiming at accurately extracting the individual characteristics of the radiation source for the increasingly complex communication electromagnetic environment, a novel feature extraction algorithm for individual characteristics of the communication radiation source based on the fractal complexity of the signal is proposed. According to the complexity of the received signal and the situation of environmental noise, use the fractal dimension characteristics of different complexity to depict the subtle characteristics of the signal to establish the characteristic database, and then identify different broadcasting station by gray relation theory system. The simulation results demonstrate that the algorithm can achieve recognition rate of 94% even in the environment with SNR of -10dB, and this provides an important theoretical basis for the accurate identification of the subtle features of the signal at low SNR in the field of information confrontation.

  14. Nonlinear complexity analysis of brain FMRI signals in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Moses O Sokunbi

    Full Text Available We investigated the differences in brain fMRI signal complexity in patients with schizophrenia while performing the Cyberball social exclusion task, using measures of Sample entropy and Hurst exponent (H. 13 patients meeting diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM IV criteria for schizophrenia and 16 healthy controls underwent fMRI scanning at 1.5 T. The fMRI data of both groups of participants were pre-processed, the entropy characterized and the Hurst exponent extracted. Whole brain entropy and H maps of the groups were generated and analysed. The results after adjusting for age and sex differences together show that patients with schizophrenia exhibited higher complexity than healthy controls, at mean whole brain and regional levels. Also, both Sample entropy and Hurst exponent agree that patients with schizophrenia have more complex fMRI signals than healthy controls. These results suggest that schizophrenia is associated with more complex signal patterns when compared to healthy controls, supporting the increase in complexity hypothesis, where system complexity increases with age or disease, and also consistent with the notion that schizophrenia is characterised by a dysregulation of the nonlinear dynamics of underlying neuronal systems.

  15. Aliasing in the Complex Cepstrum of Linear-Phase Signals

    DEFF Research Database (Denmark)

    Bysted, Tommy Kristensen

    1997-01-01

    Assuming linear-phase of the associated time signal, this paper presents an approximated analytical description of the unavoidable aliasing in practical use of complex cepstrums. The linear-phase assumption covers two major applications of complex cepstrums which are linear- to minimum-phase FIR......-filter transformation and minimum-phase estimation from amplitude specifications. The description is made in the cepstrum domain, the Fourier transform of the complex cepstrum and in the frequency domain. Two examples are given, one for verification of the derived equations and one using the description to reduce...... aliasing in minimum-phase estimation...

  16. Unusually large erupted complex odontoma: A rare case report

    Energy Technology Data Exchange (ETDEWEB)

    Bagewadi, Shivanand B.; Kukreja, Rahul; Suma, Gundareddy N.; Yadav, Bhawn; Sharma, Havi [Dept. of Oral Medicine and Radiology, ITS Centre for Dental Studies and Research, Murad Nagar (India)

    2015-03-15

    Odontomas are nonaggressive, hamartomatous developmental malformations composed of mature tooth substances and may be compound or complex depending on the extent of morphodifferentiation or on their resemblance to normal teeth. Among them, complex odontomas are relatively rare tumors. They are usually asymptomatic in nature. Occasionally, these tumors become large, causing bone expansion followed by facial asymmetry. Odontoma eruptions are uncommon, and thus far, very few cases of erupted complex odontomas have been reported in the literature. Here, we report the case of an unusually large, painless, complex odontoma located in the right posterior mandible.

  17. Mixed-signal instrumentation for large-signal device characterization and modelling

    NARCIS (Netherlands)

    Marchetti, M.

    2013-01-01

    This thesis concentrates on the development of advanced large-signal measurement and characterization tools to support technology development, model extraction and validation, and power amplifier (PA) designs that address the newly introduced third and fourth generation (3G and 4G) wideband

  18. Using lanthanoid complexes to phase large macromolecular assemblies

    International Nuclear Information System (INIS)

    Talon, Romain; Kahn, Richard; Durá, M. Asunción; Maury, Olivier; Vellieux, Frédéric M. D.; Franzetti, Bruno; Girard, Eric

    2011-01-01

    A lanthanoid complex, [Eu(DPA) 3 ] 3− , was used to obtain experimental phases at 4.0 Å resolution of PhTET1-12s, a large self-compartmentalized homo-dodecameric protease complex of 444 kDa. Lanthanoid ions exhibit extremely large anomalous X-ray scattering at their L III absorption edge. They are thus well suited for anomalous diffraction experiments. A novel class of lanthanoid complexes has been developed that combines the physical properties of lanthanoid atoms with functional chemical groups that allow non-covalent binding to proteins. Two structures of large multimeric proteins have already been determined by using such complexes. Here the use of the luminescent europium tris-dipicolinate complex [Eu(DPA) 3 ] 3− to solve the low-resolution structure of a 444 kDa homododecameric aminopeptidase, called PhTET1-12s from the archaea Pyrococcus horikoshii, is reported. Surprisingly, considering the low resolution of the data, the experimental electron density map is very well defined. Experimental phases obtained by using the lanthanoid complex lead to maps displaying particular structural features usually observed in higher-resolution maps. Such complexes open a new way for solving the structure of large molecular assemblies, even with low-resolution data

  19. Assembly of Oligomeric Death Domain Complexes during Toll Receptor Signaling*

    OpenAIRE

    Moncrieffe, Martin C.; Grossmann, J. Günter; Gay, Nicholas J.

    2008-01-01

    The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show ...

  20. Research and assessment of competitiveness of large engineering complexes

    Directory of Open Access Journals (Sweden)

    Krivorotov V.V.

    2017-01-01

    Full Text Available The urgency of the problem of ensuring the competitiveness of manufacturing and high-tech sectors is shown. Substantiated the decisive role of the large industrial complexes in the formation of the results of the national economy; the author’s interpretation of the concept of “industrial complex” with regard to current economic systems. Current approaches to assessing the competitiveness of enterprises and industrial complexes are analyzed; showing their main advantages and disadvantages. Provides scientific-methodological approach to the study and management of competitiveness of a large industrial complex; the description of its main units is provided. As a Central element of the scientific methodology approach proposed the methodology for assessing the competitiveness of a large industrial complex based on the Pattern-method; a modular system of indicators of competitiveness is developed and its adaptation to a large engineering complexes is made. Using the developed methodology the competitiveness of one of the largest engineering complexes of the group of companies Uralelectrotyazhmash, which is the leading enterprises in electrotechnical industry of Russia is assessed. The evaluation identified the main problems and bottlenecks in the development of these enterprises, and their comparison with leading competitors is provided. According to the results of the study the main conclusions and recommendations are formed.

  1. Assembly of Oligomeric Death Domain Complexes during Toll Receptor Signaling*

    Science.gov (United States)

    Moncrieffe, Martin C.; Grossmann, J. Günter; Gay, Nicholas J.

    2008-01-01

    The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show that both the heterodimeric and heterotrimeric complexes form kidney-shaped structures and that Tube is bivalent and has separate high affinity binding sites for dMyD88 and Pelle. Additionally we found no interaction between the isolated death domains of Pelle and dMyD88. These results indicate that the mode of assembly of the heterotrimeric dMyD88-Tube-Pelle complex downstream of the activated Toll receptor is unique. The measured dissociation constants for the interaction between the death domains of dMyD88 and Tube and of Pelle and a preformed dMyD88-Tube complex are used to propose a model of the early postreceptor events in Drosophila Toll receptor signaling. PMID:18829464

  2. Assembly of oligomeric death domain complexes during Toll receptor signaling.

    Science.gov (United States)

    Moncrieffe, Martin C; Grossmann, J Günter; Gay, Nicholas J

    2008-11-28

    The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show that both the heterodimeric and heterotrimeric complexes form kidney-shaped structures and that Tube is bivalent and has separate high affinity binding sites for dMyD88 and Pelle. Additionally we found no interaction between the isolated death domains of Pelle and dMyD88. These results indicate that the mode of assembly of the heterotrimeric dMyD88-Tube-Pelle complex downstream of the activated Toll receptor is unique. The measured dissociation constants for the interaction between the death domains of dMyD88 and Tube and of Pelle and a preformed dMyD88-Tube complex are used to propose a model of the early postreceptor events in Drosophila Toll receptor signaling.

  3. Simulation of Weak Signals of Nanotechnology Innovation in Complex System

    Directory of Open Access Journals (Sweden)

    Sun Hi Yoo

    2018-02-01

    Full Text Available It is especially indispensable for new businesses or industries to predict the innovation of new technologies. This requires an understanding of how the complex process of innovation, which is accomplished through more efficient products, processes, services, technologies, or ideas, is adopted and diffused in the market, government, and society. Furthermore, detecting “weak signals” (signs of change in science and technology (S&T is also important to foretell events associated with innovations in technology. Thus, we explore the dynamic behavior of weak signals of a specific technological innovation using the agent-based simulating tool NetLogo. This study provides a deeper understanding of the early stages of complex technology innovation, and the models are capable of analyzing initial complex interaction structures between components of technologies and between agents engaged in collective invention.

  4. An improved large signal model of InP HEMTs

    Science.gov (United States)

    Li, Tianhao; Li, Wenjun; Liu, Jun

    2018-05-01

    An improved large signal model for InP HEMTs is proposed in this paper. The channel current and charge model equations are constructed based on the Angelov model equations. Both the equations for channel current and gate charge models were all continuous and high order drivable, and the proposed gate charge model satisfied the charge conservation. For the strong leakage induced barrier reduction effect of InP HEMTs, the Angelov current model equations are improved. The channel current model could fit DC performance of devices. A 2 × 25 μm × 70 nm InP HEMT device is used to demonstrate the extraction and validation of the model, in which the model has predicted the DC I–V, C–V and bias related S parameters accurately. Project supported by the National Natural Science Foundation of China (No. 61331006).

  5. Large-Signal DG-MOSFET Modelling for RFID Rectification

    Directory of Open Access Journals (Sweden)

    R. Rodríguez

    2016-01-01

    Full Text Available This paper analyses the undoped DG-MOSFETs capability for the operation of rectifiers for RFIDs and Wireless Power Transmission (WPT at microwave frequencies. For this purpose, a large-signal compact model has been developed and implemented in Verilog-A. The model has been numerically validated with a device simulator (Sentaurus. It is found that the number of stages to achieve the optimal rectifier performance is inferior to that required with conventional MOSFETs. In addition, the DC output voltage could be incremented with the use of appropriate mid-gap metals for the gate, as TiN. Minor impact of short channel effects (SCEs on rectification is also pointed out.

  6. Management of Large Erupting Complex Odontoma in Maxilla

    Directory of Open Access Journals (Sweden)

    Colm Murphy

    2014-01-01

    Full Text Available We present the unusual case of a large complex odontoma erupting in the maxilla. Odontomas are benign developmental tumours of odontogenic origin. They are characterized by slow growth and nonaggressive behaviour. Complex odontomas, which erupt, are rare. They are usually asymptomatic and are identified on routine radiograph but may present with erosion into the oral cavity with subsequent cellulitis and facial asymmetry. This present paper describes the presentation and management of an erupting complex odontoma, occupying the maxillary sinus with extension to the infraorbital rim. We also discuss various surgical approaches used to access this anatomic area.

  7. Large-scale computing techniques for complex system simulations

    CERN Document Server

    Dubitzky, Werner; Schott, Bernard

    2012-01-01

    Complex systems modeling and simulation approaches are being adopted in a growing number of sectors, including finance, economics, biology, astronomy, and many more. Technologies ranging from distributed computing to specialized hardware are explored and developed to address the computational requirements arising in complex systems simulations. The aim of this book is to present a representative overview of contemporary large-scale computing technologies in the context of complex systems simulations applications. The intention is to identify new research directions in this field and

  8. Structuring and assessing large and complex decision problems using MCDA

    DEFF Research Database (Denmark)

    Barfod, Michael Bruhn

    This paper presents an approach for the structuring and assessing of large and complex decision problems using multi-criteria decision analysis (MCDA). The MCDA problem is structured in a decision tree and assessed using the REMBRANDT technique featuring a procedure for limiting the number of pair...

  9. Complex Interplay of Hormonal Signals during Grape Berry Ripening

    Directory of Open Access Journals (Sweden)

    Ana Margarida Fortes

    2015-05-01

    Full Text Available Grape and wine production and quality is extremely dependent on the fruit ripening process. Sensory and nutritional characteristics are important aspects for consumers and their development during fruit ripening involves complex hormonal control. In this review, we explored data already published on grape ripening and compared it with the hormonal regulation of ripening of other climacteric and non-climacteric fruits. The roles of abscisic acid, ethylene, and brassinosteroids as promoters of ripening are discussed, as well as the role of auxins, cytokinins, gibberellins, jasmonates, and polyamines as inhibitors of ripening. In particular, the recently described role of polyamine catabolism in grape ripening is discussed, together with its putative interaction with other hormones. Furthermore, other recent examples of cross-talk among the different hormones are presented, revealing a complex interplay of signals during grape development and ripening.

  10. Design principles of nuclear receptor signaling: how complex networking improves signal transduction

    Science.gov (United States)

    Kolodkin, Alexey N; Bruggeman, Frank J; Plant, Nick; Moné, Martijn J; Bakker, Barbara M; Campbell, Moray J; van Leeuwen, Johannes P T M; Carlberg, Carsten; Snoep, Jacky L; Westerhoff, Hans V

    2010-01-01

    The topology of nuclear receptor (NR) signaling is captured in a systems biological graphical notation. This enables us to identify a number of ‘design' aspects of the topology of these networks that might appear unnecessarily complex or even functionally paradoxical. In realistic kinetic models of increasing complexity, calculations show how these features correspond to potentially important design principles, e.g.: (i) cytosolic ‘nuclear' receptor may shuttle signal molecules to the nucleus, (ii) the active export of NRs may ensure that there is sufficient receptor protein to capture ligand at the cytoplasmic membrane, (iii) a three conveyor belts design dissipating GTP-free energy, greatly aids response, (iv) the active export of importins may prevent sequestration of NRs by importins in the nucleus and (v) the unspecific nature of the nuclear pore may ensure signal-flux robustness. In addition, the models developed are suitable for implementation in specific cases of NR-mediated signaling, to predict individual receptor functions and differential sensitivity toward physiological and pharmacological ligands. PMID:21179018

  11. Association between increased EEG signal complexity and cannabis dependence.

    Science.gov (United States)

    Laprevote, Vincent; Bon, Laura; Krieg, Julien; Schwitzer, Thomas; Bourion-Bedes, Stéphanie; Maillard, Louis; Schwan, Raymund

    2017-12-01

    Both acute and regular cannabis use affects the functioning of the brain. While several studies have demonstrated that regular cannabis use can impair the capacity to synchronize neural assemblies during specific tasks, less is known about spontaneous brain activity. This can be explored by measuring EEG complexity, which reflects the spontaneous variability of human brain activity. A recent study has shown that acute cannabis use can affect that complexity. Since the characteristics of cannabis use can affect the impact on brain functioning, this study sets out to measure EEG complexity in regular cannabis users with or without dependence, in comparison with healthy controls. We recruited 26 healthy controls, 25 cannabis users without cannabis dependence and 14 cannabis users with cannabis dependence, based on DSM IV TR criteria. The EEG signal was extracted from at least 250 epochs of the 500ms pre-stimulation phase during a visual evoked potential paradigm. Brain complexity was estimated using Lempel-Ziv Complexity (LZC), which was compared across groups by non-parametric Kruskall-Wallis ANOVA. The analysis revealed a significant difference between the groups, with higher LZC in participants with cannabis dependence than in non-dependent cannabis users. There was no specific localization of this effect across electrodes. We showed that cannabis dependence is associated to an increased spontaneous brain complexity in regular users. This result is in line with previous results in acute cannabis users. It may reflect increased randomness of neural activity in cannabis dependence. Future studies should explore whether this effect is permanent or diminishes with cannabis cessation. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  12. Age-Related Changes in Electroencephalographic Signal Complexity

    Science.gov (United States)

    Zappasodi, Filippo; Marzetti, Laura; Olejarczyk, Elzbieta; Tecchio, Franca; Pizzella, Vittorio

    2015-01-01

    The study of active and healthy aging is a primary focus for social and neuroscientific communities. Here, we move a step forward in assessing electrophysiological neuronal activity changes in the brain with healthy aging. To this end, electroencephalographic (EEG) resting state activity was acquired in 40 healthy subjects (age 16–85). We evaluated Fractal Dimension (FD) according to the Higuchi algorithm, a measure which quantifies the presence of statistical similarity at different scales in temporal fluctuations of EEG signals. Our results showed that FD increases from age twenty to age fifty and then decreases. The curve that best fits the changes in FD values across age over the whole sample is a parabola, with the vertex located around age fifty. Moreover, FD changes are site specific, with interhemispheric FD asymmetry being pronounced in elderly individuals in the frontal and central regions. The present results indicate that fractal dimension well describes the modulations of brain activity with age. Since fractal dimension has been proposed to be related to the complexity of the signal dynamics, our data demonstrate that the complexity of neuronal electric activity changes across the life span of an individual, with a steady increase during young adulthood and a decrease in the elderly population. PMID:26536036

  13. Enabling complex genetic circuits to respond to extrinsic environmental signals.

    Science.gov (United States)

    Hoynes-O'Connor, Allison; Shopera, Tatenda; Hinman, Kristina; Creamer, John Philip; Moon, Tae Seok

    2017-07-01

    Genetic circuits have the potential to improve a broad range of metabolic engineering processes and address a variety of medical and environmental challenges. However, in order to engineer genetic circuits that can meet the needs of these real-world applications, genetic sensors that respond to relevant extrinsic and intrinsic signals must be implemented in complex genetic circuits. In this work, we construct the first AND and NAND gates that respond to temperature and pH, two signals that have relevance in a variety of real-world applications. A previously identified pH-responsive promoter and a temperature-responsive promoter were extracted from the E. coli genome, characterized, and modified to suit the needs of the genetic circuits. These promoters were combined with components of the type III secretion system in Salmonella typhimurium and used to construct a set of AND gates with up to 23-fold change. Next, an antisense RNA was integrated into the circuit architecture to invert the logic of the AND gate and generate a set of NAND gates with up to 1168-fold change. These circuits provide the first demonstration of complex pH- and temperature-responsive genetic circuits, and lay the groundwork for the use of similar circuits in real-world applications. Biotechnol. Bioeng. 2017;114: 1626-1631. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Stochastic effects as a force to increase the complexity of signaling networks

    KAUST Repository

    Kuwahara, Hiroyuki

    2013-07-29

    Cellular signaling networks are complex and appear to include many nonfunctional elements. Recently, it was suggested that nonfunctional interactions of proteins cause signaling noise, which, perhaps, shapes the signal transduction mechanism. However, the conditions under which molecular noise influences cellular information processing remain unclear. Here, we explore a large number of simple biological models of varying network sizes to understand the architectural conditions under which the interactions of signaling proteins can exhibit specific stochastic effects - called deviant effects - in which the average behavior of a biological system is substantially altered in the presence of molecular noise. We find that a small fraction of these networks does exhibit deviant effects and shares a common architectural feature whereas most of the networks show only insignificant levels of deviations. Interestingly, addition of seemingly unimportant interactions into protein networks gives rise to deviant effects.

  15. Weak signal transmission in complex networks and its application in detecting connectivity.

    Science.gov (United States)

    Liang, Xiaoming; Liu, Zonghua; Li, Baowen

    2009-10-01

    We present a network model of coupled oscillators to study how a weak signal is transmitted in complex networks. Through both theoretical analysis and numerical simulations, we find that the response of other nodes to the weak signal decays exponentially with their topological distance to the signal source and the coupling strength between two neighboring nodes can be figured out by the responses. This finding can be conveniently used to detect the topology of unknown network, such as the degree distribution, clustering coefficient and community structure, etc., by repeatedly choosing different nodes as the signal source. Through four typical networks, i.e., the regular one dimensional, small world, random, and scale-free networks, we show that the features of network can be approximately given by investigating many fewer nodes than the network size, thus our approach to detect the topology of unknown network may be efficient in practical situations with large network size.

  16. Stochastic effects as a force to increase the complexity of signaling networks

    KAUST Repository

    Kuwahara, Hiroyuki; Gao, Xin

    2013-01-01

    Cellular signaling networks are complex and appear to include many nonfunctional elements. Recently, it was suggested that nonfunctional interactions of proteins cause signaling noise, which, perhaps, shapes the signal transduction mechanism

  17. Assembly of Slx4 signaling complexes behind DNA replication forks.

    Science.gov (United States)

    Balint, Attila; Kim, TaeHyung; Gallo, David; Cussiol, Jose Renato; Bastos de Oliveira, Francisco M; Yimit, Askar; Ou, Jiongwen; Nakato, Ryuichiro; Gurevich, Alexey; Shirahige, Katsuhiko; Smolka, Marcus B; Zhang, Zhaolei; Brown, Grant W

    2015-08-13

    Obstructions to replication fork progression, referred to collectively as DNA replication stress, challenge genome stability. In Saccharomyces cerevisiae, cells lacking RTT107 or SLX4 show genome instability and sensitivity to DNA replication stress and are defective in the completion of DNA replication during recovery from replication stress. We demonstrate that Slx4 is recruited to chromatin behind stressed replication forks, in a region that is spatially distinct from that occupied by the replication machinery. Slx4 complex formation is nucleated by Mec1 phosphorylation of histone H2A, which is recognized by the constitutive Slx4 binding partner Rtt107. Slx4 is essential for recruiting the Mec1 activator Dpb11 behind stressed replication forks, and Slx4 complexes are important for full activity of Mec1. We propose that Slx4 complexes promote robust checkpoint signaling by Mec1 by stably recruiting Dpb11 within a discrete domain behind the replication fork, during DNA replication stress. © 2015 The Authors.

  18. Risk Management and Uncertainty in Large Complex Public Projects

    DEFF Research Database (Denmark)

    Neerup Themsen, Tim; Harty, Chris; Tryggestad, Kjell

    Governmental actors worldwide are promoting risk management as a rational approach to man-age uncertainty and improve the abilities to deliver large complex projects according to budget, time plans, and pre-set project specifications: But what do we know about the effects of risk management...... on the abilities to meet such objectives? Using Callon’s (1998) twin notions of framing and overflowing we examine the implementation of risk management within the Dan-ish public sector and the effects this generated for the management of two large complex pro-jects. We show how the rational framing of risk...... management have generated unexpected costly outcomes such as: the undermining of the longer-term value and societal relevance of the built asset, the negligence of the wider range of uncertainties emerging during project processes, and constraining forms of knowledge. We also show how expert accountants play...

  19. Experimental industrial signal acquisition board in a large scientific device

    Science.gov (United States)

    Zeng, Xiangzhen; Ren, Bin

    2018-02-01

    In order to measure the industrial signal of neutrino experiment, a set of general-purpose industrial data acquisition board has been designed. It includes the function of switch signal input and output, and the function of analog signal input. The main components are signal isolation amplifier and filter circuit, ADC circuit, microcomputer systems and isolated communication interface circuit. Through the practical experiments, it shows that the system is flexible, reliable, convenient and economical, and the system has characters of high definition and strong anti-interference ability. Thus, the system fully meets the design requirements.

  20. Computational study of noise in a large signal transduction network

    Directory of Open Access Journals (Sweden)

    Ruohonen Keijo

    2011-06-01

    Full Text Available Abstract Background Biochemical systems are inherently noisy due to the discrete reaction events that occur in a random manner. Although noise is often perceived as a disturbing factor, the system might actually benefit from it. In order to understand the role of noise better, its quality must be studied in a quantitative manner. Computational analysis and modeling play an essential role in this demanding endeavor. Results We implemented a large nonlinear signal transduction network combining protein kinase C, mitogen-activated protein kinase, phospholipase A2, and β isoform of phospholipase C networks. We simulated the network in 300 different cellular volumes using the exact Gillespie stochastic simulation algorithm and analyzed the results in both the time and frequency domain. In order to perform simulations in a reasonable time, we used modern parallel computing techniques. The analysis revealed that time and frequency domain characteristics depend on the system volume. The simulation results also indicated that there are several kinds of noise processes in the network, all of them representing different kinds of low-frequency fluctuations. In the simulations, the power of noise decreased on all frequencies when the system volume was increased. Conclusions We concluded that basic frequency domain techniques can be applied to the analysis of simulation results produced by the Gillespie stochastic simulation algorithm. This approach is suited not only to the study of fluctuations but also to the study of pure noise processes. Noise seems to have an important role in biochemical systems and its properties can be numerically studied by simulating the reacting system in different cellular volumes. Parallel computing techniques make it possible to run massive simulations in hundreds of volumes and, as a result, accurate statistics can be obtained from computational studies.

  1. Blind identification and separation of complex-valued signals

    CERN Document Server

    Moreau, Eric

    2013-01-01

    Blind identification consists of estimating a multi-dimensional system only through the use of its output, and source separation, the blind estimation of the inverse of the system. Estimation is generally carried out using different statistics of the output. The authors of this book consider the blind identification and source separation problem in the complex-domain, where the available statistical properties are richer and include non-circularity of the sources - underlying components. They define identifiability conditions and present state-of-the-art algorithms that are based on algebraic methods as well as iterative algorithms based on maximum likelihood theory. Contents 1. Mathematical Preliminaries. 2. Estimation by Joint Diagonalization. 3. Maximum Likelihood ICA. About the Authors Eric Moreau is Professor of Electrical Engineering at the University of Toulon, France. His research interests concern statistical signal processing, high order statistics and matrix/tensor decompositions with applic...

  2. Dangerous mating systems: signal complexity, signal content and neural capacity in spiders.

    Science.gov (United States)

    Herberstein, M E; Wignall, A E; Hebets, E A; Schneider, J M

    2014-10-01

    Spiders are highly efficient predators in possession of exquisite sensory capacities for ambushing prey, combined with machinery for launching rapid and determined attacks. As a consequence, any sexually motivated approach carries a risk of ending up as prey rather than as a mate. Sexual selection has shaped courtship to effectively communicate the presence, identity, motivation and/or quality of potential mates, which help ameliorate these risks. Spiders communicate this information via several sensory channels, including mechanical (e.g. vibrational), visual and/or chemical, with examples of multimodal signalling beginning to emerge in the literature. The diverse environments that spiders inhabit have further shaped courtship content and form. While our understanding of spider neurobiology remains in its infancy, recent studies are highlighting the unique and considerable capacities of spiders to process and respond to complex sexual signals. As a result, the dangerous mating systems of spiders are providing important insights into how ecology shapes the evolution of communication systems, with future work offering the potential to link this complex communication with its neural processes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Large-Scale Optimization for Bayesian Inference in Complex Systems

    Energy Technology Data Exchange (ETDEWEB)

    Willcox, Karen [MIT; Marzouk, Youssef [MIT

    2013-11-12

    The SAGUARO (Scalable Algorithms for Groundwater Uncertainty Analysis and Robust Optimization) Project focused on the development of scalable numerical algorithms for large-scale Bayesian inversion in complex systems that capitalize on advances in large-scale simulation-based optimization and inversion methods. The project was a collaborative effort among MIT, the University of Texas at Austin, Georgia Institute of Technology, and Sandia National Laboratories. The research was directed in three complementary areas: efficient approximations of the Hessian operator, reductions in complexity of forward simulations via stochastic spectral approximations and model reduction, and employing large-scale optimization concepts to accelerate sampling. The MIT--Sandia component of the SAGUARO Project addressed the intractability of conventional sampling methods for large-scale statistical inverse problems by devising reduced-order models that are faithful to the full-order model over a wide range of parameter values; sampling then employs the reduced model rather than the full model, resulting in very large computational savings. Results indicate little effect on the computed posterior distribution. On the other hand, in the Texas--Georgia Tech component of the project, we retain the full-order model, but exploit inverse problem structure (adjoint-based gradients and partial Hessian information of the parameter-to-observation map) to implicitly extract lower dimensional information on the posterior distribution; this greatly speeds up sampling methods, so that fewer sampling points are needed. We can think of these two approaches as ``reduce then sample'' and ``sample then reduce.'' In fact, these two approaches are complementary, and can be used in conjunction with each other. Moreover, they both exploit deterministic inverse problem structure, in the form of adjoint-based gradient and Hessian information of the underlying parameter-to-observation map, to

  4. Contribution of Large Region Joint Associations to Complex Traits Genetics

    Science.gov (United States)

    Paré, Guillaume; Asma, Senay; Deng, Wei Q.

    2015-01-01

    A polygenic model of inheritance, whereby hundreds or thousands of weakly associated variants contribute to a trait’s heritability, has been proposed to underlie the genetic architecture of complex traits. However, relatively few genetic variants have been positively identified so far and they collectively explain only a small fraction of the predicted heritability. We hypothesized that joint association of multiple weakly associated variants over large chromosomal regions contributes to complex traits variance. Confirmation of such regional associations can help identify new loci and lead to a better understanding of known ones. To test this hypothesis, we first characterized the ability of commonly used genetic association models to identify large region joint associations. Through theoretical derivation and simulation, we showed that multivariate linear models where multiple SNPs are included as independent predictors have the most favorable association profile. Based on these results, we tested for large region association with height in 3,740 European participants from the Health and Retirement Study (HRS) study. Adjusting for SNPs with known association with height, we demonstrated clustering of weak associations (p = 2x10-4) in regions extending up to 433.0 Kb from known height loci. The contribution of regional associations to phenotypic variance was estimated at 0.172 (95% CI 0.063-0.279; p < 0.001), which compared favorably to 0.129 explained by known height variants. Conversely, we showed that suggestively associated regions are enriched for known height loci. To extend our findings to other traits, we also tested BMI, HDLc and CRP for large region associations, with consistent results for CRP. Our results demonstrate the presence of large region joint associations and suggest these can be used to pinpoint weakly associated SNPs. PMID:25856144

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

    Directory of Open Access Journals (Sweden)

    Philipp S Orekhov

    2015-10-01

    Full Text Available 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.

  6. Large Scale Emerging Properties from Non Hamiltonian Complex Systems

    Directory of Open Access Journals (Sweden)

    Marco Bianucci

    2017-06-01

    Full Text Available The concept of “large scale” depends obviously on the phenomenon we are interested in. For example, in the field of foundation of Thermodynamics from microscopic dynamics, the spatial and time large scales are order of fraction of millimetres and microseconds, respectively, or lesser, and are defined in relation to the spatial and time scales of the microscopic systems. In large scale oceanography or global climate dynamics problems the time scales of interest are order of thousands of kilometres, for space, and many years for time, and are compared to the local and daily/monthly times scales of atmosphere and ocean dynamics. In all the cases a Zwanzig projection approach is, at least in principle, an effective tool to obtain class of universal smooth “large scale” dynamics for few degrees of freedom of interest, starting from the complex dynamics of the whole (usually many degrees of freedom system. The projection approach leads to a very complex calculus with differential operators, that is drastically simplified when the basic dynamics of the system of interest is Hamiltonian, as it happens in Foundation of Thermodynamics problems. However, in geophysical Fluid Dynamics, Biology, and in most of the physical problems the building block fundamental equations of motions have a non Hamiltonian structure. Thus, to continue to apply the useful projection approach also in these cases, we exploit the generalization of the Hamiltonian formalism given by the Lie algebra of dissipative differential operators. In this way, we are able to analytically deal with the series of the differential operators stemming from the projection approach applied to these general cases. Then we shall apply this formalism to obtain some relevant results concerning the statistical properties of the El Niño Southern Oscillation (ENSO.

  7. Monitoring super-volcanoes: geophysical and geochemical signals at Yellowstone and other large caldera systems.

    Science.gov (United States)

    Lowenstern, Jacob B; Smith, Robert B; Hill, David P

    2006-08-15

    Earth's largest calderas form as the ground collapses during immense volcanic eruptions, when hundreds to thousands of cubic kilometres of magma are explosively withdrawn from the Earth's crust over a period of days to weeks. Continuing long after such great eruptions, the resulting calderas often exhibit pronounced unrest, with frequent earthquakes, alternating uplift and subsidence of the ground, and considerable heat and mass flux. Because many active and extinct calderas show evidence for repetition of large eruptions, such systems demand detailed scientific study and monitoring. Two calderas in North America, Yellowstone (Wyoming) and Long Valley (California), are in areas of youthful tectonic complexity. Scientists strive to understand the signals generated when tectonic, volcanic and hydrothermal (hot ground water) processes intersect. One obstacle to accurate forecasting of large volcanic events is humanity's lack of familiarity with the signals leading up to the largest class of volcanic eruptions. Accordingly, it may be difficult to recognize the difference between smaller and larger eruptions. To prepare ourselves and society, scientists must scrutinize a spectrum of volcanic signals and assess the many factors contributing to unrest and toward diverse modes of eruption.

  8. Low-Complexity Transmit Antenna Selection and Beamforming for Large-Scale MIMO Communications

    Directory of Open Access Journals (Sweden)

    Kun Qian

    2014-01-01

    Full Text Available Transmit antenna selection plays an important role in large-scale multiple-input multiple-output (MIMO communications, but optimal large-scale MIMO antenna selection is a technical challenge. Exhaustive search is often employed in antenna selection, but it cannot be efficiently implemented in large-scale MIMO communication systems due to its prohibitive high computation complexity. This paper proposes a low-complexity interactive multiple-parameter optimization method for joint transmit antenna selection and beamforming in large-scale MIMO communication systems. The objective is to jointly maximize the channel outrage capacity and signal-to-noise (SNR performance and minimize the mean square error in transmit antenna selection and minimum variance distortionless response (MVDR beamforming without exhaustive search. The effectiveness of all the proposed methods is verified by extensive simulation results. It is shown that the required antenna selection processing time of the proposed method does not increase along with the increase of selected antennas, but the computation complexity of conventional exhaustive search method will significantly increase when large-scale antennas are employed in the system. This is particularly useful in antenna selection for large-scale MIMO communication systems.

  9. Complex modular structure of large-scale brain networks

    Science.gov (United States)

    Valencia, M.; Pastor, M. A.; Fernández-Seara, M. A.; Artieda, J.; Martinerie, J.; Chavez, M.

    2009-06-01

    Modular structure is ubiquitous among real-world networks from related proteins to social groups. Here we analyze the modular organization of brain networks at a large scale (voxel level) extracted from functional magnetic resonance imaging signals. By using a random-walk-based method, we unveil the modularity of brain webs and show modules with a spatial distribution that matches anatomical structures with functional significance. The functional role of each node in the network is studied by analyzing its patterns of inter- and intramodular connections. Results suggest that the modular architecture constitutes the structural basis for the coexistence of functional integration of distant and specialized brain areas during normal brain activities at rest.

  10. Optimizing liquid effluent monitoring at a large nuclear complex.

    Science.gov (United States)

    Chou, Charissa J; Barnett, D Brent; Johnson, Vernon G; Olson, Phil M

    2003-12-01

    Effluent monitoring typically requires a large number of analytes and samples during the initial or startup phase of a facility. Once a baseline is established, the analyte list and sampling frequency may be reduced. Although there is a large body of literature relevant to the initial design, few, if any, published papers exist on updating established effluent monitoring programs. This paper statistically evaluates four years of baseline data to optimize the liquid effluent monitoring efficiency of a centralized waste treatment and disposal facility at a large defense nuclear complex. Specific objectives were to: (1) assess temporal variability in analyte concentrations, (2) determine operational factors contributing to waste stream variability, (3) assess the probability of exceeding permit limits, and (4) streamline the sampling and analysis regime. Results indicated that the probability of exceeding permit limits was one in a million under normal facility operating conditions, sampling frequency could be reduced, and several analytes could be eliminated. Furthermore, indicators such as gross alpha and gross beta measurements could be used in lieu of more expensive specific isotopic analyses (radium, cesium-137, and strontium-90) for routine monitoring. Study results were used by the state regulatory agency to modify monitoring requirements for a new discharge permit, resulting in an annual cost savings of US dollars 223,000. This case study demonstrates that statistical evaluation of effluent contaminant variability coupled with process knowledge can help plant managers and regulators streamline analyte lists and sampling frequencies based on detection history and environmental risk.

  11. Large-Eddy Simulations of Flows in Complex Terrain

    Science.gov (United States)

    Kosovic, B.; Lundquist, K. A.

    2011-12-01

    Large-eddy simulation as a methodology for numerical simulation of turbulent flows was first developed to study turbulent flows in atmospheric by Lilly (1967). The first LES were carried by Deardorff (1970) who used these simulations to study atmospheric boundary layers. Ever since, LES has been extensively used to study canonical atmospheric boundary layers, in most cases flat plate boundary layers under the assumption of horizontal homogeneity. Carefully designed LES of canonical convective and neutrally stratified and more recently stably stratified atmospheric boundary layers have contributed significantly to development of better understanding of these flows and their parameterizations in large scale models. These simulations were often carried out using codes specifically designed and developed for large-eddy simulations of horizontally homogeneous flows with periodic lateral boundary conditions. Recent developments in multi-scale numerical simulations of atmospheric flows enable numerical weather prediction (NWP) codes such as ARPS (Chow and Street, 2009), COAMPS (Golaz et al., 2009) and Weather Research and Forecasting model, to be used nearly seamlessly across a wide range of atmospheric scales from synoptic down to turbulent scales in atmospheric boundary layers. Before we can with confidence carry out multi-scale simulations of atmospheric flows, NWP codes must be validated for accurate performance in simulating flows over complex or inhomogeneous terrain. We therefore carry out validation of WRF-LES for simulations of flows over complex terrain using data from Askervein Hill (Taylor and Teunissen, 1985, 1987) and METCRAX (Whiteman et al., 2008) field experiments. WRF's nesting capability is employed with a one-way nested inner domain that includes complex terrain representation while the coarser outer nest is used to spin up fully developed atmospheric boundary layer turbulence and thus represent accurately inflow to the inner domain. LES of a

  12. Geophysical mapping of complex glaciogenic large-scale structures

    DEFF Research Database (Denmark)

    Høyer, Anne-Sophie

    2013-01-01

    This thesis presents the main results of a four year PhD study concerning the use of geophysical data in geological mapping. The study is related to the Geocenter project, “KOMPLEKS”, which focuses on the mapping of complex, large-scale geological structures. The study area is approximately 100 km2...... data types and co-interpret them in order to improve our geological understanding. However, in order to perform this successfully, methodological considerations are necessary. For instance, a structure indicated by a reflection in the seismic data is not always apparent in the resistivity data...... information) can be collected. The geophysical data are used together with geological analyses from boreholes and pits to interpret the geological history of the hill-island. The geophysical data reveal that the glaciotectonic structures truncate at the surface. The directions of the structures were mapped...

  13. Complex Formation Control of Large-Scale Intelligent Autonomous Vehicles

    Directory of Open Access Journals (Sweden)

    Ming Lei

    2012-01-01

    Full Text Available A new formation framework of large-scale intelligent autonomous vehicles is developed, which can realize complex formations while reducing data exchange. Using the proposed hierarchy formation method and the automatic dividing algorithm, vehicles are automatically divided into leaders and followers by exchanging information via wireless network at initial time. Then, leaders form formation geometric shape by global formation information and followers track their own virtual leaders to form line formation by local information. The formation control laws of leaders and followers are designed based on consensus algorithms. Moreover, collision-avoiding problems are considered and solved using artificial potential functions. Finally, a simulation example that consists of 25 vehicles shows the effectiveness of theory.

  14. Reorganizing Complex Network to Improve Large-Scale Multiagent Teamwork

    Directory of Open Access Journals (Sweden)

    Yang Xu

    2014-01-01

    Full Text Available Large-scale multiagent teamwork has been popular in various domains. Similar to human society infrastructure, agents only coordinate with some of the others, with a peer-to-peer complex network structure. Their organization has been proven as a key factor to influence their performance. To expedite team performance, we have analyzed that there are three key factors. First, complex network effects may be able to promote team performance. Second, coordination interactions coming from their sources are always trying to be routed to capable agents. Although they could be transferred across the network via different paths, their sources and sinks depend on the intrinsic nature of the team which is irrelevant to the network connections. In addition, the agents involved in the same plan often form a subteam and communicate with each other more frequently. Therefore, if the interactions between agents can be statistically recorded, we are able to set up an integrated network adjustment algorithm by combining the three key factors. Based on our abstracted teamwork simulations and the coordination statistics, we implemented the adaptive reorganization algorithm. The experimental results briefly support our design that the reorganized network is more capable of coordinating heterogeneous agents.

  15. Knowledge Sharing Strategies for Large Complex Building Projects.

    Directory of Open Access Journals (Sweden)

    Esra Bektas

    2013-06-01

    Full Text Available The construction industry is a project-based sector with a myriad of actors such as architects, construction companies, consultants, producers of building materials (Anumba et al., 2005. The interaction between the project partners is often quite limited, which leads to insufficient knowledge sharing during the project and knowledge being unavailable for reuse (Fruchter et al. 2002. The result can be a considerable amount of extra work, delays and cost overruns. Design outcomes that are supposed to function as boundary objects across different disciplines can lead to misinterpretation of requirements, project content and objectives. In this research, knowledge is seen as resulting from social interactions; knowledge resides in communities and it is generated through social relationships (Wenger 1998, Olsson et al. 2008. Knowledge is often tacit, intangible and context-dependent and it is articulated in the changing responsibilities, roles, attitudes and values that are present in the work environment (Bresnen et al., 2003. In a project environment, knowledge enables individuals to solve problems, take decisions, and apply these decisions to actions. In order to achieve a shared understanding and minimize the misunderstanding and misinterpretations among project actors, it is necessary to share knowledge (Fong 2003. Sharing knowledge is particularly crucial in large complex building projects (LCBPs in order to accelerate the building process, improve architectural quality and prevent mistakes or undesirable results. However, knowledge sharing is often hampered through professional or organizational boundaries or contractual concerns. When knowledge is seen as an organizational asset, there is little willingness among project organizations to share their knowledge. Individual people may recognize the need to promote knowledge sharing throughout the project, but typically there is no deliberate strategy agreed by all project partners to address

  16. Period doubling and chaos in large area Josephson junctions induced by rf signals

    DEFF Research Database (Denmark)

    Olsen, O. H.; Samuelsen, Mogens Rugholm

    1985-01-01

    The influence of an applied rf signal on the emitted radiation from a large area Josephson junction is examined. A model of the system is presented in the framework of the one-dimensional sine-Gordon equation. The model linearizes for small and large values of the amplitude of the applied signal...

  17. Large-scale seismic signal analysis with Hadoop

    Science.gov (United States)

    Addair, T. G.; Dodge, D. A.; Walter, W. R.; Ruppert, S. D.

    2014-05-01

    In seismology, waveform cross correlation has been used for years to produce high-precision hypocenter locations and for sensitive detectors. Because correlated seismograms generally are found only at small hypocenter separation distances, correlation detectors have historically been reserved for spotlight purposes. However, many regions have been found to produce large numbers of correlated seismograms, and there is growing interest in building next-generation pipelines that employ correlation as a core part of their operation. In an effort to better understand the distribution and behavior of correlated seismic events, we have cross correlated a global dataset consisting of over 300 million seismograms. This was done using a conventional distributed cluster, and required 42 days. In anticipation of processing much larger datasets, we have re-architected the system to run as a series of MapReduce jobs on a Hadoop cluster. In doing so we achieved a factor of 19 performance increase on a test dataset. We found that fundamental algorithmic transformations were required to achieve the maximum performance increase. Whereas in the original IO-bound implementation, we went to great lengths to minimize IO, in the Hadoop implementation where IO is cheap, we were able to greatly increase the parallelism of our algorithms by performing a tiered series of very fine-grained (highly parallelizable) transformations on the data. Each of these MapReduce jobs required reading and writing large amounts of data. But, because IO is very fast, and because the fine-grained computations could be handled extremely quickly by the mappers, the net was a large performance gain.

  18. Ethylene Regulates Levels of Ethylene Receptor/CTR1 Signaling Complexes in Arabidopsis thaliana*

    Science.gov (United States)

    Shakeel, Samina N.; Gao, Zhiyong; Amir, Madiha; Chen, Yi-Feng; Rai, Muneeza Iqbal; Haq, Noor Ul; Schaller, G. Eric

    2015-01-01

    The plant hormone ethylene is perceived by a five-member family of receptors in Arabidopsis thaliana. The receptors function in conjunction with the Raf-like kinase CTR1 to negatively regulate ethylene signal transduction. CTR1 interacts with multiple members of the receptor family based on co-purification analysis, interacting more strongly with receptors containing a receiver domain. Levels of membrane-associated CTR1 vary in response to ethylene, doing so in a post-transcriptional manner that correlates with ethylene-mediated changes in levels of the ethylene receptors ERS1, ERS2, EIN4, and ETR2. Interactions between CTR1 and the receptor ETR1 protect ETR1 from ethylene-induced turnover. Kinetic and dose-response analyses support a model in which two opposing factors control levels of the ethylene receptor/CTR1 complexes. Ethylene stimulates the production of new complexes largely through transcriptional induction of the receptors. However, ethylene also induces turnover of receptors, such that levels of ethylene receptor/CTR1 complexes decrease at higher ethylene concentrations. Implications of this model for ethylene signaling are discussed. PMID:25814663

  19. ALK signaling and target therapy in anaplastic large cell lymphoma

    Directory of Open Access Journals (Sweden)

    Fabrizio eTabbo

    2012-05-01

    Full Text Available The discovery by Morris SW et al. in 1994 of the genes contributing to the t(2;5(p23;q35 translocation has put the foundation for a molecular based recognition of Anaplastic Large Cell Lymphoma (ALCL and pointed out the need for a further stratification of T-cell neoplasia. Likewise the detection of ALK genetic lesions among many human cancers has defined unique subsets of cancer patients, providing new opportunities for innovative therapeutic interventions. The objective of this review is to appraise the molecular mechanisms driving ALK-mediated transformation, and to maintain the neoplastic phenotype. The understanding of these events will allow the design and implementation of novel tailored strategies for a well-defined subset of cancer patients.

  20. ALK Signaling and Target Therapy in Anaplastic Large Cell Lymphoma

    International Nuclear Information System (INIS)

    Tabbó, Fabrizio; Barreca, Antonella; Piva, Roberto; Inghirami, Giorgio

    2012-01-01

    The discovery by Morris et al. (1994) of the genes contributing to the t(2;5)(p23;q35) translocation has laid the foundation for a molecular based recognition of anaplastic large cell lymphoma and highlighted the need for a further stratification of T-cell neoplasia. Likewise the detection of anaplastic lymphoma kinase (ALK) genetic lesions among many human cancers has defined unique subsets of cancer patients, providing new opportunities for innovative therapeutic interventions. The objective of this review is to appraise the molecular mechanisms driving ALK-mediated transformation, and to maintain the neoplastic phenotype. The understanding of these events will allow the design and implementation of novel tailored strategies for a well-defined subset of cancer patients.

  1. A measurement system for large, complex software programs

    Science.gov (United States)

    Rone, Kyle Y.; Olson, Kitty M.; Davis, Nathan E.

    1994-01-01

    This paper describes measurement systems required to forecast, measure, and control activities for large, complex software development and support programs. Initial software cost and quality analysis provides the foundation for meaningful management decisions as a project evolves. In modeling the cost and quality of software systems, the relationship between the functionality, quality, cost, and schedule of the product must be considered. This explicit relationship is dictated by the criticality of the software being developed. This balance between cost and quality is a viable software engineering trade-off throughout the life cycle. Therefore, the ability to accurately estimate the cost and quality of software systems is essential to providing reliable software on time and within budget. Software cost models relate the product error rate to the percent of the project labor that is required for independent verification and validation. The criticality of the software determines which cost model is used to estimate the labor required to develop the software. Software quality models yield an expected error discovery rate based on the software size, criticality, software development environment, and the level of competence of the project and developers with respect to the processes being employed.

  2. NSP-CAS Protein Complexes: Emerging Signaling Modules in Cancer.

    Science.gov (United States)

    Wallez, Yann; Mace, Peter D; Pasquale, Elena B; Riedl, Stefan J

    2012-05-01

    The CAS (CRK-associated substrate) family of adaptor proteins comprises 4 members, which share a conserved modular domain structure that enables multiple protein-protein interactions, leading to the assembly of intracellular signaling platforms. Besides their physiological role in signal transduction downstream of a variety of cell surface receptors, CAS proteins are also critical for oncogenic transformation and cancer cell malignancy through associations with a variety of regulatory proteins and downstream effectors. Among the regulatory partners, the 3 recently identified adaptor proteins constituting the NSP (novel SH2-containing protein) family avidly bind to the conserved carboxy-terminal focal adhesion-targeting (FAT) domain of CAS proteins. NSP proteins use an anomalous nucleotide exchange factor domain that lacks catalytic activity to form NSP-CAS signaling modules. Additionally, the NSP SH2 domain can link NSP-CAS signaling assemblies to tyrosine-phosphorylated cell surface receptors. NSP proteins can potentiate CAS function by affecting key CAS attributes such as expression levels, phosphorylation state, and subcellular localization, leading to effects on cell adhesion, migration, and invasion as well as cell growth. The consequences of these activities are well exemplified by the role that members of both families play in promoting breast cancer cell invasiveness and resistance to antiestrogens. In this review, we discuss the intriguing interplay between the NSP and CAS families, with a particular focus on cancer signaling networks.

  3. Estimating large complex projects Estimando proyectos grandes y complejos

    Directory of Open Access Journals (Sweden)

    Cliff Schexnayder

    2007-08-01

    Full Text Available Managing large capital construction projects requires the coordination of a multitude of human, organizational, technical, and natural resources. Quite often, the engineering and construction complexities of such projects are overshadowed by economic, societal, and political challenges. The ramifications and effects, which result from differences between early project cost estimates and the bid price or the final project cost, are significant. Over the time span between the initiation of a project and the completion of construction many factors influence a project's final costs. This time span is normally several years in duration but for highly complex and technologically challenging projects, project duration can easily exceed a decade. Over that period, changes to the project scope often occur. The subject here is a presentation of strategies that support realistic cost estimating. Through literature review and interviews with transportation agencies in the U.S. and internationally the authors developed a database of the factors that are the root causes of cost estimation problemsGestionar proyectos de construcción de grandes capitales requiere de la coordinación de una multitud de recursos humanos, organizacionales, técnicos y naturales. Frecuentemente, las complejidades del diseño y construcción de esos grandes proyectos son tapadas por sus desafíos económicos, políticos y sociales. Las ramificaciones y efectos que resultan de las diferencias entre la estimación de costo inicial, el costo de la propuesta adjudicada y el costo final del proyecto son significativas. Hay numerosos factores que inciden en el costo final del proyecto entre su inicio y finalización. La duración es generalmente de varios años y puede incluso superar la década para aquellos especialmente complejos y desafiantes. En ese período de tiempo, cambios en los alcances del proyecto cambian frecuentemente. El tópico del presente artículo es mostrar

  4. Signal transduction by the major histocompatibility complex class I molecule

    DEFF Research Database (Denmark)

    Pedersen, A E; Skov, Svend; Bregenholt, S

    1999-01-01

    Ligation of cell surface major histocompatibility class I (MHC-I) proteins by antibodies, or by their native counter receptor, the CD8 molecule, mediates transduction of signals into the cells. MHC-I-mediated signaling can lead to both increased and decreased activity of the MHC-I-expressing cell...... and functioning, MHC-I molecules might be of importance for the maintenance of cellular homeostasis not only within the immune system, but also in the interplay between the immune system and other organ systems....

  5. A new large-scale manufacturing platform for complex biopharmaceuticals.

    Science.gov (United States)

    Vogel, Jens H; Nguyen, Huong; Giovannini, Roberto; Ignowski, Jolene; Garger, Steve; Salgotra, Anil; Tom, Jennifer

    2012-12-01

    Complex biopharmaceuticals, such as recombinant blood coagulation factors, are addressing critical medical needs and represent a growing multibillion-dollar market. For commercial manufacturing of such, sometimes inherently unstable, molecules it is important to minimize product residence time in non-ideal milieu in order to obtain acceptable yields and consistently high product quality. Continuous perfusion cell culture allows minimization of residence time in the bioreactor, but also brings unique challenges in product recovery, which requires innovative solutions. In order to maximize yield, process efficiency, facility and equipment utilization, we have developed, scaled-up and successfully implemented a new integrated manufacturing platform in commercial scale. This platform consists of a (semi-)continuous cell separation process based on a disposable flow path and integrated with the upstream perfusion operation, followed by membrane chromatography on large-scale adsorber capsules in rapid cycling mode. Implementation of the platform at commercial scale for a new product candidate led to a yield improvement of 40% compared to the conventional process technology, while product quality has been shown to be more consistently high. Over 1,000,000 L of cell culture harvest have been processed with 100% success rate to date, demonstrating the robustness of the new platform process in GMP manufacturing. While membrane chromatography is well established for polishing in flow-through mode, this is its first commercial-scale application for bind/elute chromatography in the biopharmaceutical industry and demonstrates its potential in particular for manufacturing of potent, low-dose biopharmaceuticals. Copyright © 2012 Wiley Periodicals, Inc.

  6. Microwave dynamic large signal waveform characterization of advanced InGaP HBT for power amplifiers

    Energy Technology Data Exchange (ETDEWEB)

    Zhao Lixin; Jin Zhi; Liu Xinyu, E-mail: zhaolixin@ime.ac.c [Institute of Microelectronics, Chinese Academy of Sciences, Beijing 100029 (China)

    2009-12-15

    In wireless mobile communications and wireless local area networks (WLAN), advanced InGaP HBT with power amplifiers are key components. In this paper, the microwave large signal dynamic waveform characteristics of an advanced InGaP HBT are investigated experimentally for 5.8 GHz power amplifier applications. The microwave large signal waveform distortions at various input power levels, especially at large signal level, are investigated and the reasons are analyzed. The output power saturation is also explained. These analyses will be useful for power amplifier designs. (semiconductor devices)

  7. Nonlinear signal processing for ultrasonic imaging of material complexity

    Czech Academy of Sciences Publication Activity Database

    Dos Santos, S.; Vejvodová, Šárka; Převorovský, Zdeněk

    2010-01-01

    Roč. 59, č. 2 (2010), s. 108-117 ISSN 1736-6046 Institutional research plan: CEZ:AV0Z20760514 Keywords : nonlinear signal processing * TR-NEWS * symmetry analysis * DORT Subject RIV: BI - Acoustics Impact factor: 0.464, year: 2010 www.eap.ee/proceedings

  8. Impacts of large dams on the complexity of suspended sediment dynamics in the Yangtze River

    Science.gov (United States)

    Wang, Yuankun; Rhoads, Bruce L.; Wang, Dong; Wu, Jichun; Zhang, Xiao

    2018-03-01

    The Yangtze River is one of the largest and most important rivers in the world. Over the past several decades, the natural sediment regime of the Yangtze River has been altered by the construction of dams. This paper uses multi-scale entropy analysis to ascertain the impacts of large dams on the complexity of high-frequency suspended sediment dynamics in the Yangtze River system, especially after impoundment of the Three Gorges Dam (TGD). In this study, the complexity of sediment dynamics is quantified by framing it within the context of entropy analysis of time series. Data on daily sediment loads for four stations located in the mainstem are analyzed for the past 60 years. The results indicate that dam construction has reduced the complexity of short-term (1-30 days) variation in sediment dynamics near the structures, but that complexity has actually increased farther downstream. This spatial pattern seems to reflect a filtering effect of the dams on the on the temporal pattern of sediment loads as well as decreased longitudinal connectivity of sediment transfer through the river system, resulting in downstream enhancement of the influence of local sediment inputs by tributaries on sediment dynamics. The TGD has had a substantial impact on the complexity of sediment series in the mainstem of the Yangtze River, especially after it became fully operational. This enhanced impact is attributed to the high trapping efficiency of this dam and its associated large reservoir. The sediment dynamics "signal" becomes more spatially variable after dam construction. This study demonstrates the spatial influence of dams on the high-frequency temporal complexity of sediment regimes and provides valuable information that can be used to guide environmental conservation of the Yangtze River.

  9. Design of General-purpose Industrial signal acquisition system in a large scientific device

    Science.gov (United States)

    Ren, Bin; Yang, Lei

    2018-02-01

    In order to measure the industrial signal of a large scientific device experiment, a set of industrial data general-purpose acquisition system has been designed. It can collect 4~20mA current signal and 0~10V voltage signal. Through the practical experiments, it shows that the system is flexible, reliable, convenient and economical, and the system has characters of high definition and strong anti-interference ability. Thus, the system fully meets the design requirements..

  10. The Fyn tyrosine kinase binds Irs-1 and forms a distinct signaling complex during insulin stimulation.

    Science.gov (United States)

    Sun, X J; Pons, S; Asano, T; Myers, M G; Glasheen, E; White, M F

    1996-05-03

    Irs-proteins link the receptors for insulin/IGF-1, growth hormones, and several interleukins and interferons to signaling proteins that contain Src homology-2 (SH2). To identify new Irs-1-binding proteins, we screened a mouse embryo expression library with recombinant [32P]Irs-1, which revealed a specific association between p59fyn and Irs-1. The SH2 domain in p59fyn bound to phosphorylated Tyr895 and Tyr1172, which are located in YXX(L/I) motifs. Mutation of p59fyn at the COOH-terminal tyrosine phosphorylation site (Tyr531) enhanced its binding to Irs-1 during insulin stimulation. Binding experiments with various SH2 protein revealed that Grb-2 was largely excluded from Irs-1 complexes containing p59fyn, whereas Grb-2 and p85 occurred in the same Irs-1 complex. By comparison with the insulin receptor, p59fyn kinase phosphorylated a unique cohort of tyrosine residues in Irs-1. These results outline a role for p59fyn or other related Src-kinases during insulin and cytokine signaling.

  11. Small- and large-signal modeling of InP HBTs in transferred-substrate technology

    DEFF Research Database (Denmark)

    Johansen, Tom Keinicke; Rudolph, Matthias; Jensen, Thomas

    2014-01-01

    In this paper, the small- and large-signal modeling of InP heterojunction bipolar transistors (HBTs) in transferred substrate (TS) technology is investigated. The small-signal equivalent circuit parameters for TS-HBTs in two-terminal and three-terminal configurations are determined by employing...

  12. Large-Signal Code TESLA: Improvements in the Implementation and in the Model

    National Research Council Canada - National Science Library

    Chernyavskiy, Igor A; Vlasov, Alexander N; Anderson, Jr., Thomas M; Cooke, Simon J; Levush, Baruch; Nguyen, Khanh T

    2006-01-01

    We describe the latest improvements made in the large-signal code TESLA, which include transformation of the code to a Fortran-90/95 version with dynamical memory allocation and extension of the model...

  13. Regulation of Drosophila Brain Wiring by Neuropil Interactions via a Slit-Robo-RPTP Signaling Complex.

    Science.gov (United States)

    Oliva, Carlos; Soldano, Alessia; Mora, Natalia; De Geest, Natalie; Claeys, Annelies; Erfurth, Maria-Luise; Sierralta, Jimena; Ramaekers, Ariane; Dascenco, Dan; Ejsmont, Radoslaw K; Schmucker, Dietmar; Sanchez-Soriano, Natalia; Hassan, Bassem A

    2016-10-24

    The axonal wiring molecule Slit and its Round-About (Robo) receptors are conserved regulators of nerve cord patterning. Robo receptors also contribute to wiring brain circuits. Whether molecular mechanisms regulating these signals are modified to fit more complex brain wiring processes is unclear. We investigated the role of Slit and Robo receptors in wiring Drosophila higher-order brain circuits and identified differences in the cellular and molecular mechanisms of Robo/Slit function. First, we find that signaling by Robo receptors in the brain is regulated by the Receptor Protein Tyrosine Phosphatase RPTP69d. RPTP69d increases membrane availability of Robo3 without affecting its phosphorylation state. Second, we detect no midline localization of Slit during brain development. Instead, Slit is enriched in the mushroom body, a neuronal structure covering large areas of the brain. Thus, a divergent molecular mechanism regulates neuronal circuit wiring in the Drosophila brain, partly in response to signals from the mushroom body. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. RESEARCH ON COMPLEX, LARGE INDUSTRIAL PROJECTS IN TRANSNATIONAL ENVIRONMENT

    Directory of Open Access Journals (Sweden)

    Florin POPESCU

    2016-12-01

    Full Text Available More and more projects from different industrial sectors developed in transnational environment are becoming more characterized as "complex". In recent years, there has been much discussion and controversy about the complexity of the projects, and, despite what has been written and said in various papers, journals and professional conferences, more confusion than clarification was created, complexity of projects being interpreted differently from one author to another. Most of the literature studied is based on linear, analytical and rational approach, focusing on the size of project management planning and control and actually less on projects that are characterized as taking place and grow into a dynamic socio-human environment in a continuous change. This study represents a critical review of existing theoretical models found in literature, highlighting their limitations. The output of this literature study represents an integration of different approaches concerning complexity under one umbrella to provide a common understanding of the evolution of this concept.

  15. Improved Peak Detection and Deconvolution of Native Electrospray Mass Spectra from Large Protein Complexes.

    Science.gov (United States)

    Lu, Jonathan; Trnka, Michael J; Roh, Soung-Hun; Robinson, Philip J J; Shiau, Carrie; Fujimori, Danica Galonic; Chiu, Wah; Burlingame, Alma L; Guan, Shenheng

    2015-12-01

    Native electrospray-ionization mass spectrometry (native MS) measures biomolecules under conditions that preserve most aspects of protein tertiary and quaternary structure, enabling direct characterization of large intact protein assemblies. However, native spectra derived from these assemblies are often partially obscured by low signal-to-noise as well as broad peak shapes because of residual solvation and adduction after the electrospray process. The wide peak widths together with the fact that sequential charge state series from highly charged ions are closely spaced means that native spectra containing multiple species often suffer from high degrees of peak overlap or else contain highly interleaved charge envelopes. This situation presents a challenge for peak detection, correct charge state and charge envelope assignment, and ultimately extraction of the relevant underlying mass values of the noncovalent assemblages being investigated. In this report, we describe a comprehensive algorithm developed for addressing peak detection, peak overlap, and charge state assignment in native mass spectra, called PeakSeeker. Overlapped peaks are detected by examination of the second derivative of the raw mass spectrum. Charge state distributions of the molecular species are determined by fitting linear combinations of charge envelopes to the overall experimental mass spectrum. This software is capable of deconvoluting heterogeneous, complex, and noisy native mass spectra of large protein assemblies as demonstrated by analysis of (1) synthetic mononucleosomes containing severely overlapping peaks, (2) an RNA polymerase II/α-amanitin complex with many closely interleaved ion signals, and (3) human TriC complex containing high levels of background noise. Graphical Abstract ᅟ.

  16. DNA-Directed Assembly of Capture Tools for Constitutional Studies of Large Protein Complexes.

    Science.gov (United States)

    Meyer, Rebecca; Faesen, Alex; Vogel, Katrin; Jeganathan, Sadasivam; Musacchio, Andrea; Niemeyer, Christof M

    2015-06-10

    Large supramolecular protein complexes, such as the molecular machinery involved in gene regulation, cell signaling, or cell division, are key in all fundamental processes of life. Detailed elucidation of structure and dynamics of such complexes can be achieved by reverse-engineering parts of the complexes in order to probe their interactions with distinctive binding partners in vitro. The exploitation of DNA nanostructures to mimic partially assembled supramolecular protein complexes in which the presence and state of two or more proteins are decisive for binding of additional building blocks is reported here. To this end, four-way DNA Holliday junction motifs bearing a fluorescein and a biotin tag, for tracking and affinity capture, respectively, are site-specifically functionalized with centromeric protein (CENP) C and CENP-T. The latter serves as baits for binding of the so-called KMN component, thereby mimicking early stages of the assembly of kinetochores, structures that mediate and control the attachment of microtubules to chromosomes in the spindle apparatus. Results from pull-down experiments are consistent with the hypothesis that CENP-C and CENP-T may bind cooperatively to the KMN network. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Machines vs. ensembles: effective MAPK signaling through heterogeneous sets of protein complexes.

    Directory of Open Access Journals (Sweden)

    Ryan Suderman

    Full Text Available Despite the importance of intracellular signaling networks, there is currently no consensus regarding the fundamental nature of the protein complexes such networks employ. One prominent view involves stable signaling machines with well-defined quaternary structures. The combinatorial complexity of signaling networks has led to an opposing perspective, namely that signaling proceeds via heterogeneous pleiomorphic ensembles of transient complexes. Since many hypotheses regarding network function rely on how we conceptualize signaling complexes, resolving this issue is a central problem in systems biology. Unfortunately, direct experimental characterization of these complexes has proven technologically difficult, while combinatorial complexity has prevented traditional modeling methods from approaching this question. Here we employ rule-based modeling, a technique that overcomes these limitations, to construct a model of the yeast pheromone signaling network. We found that this model exhibits significant ensemble character while generating reliable responses that match experimental observations. To contrast the ensemble behavior, we constructed a model that employs hierarchical assembly pathways to produce scaffold-based signaling machines. We found that this machine model could not replicate the experimentally observed combinatorial inhibition that arises when the scaffold is overexpressed. This finding provides evidence against the hierarchical assembly of machines in the pheromone signaling network and suggests that machines and ensembles may serve distinct purposes in vivo. In some cases, e.g. core enzymatic activities like protein synthesis and degradation, machines assembled via hierarchical energy landscapes may provide functional stability for the cell. In other cases, such as signaling, ensembles may represent a form of weak linkage, facilitating variation and plasticity in network evolution. The capacity of ensembles to signal effectively

  18. Data mining in large sets of complex data

    CERN Document Server

    Cordeiro, Robson L F; Júnior, Caetano Traina

    2013-01-01

    The amount and the complexity of the data gathered by current enterprises are increasing at an exponential rate. Consequently, the analysis of Big Data is nowadays a central challenge in Computer Science, especially for complex data. For example, given a satellite image database containing tens of Terabytes, how can we find regions aiming at identifying native rainforests, deforestation or reforestation? Can it be made automatically? Based on the work discussed in this book, the answers to both questions are a sound "yes", and the results can be obtained in just minutes. In fact, results that

  19. Large-signal analysis of DC motor drive system using state-space averaging technique

    International Nuclear Information System (INIS)

    Bekir Yildiz, Ali

    2008-01-01

    The analysis of a separately excited DC motor driven by DC-DC converter is realized by using state-space averaging technique. Firstly, a general and unified large-signal averaged circuit model for DC-DC converters is given. The method converts power electronic systems, which are periodic time-variant because of their switching operation, to unified and time independent systems. Using the averaged circuit model enables us to combine the different topologies of converters. Thus, all analysis and design processes about DC motor can be easily realized by using the unified averaged model which is valid during whole period. Some large-signal variations such as speed and current relating to DC motor, steady-state analysis, large-signal and small-signal transfer functions are easily obtained by using the averaged circuit model

  20. Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed

    Science.gov (United States)

    Hsu, Li-Jin; Hong, Qunying; Chen, Shur-Tzu; Kuo, Hsiang-Lin; Schultz, Lori; Heath, John; Lin, Sing-Ru; Lee, Ming-Hui; Li, Dong-Zhang; Li, Zih-Ling; Cheng, Hui-Ching; Armand, Gerard; Chang, Nan-Shan

    2017-01-01

    Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed. PMID:27845895

  1. Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.

    Science.gov (United States)

    Hsu, Li-Jin; Hong, Qunying; Chen, Shur-Tzu; Kuo, Hsiang-Lin; Schultz, Lori; Heath, John; Lin, Sing-Ru; Lee, Ming-Hui; Li, Dong-Zhang; Li, Zih-Ling; Cheng, Hui-Ching; Armand, Gerard; Chang, Nan-Shan

    2017-03-21

    Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.

  2. ABOUT MODELING COMPLEX ASSEMBLIES IN SOLIDWORKS – LARGE AXIAL BEARING

    Directory of Open Access Journals (Sweden)

    Cătălin IANCU

    2017-12-01

    Full Text Available In this paperwork is presented the modeling strategy used in SOLIDWORKS for modeling special items as large axial bearing and the steps to be taken in order to obtain a better design. In the paper are presented the features that are used for modeling parts, and then the steps that must be taken in order to obtain the 3D model of a large axial bearing used for bucket-wheel equipment for charcoal moving.

  3. SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes

    Directory of Open Access Journals (Sweden)

    Sebastian Kupka

    2016-08-01

    Full Text Available Recruitment of the deubiquitinase CYLD to signaling complexes is mediated by its interaction with HOIP, the catalytically active component of the linear ubiquitin chain assembly complex (LUBAC. Here, we identify SPATA2 as a constitutive direct binding partner of HOIP that bridges the interaction between CYLD and HOIP. SPATA2 recruitment to TNFR1- and NOD2-signaling complexes is dependent on HOIP, and loss of SPATA2 abolishes CYLD recruitment. Deficiency in SPATA2 exerts limited effects on gene activation pathways but diminishes necroptosis induced by tumor necrosis factor (TNF, resembling loss of CYLD. In summary, we describe SPATA2 as a previously unrecognized factor in LUBAC-dependent signaling pathways that serves as an adaptor between HOIP and CYLD, thereby enabling recruitment of CYLD to signaling complexes.

  4. Improved Empirical Mode Decomposition Algorithm of Processing Complex Signal for IoT Application

    OpenAIRE

    Yang, Xianzhao; Cheng, Gengguo; Liu, Huikang

    2015-01-01

    Hilbert-Huang transform is widely used in signal analysis. However, due to its inadequacy in estimating both the maximum and the minimum values of the signals at both ends of the border, traditional HHT is easy to produce boundary error in empirical mode decomposition (EMD) process. To overcome this deficiency, this paper proposes an enhanced empirical mode decomposition algorithm for processing complex signal. Our work mainly focuses on two aspects. On one hand, we develop a technique to obt...

  5. Unraveling the Complexities of Androgen Receptor Signaling in Prostate Cancer Cells

    OpenAIRE

    Heemers, Hannelore V.; Tindall, Donald J.

    2009-01-01

    Androgen signaling is critical for proliferation of prostate cancer cells but cannot be fully inhibited by current androgen deprivation therapies. A study by Xu et al. in this issue of Cancer Cell provides insights into the complexities of androgen signaling in prostate cancer and suggests avenues to target a subset of androgen-sensitive genes.

  6. Normalization of informatisation parameter on airfield light-signal bar at flights in complex meteorological conditions

    Directory of Open Access Journals (Sweden)

    П.В. Попов

    2005-03-01

    Full Text Available  The technique of maintenance of the set level of flights safetivness is developed by normalization of informatisation parameters functional groups of light-signal lightings at technological stages of interaction of crew of the airplane with the airfield light-signals bar at flights in a complex weathercast conditions.

  7. Requirement of the Mre11 complex and exonuclease 1 for activation of the Mec1 signaling pathway.

    Science.gov (United States)

    Nakada, Daisuke; Hirano, Yukinori; Sugimoto, Katsunori

    2004-11-01

    The large protein kinases, ataxia-telangiectasia mutated (ATM) and ATM-Rad3-related (ATR), orchestrate DNA damage checkpoint pathways. In budding yeast, ATM and ATR homologs are encoded by TEL1 and MEC1, respectively. The Mre11 complex consists of two highly related proteins, Mre11 and Rad50, and a third protein, Xrs2 in budding yeast or Nbs1 in mammals. The Mre11 complex controls the ATM/Tel1 signaling pathway in response to double-strand break (DSB) induction. We show here that the Mre11 complex functions together with exonuclease 1 (Exo1) in activation of the Mec1 signaling pathway after DNA damage and replication block. Mec1 controls the checkpoint responses following UV irradiation as well as DSB induction. Correspondingly, the Mre11 complex and Exo1 play an overlapping role in activation of DSB- and UV-induced checkpoints. The Mre11 complex and Exo1 collaborate in producing long single-stranded DNA (ssDNA) tails at DSB ends and promote Mec1 association with the DSBs. The Ddc1-Mec3-Rad17 complex associates with sites of DNA damage and modulates the Mec1 signaling pathway. However, Ddc1 association with DSBs does not require the function of the Mre11 complex and Exo1. Mec1 controls checkpoint responses to stalled DNA replication as well. Accordingly, the Mre11 complex and Exo1 contribute to activation of the replication checkpoint pathway. Our results provide a model in which the Mre11 complex and Exo1 cooperate in generating long ssDNA tracts and thereby facilitate Mec1 association with sites of DNA damage or replication block.

  8. Complex Signal Kurtosis and Independent Component Analysis for Wideband Radio Frequency Interference Detection

    Science.gov (United States)

    Schoenwald, Adam; Mohammed, Priscilla; Bradley, Damon; Piepmeier, Jeffrey; Wong, Englin; Gholian, Armen

    2016-01-01

    Radio-frequency interference (RFI) has negatively implicated scientific measurements across a wide variation passive remote sensing satellites. This has been observed in the L-band radiometers SMOS, Aquarius and more recently, SMAP [1, 2]. RFI has also been observed at higher frequencies such as K band [3]. Improvements in technology have allowed wider bandwidth digital back ends for passive microwave radiometry. A complex signal kurtosis radio frequency interference detector was developed to help identify corrupted measurements [4]. This work explores the use of ICA (Independent Component Analysis) as a blind source separation technique to pre-process radiometric signals for use with the previously developed real and complex signal kurtosis detectors.

  9. The effect of hypobaric hypoxia on multichannel EEG signal complexity.

    Science.gov (United States)

    Papadelis, Christos; Kourtidou-Papadeli, Chrysoula; Bamidis, Panagiotis D; Maglaveras, Nikos; Pappas, Konstantinos

    2007-01-01

    The objective of this study was the development and evaluation of nonlinear electroencephalography parameters which assess hypoxia-induced EEG alterations, and describe the temporal characteristics of different hypoxic levels' residual effect upon the brain electrical activity. Multichannel EEG, pO2, pCO2, ECG, and respiration measurements were recorded from 10 subjects exposed to three experimental conditions (100% oxygen, hypoxia, recovery) at three-levels of reduced barometric pressure. The mean spectral power of EEG under each session and altitude were estimated for the standard bands. Approximate Entropy (ApEn) of EEG segments was calculated, and the ApEn's time-courses were smoothed by a moving average filter. On the smoothed diagrams, parameters were defined. A significant increase in total power and power of theta and alpha bands was observed during hypoxia. Visual interpretation of ApEn time-courses revealed a characteristic pattern (decreasing during hypoxia and recovering after oxygen re-administration). The introduced qEEG parameters S1 and K1 distinguished successfully the three hypoxic conditions. The introduced parameters based on ApEn time-courses are assessing reliably and effectively the different hypoxic levels. ApEn decrease may be explained by neurons' functional isolation due to hypoxia since decreased complexity corresponds to greater autonomy of components, although this interpretation should be further supported by electrocorticographic animal studies. The introduced qEEG parameters seem to be appropriate for assessing the hypoxia-related neurophysiological state of patients in the hyperbaric chambers in the treatment of decompression sickness, carbon dioxide poisoning, and mountaineering.

  10. Use of multiple singular value decompositions to analyze complex intracellular calcium ion signals

    KAUST Repository

    Martinez, Josue G.; Huang, Jianhua Z.; Burghardt, Robert C.; Barhoumi, Rola; Carroll, Raymond J.

    2009-01-01

    ) to extract the signals from such movies, in a way that is semi-automatic and tuned closely to the actual data and their many complexities. These complexities include the following. First, the images themselves are of no interest: all interest focuses

  11. A new traffic control design method for large networks with signalized intersections

    Science.gov (United States)

    Leininger, G. G.; Colony, D. C.; Seldner, K.

    1979-01-01

    The paper presents a traffic control design technique for application to large traffic networks with signalized intersections. It is shown that the design method adopts a macroscopic viewpoint to establish a new traffic modelling procedure in which vehicle platoons are subdivided into main stream queues and turning queues. Optimization of the signal splits minimizes queue lengths in the steady state condition and improves traffic flow conditions, from the viewpoint of the traveling public. Finally, an application of the design method to a traffic network with thirty-three signalized intersections is used to demonstrate the effectiveness of the proposed technique.

  12. Large-eddy simulation of atmospheric flow over complex terrain

    Energy Technology Data Exchange (ETDEWEB)

    Bechmann, A.

    2006-11-15

    The present report describes the development and validation of a turbulence model designed for atmospheric flows based on the concept of Large-Eddy Simulation (LES). The background for the work is the high Reynolds number k - epsilon model, which has been implemented on a finite-volume code of the incompressible Reynolds-averaged Navier-Stokes equations (RANS). The k - epsilon model is traditionally used for RANS computations, but is here developed to also enable LES. LES is able to provide detailed descriptions of a wide range of engineering flows at low Reynolds numbers. For atmospheric flows, however, the high Reynolds numbers and the rough surface of the earth provide difficulties normally not compatible with LES. Since these issues are most severe near the surface they are addressed by handling the near surface region with RANS and only use LES above this region. Using this method, the developed turbulence model is able to handle both engineering and atmospheric flows and can be run in both RANS or LES mode. For LES simulations a time-dependent wind field that accurately represents the turbulent structures of a wind environment must be prescribed at the computational inlet. A method is implemented where the turbulent wind field from a separate LES simulation can be used as inflow. To avoid numerical dissipation of turbulence special care is paid to the numerical method, e.g. the turbulence model is calibrated with the specific numerical scheme used. This is done by simulating decaying isotropic and homogeneous turbulence. Three atmospheric test cases are investigated in order to validate the behavior of the presented turbulence model. Simulation of the neutral atmospheric boundary layer, illustrates the turbulence model ability to generate and maintain the turbulent structures responsible for boundary layer transport processes. Velocity and turbulence profiles are in good agreement with measurements. Simulation of the flow over the Askervein hill is also

  13. A simple iterative independent component analysis algorithm for vibration source signal identification of complex structures

    Directory of Open Access Journals (Sweden)

    Dong-Sup Lee

    2015-01-01

    Full Text Available Independent Component Analysis (ICA, one of the blind source separation methods, can be applied for extracting unknown source signals only from received signals. This is accomplished by finding statistical independence of signal mixtures and has been successfully applied to myriad fields such as medical science, image processing, and numerous others. Nevertheless, there are inherent problems that have been reported when using this technique: insta- bility and invalid ordering of separated signals, particularly when using a conventional ICA technique in vibratory source signal identification of complex structures. In this study, a simple iterative algorithm of the conventional ICA has been proposed to mitigate these problems. The proposed method to extract more stable source signals having valid order includes an iterative and reordering process of extracted mixing matrix to reconstruct finally converged source signals, referring to the magnitudes of correlation coefficients between the intermediately separated signals and the signals measured on or nearby sources. In order to review the problems of the conventional ICA technique and to vali- date the proposed method, numerical analyses have been carried out for a virtual response model and a 30 m class submarine model. Moreover, in order to investigate applicability of the proposed method to real problem of complex structure, an experiment has been carried out for a scaled submarine mockup. The results show that the proposed method could resolve the inherent problems of a conventional ICA technique.

  14. Large-eddy simulation of atmospheric flow over complex terrain

    DEFF Research Database (Denmark)

    Bechmann, Andreas

    2007-01-01

    The present report describes the development and validation of a turbulence model designed for atmospheric flows based on the concept of Large-Eddy Simulation (LES). The background for the work is the high Reynolds number k - #epsilon# model, which has been implemented on a finite-volume code...... turbulence model is able to handle both engineering and atmospheric flows and can be run in both RANS or LES mode. For LES simulations a time-dependent wind field that accurately represents the turbulent structures of a wind environment must be prescribed at the computational inlet. A method is implemented...... where the turbulent wind field from a separate LES simulation can be used as inflow. To avoid numerical dissipation of turbulence special care is paid to the numerical method, e.g. the turbulence model is calibrated with the specific numerical scheme used. This is done by simulating decaying isotropic...

  15. Optimizing Liquid Effluent Monitoring at a Large Nuclear Complex

    International Nuclear Information System (INIS)

    Chou, Charissa J.; Johnson, V.G.; Barnett, Brent B.; Olson, Phillip M.

    2003-01-01

    Monitoring data for a centralized effluent treatment and disposal facility at the Hanford Site, a defense nuclear complex undergoing cleanup and decommissioning in southeast Washington State, was evaluated to optimize liquid effluent monitoring efficiency. Wastewater from several facilities is collected and discharged to the ground at a common disposal site. The discharged water infiltrates through 60 m of soil column to the groundwater, which eventually flows into the Columbia River, the second largest river in the contiguous United States. Protection of this important natural resource is the major objective of both cleanup and groundwater and effluent monitoring activities at the Hanford Site. Four years of effluent data were evaluated for this study. More frequent sampling was conducted during the first year of operation to assess temporal variability in analyte concentrations, to determine operational factors contributing to waste stream variability and to assess the probability of exceeding permit limits. Subsequently, the study was updated which included evaluation of the sampling and analysis regime. It was concluded that the probability of exceeding permit limits was one in a million under normal operating conditions, sampling frequency could be reduced, and several analytes could be eliminated, while indicators could be substituted for more expensive analyses. Findings were used by the state regulatory agency to modify monitoring requirements for a new discharge permit. The primary focus of this paper is on the statistical approaches and rationale that led to the successful permit modification and to a more cost-effective effluent monitoring program

  16. Aiding the Detection of QRS Complex in ECG Signals by Detecting S Peaks Independently.

    Science.gov (United States)

    Sabherwal, Pooja; Singh, Latika; Agrawal, Monika

    2018-03-30

    In this paper, a novel algorithm for the accurate detection of QRS complex by combining the independent detection of R and S peaks, using fusion algorithm is proposed. R peak detection has been extensively studied and is being used to detect the QRS complex. Whereas, S peaks, which is also part of QRS complex can be independently detected to aid the detection of QRS complex. In this paper, we suggest a method to first estimate S peak from raw ECG signal and then use them to aid the detection of QRS complex. The amplitude of S peak in ECG signal is relatively weak than corresponding R peak, which is traditionally used for the detection of QRS complex, therefore, an appropriate digital filter is designed to enhance the S peaks. These enhanced S peaks are then detected by adaptive thresholding. The algorithm is validated on all the signals of MIT-BIH arrhythmia database and noise stress database taken from physionet.org. The algorithm performs reasonably well even for the signals highly corrupted by noise. The algorithm performance is confirmed by sensitivity and positive predictivity of 99.99% and the detection accuracy of 99.98% for QRS complex detection. The number of false positives and false negatives resulted while analysis has been drastically reduced to 80 and 42 against the 98 and 84 the best results reported so far.

  17. Application of complex discrete wavelet transform in classification of Doppler signals using complex-valued artificial neural network.

    Science.gov (United States)

    Ceylan, Murat; Ceylan, Rahime; Ozbay, Yüksel; Kara, Sadik

    2008-09-01

    In biomedical signal classification, due to the huge amount of data, to compress the biomedical waveform data is vital. This paper presents two different structures formed using feature extraction algorithms to decrease size of feature set in training and test data. The proposed structures, named as wavelet transform-complex-valued artificial neural network (WT-CVANN) and complex wavelet transform-complex-valued artificial neural network (CWT-CVANN), use real and complex discrete wavelet transform for feature extraction. The aim of using wavelet transform is to compress data and to reduce training time of network without decreasing accuracy rate. In this study, the presented structures were applied to the problem of classification in carotid arterial Doppler ultrasound signals. Carotid arterial Doppler ultrasound signals were acquired from left carotid arteries of 38 patients and 40 healthy volunteers. The patient group included 22 males and 16 females with an established diagnosis of the early phase of atherosclerosis through coronary or aortofemoropopliteal (lower extremity) angiographies (mean age, 59 years; range, 48-72 years). Healthy volunteers were young non-smokers who seem to not bear any risk of atherosclerosis, including 28 males and 12 females (mean age, 23 years; range, 19-27 years). Sensitivity, specificity and average detection rate were calculated for comparison, after training and test phases of all structures finished. These parameters have demonstrated that training times of CVANN and real-valued artificial neural network (RVANN) were reduced using feature extraction algorithms without decreasing accuracy rate in accordance to our aim.

  18. Hydrogen Exchange Differences between Chemoreceptor Signaling Complexes Localize to Functionally Important Subdomains

    Science.gov (United States)

    2015-01-01

    The goal of understanding mechanisms of transmembrane signaling, one of many key life processes mediated by membrane proteins, has motivated numerous studies of bacterial chemotaxis receptors. Ligand binding to the receptor causes a piston motion of an α helix in the periplasmic and transmembrane domains, but it is unclear how the signal is then propagated through the cytoplasmic domain to control the activity of the associated kinase CheA. Recent proposals suggest that signaling in the cytoplasmic domain involves opposing changes in dynamics in different subdomains. However, it has been difficult to measure dynamics within the functional system, consisting of extended arrays of receptor complexes with two other proteins, CheA and CheW. We have combined hydrogen exchange mass spectrometry with vesicle template assembly of functional complexes of the receptor cytoplasmic domain to reveal that there are significant signaling-associated changes in exchange, and these changes localize to key regions of the receptor involved in the excitation and adaptation responses. The methylation subdomain exhibits complex changes that include slower hydrogen exchange in complexes in a kinase-activating state, which may be partially consistent with proposals that this subdomain is stabilized in this state. The signaling subdomain exhibits significant protection from hydrogen exchange in complexes in a kinase-activating state, suggesting a tighter and/or larger interaction interface with CheA and CheW in this state. These first measurements of the stability of protein subdomains within functional signaling complexes demonstrate the promise of this approach for measuring functionally important protein dynamics within the various physiologically relevant states of multiprotein complexes. PMID:25420045

  19. Simulation study on effects of signaling network structure on the developmental increase in complexity

    Energy Technology Data Exchange (ETDEWEB)

    Keranen, Soile V.E.

    2003-04-02

    The developmental increase in structural complexity in multicellular life forms depends on local, often non-periodic differences in gene expression. These depend on a network of gene-gene interactions coded within the organismal genome. To better understand how genomic information generates complex expression patterns, I have modeled the pattern forming behavior of small artificial genomes in virtual blastoderm embryos. I varied several basic properties of these genomic signaling networks, such as the number of genes, the distributions of positive (inductive) and negative (repressive) interactions, and the strengths of gene-gene interactions, and analyzed their effects on developmental pattern formation. The results show how even simple genomes can generate complex non-periodic patterns under suitable conditions. They also show how the frequency of complex patterns depended on the numbers and relative arrangements of positive and negative interactions. For example, negative co-regulation of signaling pathway components increased the likelihood of (complex) patterns relative to differential negative regulation of the pathway components. Interestingly, neither quantitative differences either in strengths of signaling interactions nor multiple response thresholds to signal concentration (as in morphogen gradients) were essential for formation of multiple, spatially unique cell types. Thus, with combinatorial code of gene regulation and hierarchical signaling interactions, it is theoretically possible to organize metazoan embryogenesis with just a small fraction of the metazoan genome. Because even small networks can generate complex patterns when they contain a suitable set of connections, evolution of metazoan complexity may have depended more on selection for favourable configurations of signaling interactions than on the increase in numbers of regulatory genes.

  20. Simultaneous electrical and mechanical resonance drive for large signal amplification of micro resonators

    KAUST Repository

    Hasan, M. H.

    2018-01-12

    Achieving large signal-noise ratio using low levels of excitation signal is key requirement for practical applications of micro and nano electromechanical resonators. In this work, we introduce the double electromechanical resonance drive concept to achieve an order-of-magnitude dynamic signal amplification in micro resonators. The concept relies on simultaneously activating the micro-resonator mechanical and electrical resonance frequencies. We report an input voltage amplification up to 15 times for a micro-resonator when its electrical resonance is tuned to match the mechanical resonance that leads to dynamic signal amplification in air (Quality factor enhancement). Furthermore, using a multi-frequency excitation technique, input voltage and vibrational amplification of up to 30 times were shown for the same micro-resonator while relaxing the need to match its mechanical and electrical resonances.

  1. Simultaneous electrical and mechanical resonance drive for large signal amplification of micro resonators

    KAUST Repository

    Hasan, M. H.; Alsaleem, F. M.; Jaber, Nizar; Hafiz, Md Abdullah Al; Younis, Mohammad I.

    2018-01-01

    Achieving large signal-noise ratio using low levels of excitation signal is key requirement for practical applications of micro and nano electromechanical resonators. In this work, we introduce the double electromechanical resonance drive concept to achieve an order-of-magnitude dynamic signal amplification in micro resonators. The concept relies on simultaneously activating the micro-resonator mechanical and electrical resonance frequencies. We report an input voltage amplification up to 15 times for a micro-resonator when its electrical resonance is tuned to match the mechanical resonance that leads to dynamic signal amplification in air (Quality factor enhancement). Furthermore, using a multi-frequency excitation technique, input voltage and vibrational amplification of up to 30 times were shown for the same micro-resonator while relaxing the need to match its mechanical and electrical resonances.

  2. Received signal strength in large-scale wireless relay sensor network: a stochastic ray approach

    NARCIS (Netherlands)

    Hu, L.; Chen, Y.; Scanlon, W.G.

    2011-01-01

    The authors consider a point percolation lattice representation of a large-scale wireless relay sensor network (WRSN) deployed in a cluttered environment. Each relay sensor corresponds to a grid point in the random lattice and the signal sent by the source is modelled as an ensemble of photons that

  3. Measurement of the Low Frequency Noise of MOSFETs under Large Signal RF Excitation

    NARCIS (Netherlands)

    van der Wel, A.P.; Klumperink, Eric A.M.; Nauta, Bram

    2002-01-01

    A measurement technique [1] is presented that allows measurement of MOSFET low frequency (LF) noise under large signal RF (Radio Frequency) excitation. Measurements indicate that MOSFETS exhibit a reduction in LF noise when they are cycled from inversion to accummulation and that this reduction does

  4. Large-signal characterization of DDR silicon IMPATTs operating in millimeter-wave and terahertz regime

    International Nuclear Information System (INIS)

    Acharyya, Aritra; Banerjee, J. P.; Chakraborty, Jit; Das, Kausik; Datta, Subir; De, Pritam; Banerjee, Suranjana

    2013-01-01

    The authors have carried out the large-signal characterization of silicon-based double-drift region (DDR) impact avalanche transit time (IMPATT) devices designed to operate up to 0.5 THz using a large-signal simulation method developed by the authors based on non-sinusoidal voltage excitation. The effect of band-to-band tunneling as well as parasitic series resistance on the large-signal properties of DDR Si IMPATTs have also been studied at different mm-wave and THz frequencies. Large-signal simulation results show that DDR Si IMPATT is capable of delivering peak RF power of 633.69 mW with 7.95% conversion efficiency at 94 GHz for 50% voltage modulation, whereas peak RF power output and efficiency fall to 81.08 mW and 2.01% respectively at 0.5 THz for same voltage modulation. The simulation results are compared with the experimental results and are found to be in close agreement. (semiconductor devices)

  5. Complexity of EEG-signal in Time Domain - Possible Biomedical Application

    Science.gov (United States)

    Klonowski, Wlodzimierz; Olejarczyk, Elzbieta; Stepien, Robert

    2002-07-01

    Human brain is a highly complex nonlinear system. So it is not surprising that in analysis of EEG-signal, which represents overall activity of the brain, the methods of Nonlinear Dynamics (or Chaos Theory as it is commonly called) can be used. Even if the signal is not chaotic these methods are a motivating tool to explore changes in brain activity due to different functional activation states, e.g. different sleep stages, or to applied therapy, e.g. exposure to chemical agents (drugs) and physical factors (light, magnetic field). The methods supplied by Nonlinear Dynamics reveal signal characteristics that are not revealed by linear methods like FFT. Better understanding of principles that govern dynamics and complexity of EEG-signal can help to find `the signatures' of different physiological and pathological states of human brain, quantitative characteristics that may find applications in medical diagnostics.

  6. Phosphoproteomic profiling of in vivo signaling in liver by the mammalian target of rapamycin complex 1 (mTORC1.

    Directory of Open Access Journals (Sweden)

    Gokhan Demirkan

    Full Text Available Our understanding of signal transduction networks in the physiological context of an organism remains limited, partly due to the technical challenge of identifying serine/threonine phosphorylated peptides from complex tissue samples. In the present study, we focused on signaling through the mammalian target of rapamycin (mTOR complex 1 (mTORC1, which is at the center of a nutrient- and growth factor-responsive cell signaling network. Though studied extensively, the mechanisms involved in many mTORC1 biological functions remain poorly understood.We developed a phosphoproteomic strategy to purify, enrich and identify phosphopeptides from rat liver homogenates. Using the anticancer drug rapamycin, the only known target of which is mTORC1, we characterized signaling in liver from rats in which the complex was maximally activated by refeeding following 48 hr of starvation. Using protein and peptide fractionation methods, TiO(2 affinity purification of phosphopeptides and mass spectrometry, we reproducibly identified and quantified over four thousand phosphopeptides. Along with 5 known rapamycin-sensitive phosphorylation events, we identified 62 new rapamycin-responsive candidate phosphorylation sites. Among these were PRAS40, gephyrin, and AMP kinase 2. We observed similar proportions of increased and reduced phosphorylation in response to rapamycin. Gene ontology analysis revealed over-representation of mTOR pathway components among rapamycin-sensitive phosphopeptide candidates.In addition to identifying potential new mTORC1-mediated phosphorylation events, and providing information relevant to the biology of this signaling network, our experimental and analytical approaches indicate the feasibility of large-scale phosphoproteomic profiling of tissue samples to study physiological signaling events in vivo.

  7. Bio-Signal Complexity Analysis in Epileptic Seizure Monitoring: A Topic Review

    Directory of Open Access Journals (Sweden)

    Zhenning Mei

    2018-05-01

    Full Text Available Complexity science has provided new perspectives and opportunities for understanding a variety of complex natural or social phenomena, including brain dysfunctions like epilepsy. By delving into the complexity in electrophysiological signals and neuroimaging, new insights have emerged. These discoveries have revealed that complexity is a fundamental aspect of physiological processes. The inherent nonlinearity and non-stationarity of physiological processes limits the methods based on simpler underlying assumptions to point out the pathway to a more comprehensive understanding of their behavior and relation with certain diseases. The perspective of complexity may benefit both the research and clinical practice through providing novel data analytics tools devoted for the understanding of and the intervention about epilepsies. This review aims to provide a sketchy overview of the methods derived from different disciplines lucubrating to the complexity of bio-signals in the field of epilepsy monitoring. Although the complexity of bio-signals is still not fully understood, bundles of new insights have been already obtained. Despite the promising results about epileptic seizure detection and prediction through offline analysis, we are still lacking robust, tried-and-true real-time applications. Multidisciplinary collaborations and more high-quality data accessible to the whole community are needed for reproducible research and the development of such applications.

  8. Receptor density balances signal stimulation and attenuation in membrane-assembled complexes of bacterial chemotaxis signaling proteins

    Science.gov (United States)

    Besschetnova, Tatiana Y.; Montefusco, David J.; Asinas, Abdalin E.; Shrout, Anthony L.; Antommattei, Frances M.; Weis, Robert M.

    2008-01-01

    All cells possess transmembrane signaling systems that function in the environment of the lipid bilayer. In the Escherichia coli chemotaxis pathway, the binding of attractants to a two-dimensional array of receptors and signaling proteins simultaneously inhibits an associated kinase and stimulates receptor methylation—a slower process that restores kinase activity. These two opposing effects lead to robust adaptation toward stimuli through a physical mechanism that is not understood. Here, we provide evidence of a counterbalancing influence exerted by receptor density on kinase stimulation and receptor methylation. Receptor signaling complexes were reconstituted over a range of defined surface concentrations by using a template-directed assembly method, and the kinase and receptor methylation activities were measured. Kinase activity and methylation rates were both found to vary significantly with surface concentration—yet in opposite ways: samples prepared at high surface densities stimulated kinase activity more effectively than low-density samples, whereas lower surface densities produced greater methylation rates than higher densities. FRET experiments demonstrated that the cooperative change in kinase activity coincided with a change in the arrangement of the membrane-associated receptor domains. The counterbalancing influence of density on receptor methylation and kinase stimulation leads naturally to a model for signal regulation that is compatible with the known logic of the E. coli pathway. Density-dependent mechanisms are likely to be general and may operate when two or more membrane-related processes are influenced differently by the two-dimensional concentration of pathway elements. PMID:18711126

  9. Fuzzy approximate entropy analysis of chaotic and natural complex systems: detecting muscle fatigue using electromyography signals.

    Science.gov (United States)

    Xie, Hong-Bo; Guo, Jing-Yi; Zheng, Yong-Ping

    2010-04-01

    In the present contribution, a complexity measure is proposed to assess surface electromyography (EMG) in the study of muscle fatigue during sustained, isometric muscle contractions. Approximate entropy (ApEn) is believed to provide quantitative information about the complexity of experimental data that is often corrupted with noise, short data length, and in many cases, has inherent dynamics that exhibit both deterministic and stochastic behaviors. We developed an improved ApEn measure, i.e., fuzzy approximate entropy (fApEn), which utilizes the fuzzy membership function to define the vectors' similarity. Tests were conducted on independent, identically distributed (i.i.d.) Gaussian and uniform noises, a chirp signal, MIX processes, Rossler equation, and Henon map. Compared with the standard ApEn, the fApEn showed better monotonicity, relative consistency, and more robustness to noise when characterizing signals with different complexities. Performance analysis on experimental EMG signals demonstrated that the fApEn significantly decreased during the development of muscle fatigue, which is a similar trend to that of the mean frequency (MNF) of the EMG signal, while the standard ApEn failed to detect this change. Moreover, fApEn of EMG demonstrated a better robustness to the length of the analysis window in comparison with the MNF of EMG. The results suggest that the fApEn of an EMG signal may potentially become a new reliable method for muscle fatigue assessment and be applicable to other short noisy physiological signal analysis.

  10. The quantitative evaluation of complex defect signals from eddy current testings with multi-frequency methods

    International Nuclear Information System (INIS)

    Naegele, W.

    1982-01-01

    The usual formulation of multi-frequency eddy current signals of large defects by linearized impedance diagrams may lead to misinterpretations. Here a developement of the linear superposition principle is proposed, which takes into account also the curvature of the impedance diagrams thus allowing to identify even large defects in an unambiguous way. (orig.) [de

  11. Complex motion of a vehicle through a series of signals controlled by power-law phase

    Science.gov (United States)

    Nagatani, Takashi

    2017-07-01

    We study the dynamic motion of a vehicle moving through the series of traffic signals controlled by the position-dependent phase of power law. All signals are controlled by both cycle time and position-dependent phase. The dynamic model of the vehicular motion is described in terms of the nonlinear map. The vehicular motion varies in a complex manner by varying cycle time for various values of the power of the position-dependent phase. The vehicle displays the periodic motion with a long cycle for the integer power of the phase, while the vehicular motion exhibits the very complex behavior for the non-integer power of the phase.

  12. LASSIE: the large analogue signal and scaling information environment for FAIR

    International Nuclear Information System (INIS)

    Hoffmann, T.; Braeuning, H.; Haseitl, R.

    2012-01-01

    At FAIR, the Facility for Antiproton and Ion Research, several new accelerators and storage rings such as the SIS-100, HESR, CR, the inter-connecting HEBT beam lines, S-FRS and experiments will be built. All of these installations are equipped with beam diagnostic devices and other components, which deliver time-resolved analogue signals to show status, quality and performance of the accelerators. These signals can originate from particle detectors such as ionization chambers and plastic scintillators, but also from adapted output signals of transformers, collimators, magnet functions, RF cavities and others. To visualize and precisely correlate the time axis of all input signals a dedicated FESA based data acquisition and analysis system named LASSIE, the Large Analogue Signal and Scaling Information Environment, is currently being developed. The main operation mode of LASSIE is currently pulse counting with latching VME scaler boards. Later enhancements for ADC, QDC, or TDC digitization in the future are foreseen. The concept, features and challenges of this large distributed data acquisition system are presented. (authors)

  13. Synthesis of high-complexity rhythmic signals for closed-loop electrical neuromodulation.

    Science.gov (United States)

    Zalay, Osbert C; Bardakjian, Berj L

    2013-06-01

    We propose an approach to synthesizing high-complexity rhythmic signals for closed-loop electrical neuromodulation using cognitive rhythm generator (CRG) networks, wherein the CRG is a hybrid oscillator comprised of (1) a bank of neuronal modes, (2) a ring device (clock), and (3) a static output nonlinearity (mapper). Networks of coupled CRGs have been previously implemented to simulate the electrical activity of biological neural networks, including in silico models of epilepsy, producing outputs of similar waveform and complexity to the biological system. This has enabled CRG network models to be used as platforms for testing seizure control strategies. Presently, we take the application one step further, envisioning therapeutic CRG networks as rhythmic signal generators creating neuromimetic signals for stimulation purposes, motivated by recent research indicating that stimulus complexity and waveform characteristics influence neuromodulation efficacy. To demonstrate this concept, an epileptiform CRG network generating spontaneous seizure-like events (SLEs) was coupled to a therapeutic CRG network, forming a closed-loop neuromodulation system. SLEs are associated with low-complexity dynamics and high phase coherence in the network. The tuned therapeutic network generated a high-complexity, multi-banded rhythmic stimulation signal with prominent theta and gamma-frequency power that suppressed SLEs and increased dynamic complexity in the epileptiform network, as measured by a relative increase in the maximum Lyapunov exponent and decrease in phase coherence. CRG-based neuromodulation outperformed both low and high-frequency periodic pulse stimulation, suggesting that neuromodulation using complex, biomimetic signals may provide an improvement over conventional electrical stimulation techniques for treating neurological disorders such as epilepsy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. LC-MS/MS signal suppression effects in the analysis of pesticides in complex environmental matrices.

    Science.gov (United States)

    Choi, B K; Hercules, D M; Gusev, A I

    2001-02-01

    The application of LC separation and mobile phase additives in addressing LC-MS/MS matrix signal suppression effects for the analysis of pesticides in a complex environmental matrix was investigated. It was shown that signal suppression is most significant for analytes eluting early in the LC-MS analysis. Introduction of different buffers (e.g. ammonium formate, ammonium hydroxide, formic acid) into the LC mobile phase was effective in improving signal correlation between the matrix and standard samples. The signal improvement is dependent on buffer concentration as well as LC separation of the matrix components. The application of LC separation alone was not effective in addressing suppression effects when characterizing complex matrix samples. Overloading of the LC column by matrix components was found to significantly contribute to analyte-matrix co-elution and suppression of signal. This signal suppression effect can be efficiently compensated by 2D LC (LC-LC) separation techniques. The effectiveness of buffers and LC separation in improving signal correlation between standard and matrix samples is discussed.

  15. Use of multiple singular value decompositions to analyze complex intracellular calcium ion signals

    KAUST Repository

    Martinez, Josue G.

    2009-12-01

    We compare calcium ion signaling (Ca(2+)) between two exposures; the data are present as movies, or, more prosaically, time series of images. This paper describes novel uses of singular value decompositions (SVD) and weighted versions of them (WSVD) to extract the signals from such movies, in a way that is semi-automatic and tuned closely to the actual data and their many complexities. These complexities include the following. First, the images themselves are of no interest: all interest focuses on the behavior of individual cells across time, and thus, the cells need to be segmented in an automated manner. Second, the cells themselves have 100+ pixels, so that they form 100+ curves measured over time, so that data compression is required to extract the features of these curves. Third, some of the pixels in some of the cells are subject to image saturation due to bit depth limits, and this saturation needs to be accounted for if one is to normalize the images in a reasonably un-biased manner. Finally, the Ca(2+) signals have oscillations or waves that vary with time and these signals need to be extracted. Thus, our aim is to show how to use multiple weighted and standard singular value decompositions to detect, extract and clarify the Ca(2+) signals. Our signal extraction methods then lead to simple although finely focused statistical methods to compare Ca(2+) signals across experimental conditions.

  16. Large Signal Model of a Four-quadrant AC to DC Converter for Accelerator Magnets

    CERN Document Server

    De la Calle, R; Rinaldi, L; Völker, F V

    2001-01-01

    This paper presents the large signal model of a four-quadrant AC to DC converter, which is expected to be used in the area of particle accelerators. The system’s first stage is composed of a three-phase boost PWM (Pulse Width Modulated) rectifier with DSP (Digital Signal Processing) based power factor correction (PFC) and output voltage regulation. The second stage is a full-bridge PWM inverter that allows fast four-quadrant operation. The structure is fully reversible, and an additional resistance (brake chopper) is not needed to dissipate the energy when the beam deflection magnet acts as generator.

  17. Isolation and structure–function characterization of a signaling-active rhodopsin–G protein complex

    Science.gov (United States)

    Gao, Yang; Westfield, Gerwin; Erickson, Jon W.; Cerione, Richard A.; Skiniotis, Georgios; Ramachandran, Sekar

    2017-01-01

    The visual photo-transduction cascade is a prototypical G protein–coupled receptor (GPCR) signaling system, in which light-activated rhodopsin (Rho*) is the GPCR catalyzing the exchange of GDP for GTP on the heterotrimeric G protein transducin (GT). This results in the dissociation of GT into its component αT–GTP and β1γ1 subunit complex. Structural information for the Rho*–GT complex will be essential for understanding the molecular mechanism of visual photo-transduction. Moreover, it will shed light on how GPCRs selectively couple to and activate their G protein signaling partners. Here, we report on the preparation of a stable detergent-solubilized complex between Rho* and a heterotrimer (GT*) comprising a GαT/Gαi1 chimera (αT*) and β1γ1. The complex was formed on native rod outer segment membranes upon light activation, solubilized in lauryl maltose neopentyl glycol, and purified with a combination of affinity and size-exclusion chromatography. We found that the complex is fully functional and that the stoichiometry of Rho* to GαT* is 1:1. The molecular weight of the complex was calculated from small-angle X-ray scattering data and was in good agreement with a model consisting of one Rho* and one GT*. The complex was visualized by negative-stain electron microscopy, which revealed an architecture similar to that of the β2-adrenergic receptor–GS complex, including a flexible αT* helical domain. The stability and high yield of the purified complex should allow for further efforts toward obtaining a high-resolution structure of this important signaling complex. PMID:28655769

  18. Isolation and structure-function characterization of a signaling-active rhodopsin-G protein complex.

    Science.gov (United States)

    Gao, Yang; Westfield, Gerwin; Erickson, Jon W; Cerione, Richard A; Skiniotis, Georgios; Ramachandran, Sekar

    2017-08-25

    The visual photo-transduction cascade is a prototypical G protein-coupled receptor (GPCR) signaling system, in which light-activated rhodopsin (Rho*) is the GPCR catalyzing the exchange of GDP for GTP on the heterotrimeric G protein transducin (G T ). This results in the dissociation of G T into its component α T -GTP and β 1 γ 1 subunit complex. Structural information for the Rho*-G T complex will be essential for understanding the molecular mechanism of visual photo-transduction. Moreover, it will shed light on how GPCRs selectively couple to and activate their G protein signaling partners. Here, we report on the preparation of a stable detergent-solubilized complex between Rho* and a heterotrimer (G T *) comprising a Gα T /Gα i1 chimera (α T *) and β 1 γ 1 The complex was formed on native rod outer segment membranes upon light activation, solubilized in lauryl maltose neopentyl glycol, and purified with a combination of affinity and size-exclusion chromatography. We found that the complex is fully functional and that the stoichiometry of Rho* to Gα T * is 1:1. The molecular weight of the complex was calculated from small-angle X-ray scattering data and was in good agreement with a model consisting of one Rho* and one G T *. The complex was visualized by negative-stain electron microscopy, which revealed an architecture similar to that of the β 2 -adrenergic receptor-G S complex, including a flexible α T * helical domain. The stability and high yield of the purified complex should allow for further efforts toward obtaining a high-resolution structure of this important signaling complex. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. MacroBac: New Technologies for Robust and Efficient Large-Scale Production of Recombinant Multiprotein Complexes.

    Science.gov (United States)

    Gradia, Scott D; Ishida, Justin P; Tsai, Miaw-Sheue; Jeans, Chris; Tainer, John A; Fuss, Jill O

    2017-01-01

    Recombinant expression of large, multiprotein complexes is essential and often rate limiting for determining structural, biophysical, and biochemical properties of DNA repair, replication, transcription, and other key cellular processes. Baculovirus-infected insect cell expression systems are especially well suited for producing large, human proteins recombinantly, and multigene baculovirus systems have facilitated studies of multiprotein complexes. In this chapter, we describe a multigene baculovirus system called MacroBac that uses a Biobricks-type assembly method based on restriction and ligation (Series 11) or ligation-independent cloning (Series 438). MacroBac cloning and assembly is efficient and equally well suited for either single subcloning reactions or high-throughput cloning using 96-well plates and liquid handling robotics. MacroBac vectors are polypromoter with each gene flanked by a strong polyhedrin promoter and an SV40 poly(A) termination signal that minimize gene order expression level effects seen in many polycistronic assemblies. Large assemblies are robustly achievable, and we have successfully assembled as many as 10 genes into a single MacroBac vector. Importantly, we have observed significant increases in expression levels and quality of large, multiprotein complexes using a single, multigene, polypromoter virus rather than coinfection with multiple, single-gene viruses. Given the importance of characterizing functional complexes, we believe that MacroBac provides a critical enabling technology that may change the way that structural, biophysical, and biochemical research is done. © 2017 Elsevier Inc. All rights reserved.

  20. A functional TOC complex contributes to gravity signal transduction in Arabidopsis.

    Science.gov (United States)

    Strohm, Allison K; Barrett-Wilt, Greg A; Masson, Patrick H

    2014-01-01

    Although plastid sedimentation has long been recognized as important for a plant's perception of gravity, it was recently shown that plastids play an additional function in gravitropism. The Translocon at the Outer envelope membrane of Chloroplasts (TOC) complex transports nuclear-encoded proteins into plastids, and a receptor of this complex, Toc132, was previously hypothesized to contribute to gravitropism either by directly functioning as a gravity signal transducer or by indirectly mediating the plastid localization of a gravity signal transducer. Here we show that mutations in multiple genes encoding TOC complex components affect gravitropism in a genetically sensitized background and that the cytoplasmic acidic domain of Toc132 is not required for its involvement in this process. Furthermore, mutations in TOC132 enhance the gravitropic defect of a mutant whose amyloplasts lack starch. Finally, we show that the levels of several nuclear-encoded root proteins are altered in toc132 mutants. These data suggest that the TOC complex indirectly mediates gravity signal transduction in Arabidopsis and support the idea that plastids are involved in gravitropism not only through their ability to sediment but also as part of the signal transduction mechanism.

  1. Identifying deterministic signals in simulated gravitational wave data: algorithmic complexity and the surrogate data method

    International Nuclear Information System (INIS)

    Zhao Yi; Small, Michael; Coward, David; Howell, Eric; Zhao Chunnong; Ju Li; Blair, David

    2006-01-01

    We describe the application of complexity estimation and the surrogate data method to identify deterministic dynamics in simulated gravitational wave (GW) data contaminated with white and coloured noises. The surrogate method uses algorithmic complexity as a discriminating statistic to decide if noisy data contain a statistically significant level of deterministic dynamics (the GW signal). The results illustrate that the complexity method is sensitive to a small amplitude simulated GW background (SNR down to 0.08 for white noise and 0.05 for coloured noise) and is also more robust than commonly used linear methods (autocorrelation or Fourier analysis)

  2. NMR signal analysis in the large COMPASS $^{14}$NH$_{3}$ target

    CERN Document Server

    Koivuniemi, J; Hess, C; Kisselev, Y U; Meyer, W; Radtke, E; Reicherz, G; Doshita, N; Iwata, T; Kondo, K; Michigami, T

    2009-01-01

    In the large COMPASS polarized proton target the 1508 cm$^{3}$ of irradiated granular ammonia is polarized with dynamic nuclear polarization method using 4 mm microwaves in 2.5 T eld. The nuclear polarization up to 90 - 93 % is determined with cw NMR. The properties of the observed ammonia proton signals are described and spin thermodynamics in high elds is presented. Also the second moment of the NMR line is estimated.

  3. Analysis of the Influence of Complexity and Entropy of Odorant on Fractal Dynamics and Entropy of EEG Signal

    OpenAIRE

    Hamidreza Namazi; Amin Akrami; Sina Nazeri; Vladimir V. Kulish

    2016-01-01

    An important challenge in brain research is to make out the relation between the features of olfactory stimuli and the electroencephalogram (EEG) signal. Yet, no one has discovered any relation between the structures of olfactory stimuli and the EEG signal. This study investigates the relation between the structures of EEG signal and the olfactory stimulus (odorant). We show that the complexity of the EEG signal is coupled with the molecular complexity of the odorant, where more structurally ...

  4. Construction of large signaling pathways using an adaptive perturbation approach with phosphoproteomic data.

    Science.gov (United States)

    Melas, Ioannis N; Mitsos, Alexander; Messinis, Dimitris E; Weiss, Thomas S; Rodriguez, Julio-Saez; Alexopoulos, Leonidas G

    2012-04-01

    Construction of large and cell-specific signaling pathways is essential to understand information processing under normal and pathological conditions. On this front, gene-based approaches offer the advantage of large pathway exploration whereas phosphoproteomic approaches offer a more reliable view of pathway activities but are applicable to small pathway sizes. In this paper, we demonstrate an experimentally adaptive approach to construct large signaling pathways from phosphoproteomic data within a 3-day time frame. Our approach--taking advantage of the fast turnaround time of the xMAP technology--is carried out in four steps: (i) screen optimal pathway inducers, (ii) select the responsive ones, (iii) combine them in a combinatorial fashion to construct a phosphoproteomic dataset, and (iv) optimize a reduced generic pathway via an Integer Linear Programming formulation. As a case study, we uncover novel players and their corresponding pathways in primary human hepatocytes by interrogating the signal transduction downstream of 81 receptors of interest and constructing a detailed model for the responsive part of the network comprising 177 species (of which 14 are measured) and 365 interactions.

  5. Large signal S-parameters: modeling and radiation effects in microwave power transistors

    International Nuclear Information System (INIS)

    Graham, E.D. Jr.; Chaffin, R.J.; Gwyn, C.W.

    1973-01-01

    Microwave power transistors are usually characterized by measuring the source and load impedances, efficiency, and power output at a specified frequency and bias condition in a tuned circuit. These measurements provide limited data for circuit design and yield essentially no information concerning broadbanding possibilities. Recently, a method using large signal S-parameters has been developed which provides a rapid and repeatable means for measuring microwave power transistor parameters. These large signal S-parameters have been successfully used to design rf power amplifiers. Attempts at modeling rf power transistors have in the past been restricted to a modified Ebers-Moll procedure with numerous adjustable model parameters. The modified Ebers-Moll model is further complicated by inclusion of package parasitics. In the present paper an exact one-dimensional device analysis code has been used to model the performance of the transistor chip. This code has been integrated into the SCEPTRE circuit analysis code such that chip, package and circuit performance can be coupled together in the analysis. Using []his computational tool, rf transistor performance has been examined with particular attention given to the theoretical validity of large-signal S-parameters and the effects of nuclear radiation on device parameters. (auth)

  6. Nonlinear Vibration Signal Tracking of Large Offshore Bridge Stayed Cable Based on Particle Filter

    Directory of Open Access Journals (Sweden)

    Ye Qingwei

    2015-12-01

    Full Text Available The stayed cables are key stress components of large offshore bridge. The fault detection of stayed cable is very important for safe of large offshore bridge. A particle filter model and algorithm of nonlinear vibration signal are used in this paper. Firstly, the particle filter model of stayed cable of large offshore bridge is created. Nonlinear dynamic model of the stayed-cable and beam coupling system is dispersed in temporal dimension by using the finite difference method. The discrete nonlinear vibration equations of any cable element are worked out. Secondly, a state equation of particle filter is fitted by least square algorithm from the discrete nonlinear vibration equations. So the particle filter algorithm can use the accurate state equations. Finally, the particle filter algorithm is used to filter the vibration signal of bridge stayed cable. According to the particle filter, the de-noised vibration signal can be tracked and be predicted for a short time accurately. Many experiments are done at some actual bridges. The simulation experiments and the actual experiments on the bridge stayed cables are all indicating that the particle filter algorithm in this paper has good performance and works stably.

  7. Stream computing for biomedical signal processing: A QRS complex detection case-study.

    Science.gov (United States)

    Murphy, B M; O'Driscoll, C; Boylan, G B; Lightbody, G; Marnane, W P

    2015-01-01

    Recent developments in "Big Data" have brought significant gains in the ability to process large amounts of data on commodity server hardware. Stream computing is a relatively new paradigm in this area, addressing the need to process data in real time with very low latency. While this approach has been developed for dealing with large scale data from the world of business, security and finance, there is a natural overlap with clinical needs for physiological signal processing. In this work we present a case study of streams processing applied to a typical physiological signal processing problem: QRS detection from ECG data.

  8. Understanding large multiprotein complexes: applying a multiple allosteric networks model to explain the function of the Mediator transcription complex.

    Science.gov (United States)

    Lewis, Brian A

    2010-01-15

    The regulation of transcription and of many other cellular processes involves large multi-subunit protein complexes. In the context of transcription, it is known that these complexes serve as regulatory platforms that connect activator DNA-binding proteins to a target promoter. However, there is still a lack of understanding regarding the function of these complexes. Why do multi-subunit complexes exist? What is the molecular basis of the function of their constituent subunits, and how are these subunits organized within a complex? What is the reason for physical connections between certain subunits and not others? In this article, I address these issues through a model of network allostery and its application to the eukaryotic RNA polymerase II Mediator transcription complex. The multiple allosteric networks model (MANM) suggests that protein complexes such as Mediator exist not only as physical but also as functional networks of interconnected proteins through which information is transferred from subunit to subunit by the propagation of an allosteric state known as conformational spread. Additionally, there are multiple distinct sub-networks within the Mediator complex that can be defined by their connections to different subunits; these sub-networks have discrete functions that are activated when specific subunits interact with other activator proteins.

  9. Large Variability in the Diversity of Physiologically Complex Surgical Procedures Exists Nationwide Among All Hospitals Including Among Large Teaching Hospitals.

    Science.gov (United States)

    Dexter, Franklin; Epstein, Richard H; Thenuwara, Kokila; Lubarsky, David A

    2017-11-22

    Multiple previous studies have shown that having a large diversity of procedures has a substantial impact on quality management of hospital surgical suites. At hospitals with substantial diversity, unless sophisticated statistical methods suitable for rare events are used, anesthesiologists working in surgical suites will have inaccurate predictions of surgical blood usage, case durations, cost accounting and price transparency, times remaining in late running cases, and use of intraoperative equipment. What is unknown is whether large diversity is a feature of only a few very unique set of hospitals nationwide (eg, the largest hospitals in each state or province). The 2013 United States Nationwide Readmissions Database was used to study heterogeneity among 1981 hospitals in their diversities of physiologically complex surgical procedures (ie, the procedure codes). The diversity of surgical procedures performed at each hospital was quantified using a summary measure, the number of different physiologically complex surgical procedures commonly performed at the hospital (ie, 1/Herfindahl). A total of 53.9% of all hospitals commonly performed 3-fold larger diversity (ie, >30 commonly performed physiologically complex procedures). Larger hospitals had greater diversity than the small- and medium-sized hospitals (P 30 procedures (lower 99% CL, 71.9% of hospitals). However, there was considerable variability among the large teaching hospitals in their diversity (interquartile range of the numbers of commonly performed physiologically complex procedures = 19.3; lower 99% CL, 12.8 procedures). The diversity of procedures represents a substantive differentiator among hospitals. Thus, the usefulness of statistical methods for operating room management should be expected to be heterogeneous among hospitals. Our results also show that "large teaching hospital" alone is an insufficient description for accurate prediction of the extent to which a hospital sustains the

  10. Defining Execution Viewpoints for a Large and Complex Software-Intensive System

    OpenAIRE

    Callo Arias, Trosky B.; America, Pierre; Avgeriou, Paris

    2009-01-01

    An execution view is an important asset for developing large and complex systems. An execution view helps practitioners to describe, analyze, and communicate what a software system does at runtime and how it does it. In this paper, we present an approach to define execution viewpoints for an existing large and complex software-intensive system. This definition approach enables the customization and extension of a set of predefined viewpoints to address the requirements of a specific developme...

  11. Automated X-ray television complex for testing large dynamic objects

    International Nuclear Information System (INIS)

    Gusev, E.A.; Luk'yanenko, Eh.A.; Chelnokov, V.B.; Kuleshov, V.K.; Alkhimov, Yu.V.

    1992-01-01

    An automated X-ray television complex on the base of matrix gas-dischage large-area (2.1x1.0 m) converter for testing large cargoes and containers, as well as for inductrial article diagnostics is described. The complex pulsed operation with the 512 kbytes television digital memory unit provides for testing dynamic objects under minimal doses (20-100 μR)

  12. Large Complex Odontoma of Mandible in a Young Boy: A Rare and Unusual Case Report

    Directory of Open Access Journals (Sweden)

    G. Siva Prasad Reddy

    2014-01-01

    Full Text Available Odontomas are the most common odontogenic tumors. They are broadly classified in to Compound Odontoma and Complex Odontoma. Among them complex odontoma is a rare tumor. Occasionally this tumor becomes large, causing expansion of bone followed by facial asymmetry. Otherwise these tumors are asymptomatic and are generally diagnosed on radiographic examination. We report a rare case of complex odontoma of mandible in a young boy. The tumor was treated by surgical excision under general anesthesia.

  13. Disentangling the Complexity of HGF Signaling by Combining Qualitative and Quantitative Modeling.

    Directory of Open Access Journals (Sweden)

    Lorenza A D'Alessandro

    2015-04-01

    Full Text Available Signaling pathways are characterized by crosstalk, feedback and feedforward mechanisms giving rise to highly complex and cell-context specific signaling networks. Dissecting the underlying relations is crucial to predict the impact of targeted perturbations. However, a major challenge in identifying cell-context specific signaling networks is the enormous number of potentially possible interactions. Here, we report a novel hybrid mathematical modeling strategy to systematically unravel hepatocyte growth factor (HGF stimulated phosphoinositide-3-kinase (PI3K and mitogen activated protein kinase (MAPK signaling, which critically contribute to liver regeneration. By combining time-resolved quantitative experimental data generated in primary mouse hepatocytes with interaction graph and ordinary differential equation modeling, we identify and experimentally validate a network structure that represents the experimental data best and indicates specific crosstalk mechanisms. Whereas the identified network is robust against single perturbations, combinatorial inhibition strategies are predicted that result in strong reduction of Akt and ERK activation. Thus, by capitalizing on the advantages of the two modeling approaches, we reduce the high combinatorial complexity and identify cell-context specific signaling networks.

  14. A High Density Low Cost Digital Signal Processing Module for Large Scale Radiation Detectors

    International Nuclear Information System (INIS)

    Tan, Hui; Hennig, Wolfgang; Walby, Mark D.; Breus, Dimitry; Harris, Jackson T.; Grudberg, Peter M.; Warburton, William K.

    2013-06-01

    A 32-channel digital spectrometer PIXIE-32 is being developed for nuclear physics or other radiation detection applications requiring digital signal processing with large number of channels at relatively low cost. A single PIXIE-32 provides spectrometry and waveform acquisition for 32 input signals per module whereas multiple modules can be combined into larger systems. It is based on the PCI Express standard which allows data transfer rates to the host computer of up to 800 MB/s. Each of the 32 channels in a PIXIE-32 module accepts signals directly from a detector preamplifier or photomultiplier. Digitally controlled offsets can be individually adjusted for each channel. Signals are digitized in 12-bit, 50 MHz multi-channel ADCs. Triggering, pile-up inspection and filtering of the data stream are performed in real time, and pulse heights and other event data are calculated on an event-by event basis. The hardware architecture, internal and external triggering features, and the spectrometry and waveform acquisition capability of the PIXIE- 32 as well as its capability to distribute clock and triggers among multiple modules, are presented. (authors)

  15. Comparison of GFL–GFRα complexes: further evidence relating GFL bend angle to RET signalling

    International Nuclear Information System (INIS)

    Parkash, Vimal; Goldman, Adrian

    2009-01-01

    The second crystal structure of the GDNF-GFRα1 complex provides further evidence that GFL signalling through RET is determined by the bend angle in the GFL. Glial cell line-derived neurotrophic factor (GDNF) activates the receptor tyrosine kinase RET by binding to the GDNF-family receptor α1 (GFRα1) and forming the GDNF 2 –GFRα1 2 –RET 2 heterohexamer complex. A previous crystal structure of the GDNF 2 –GFRα1 2 complex suggested that differences in signalling in GDNF-family ligand (GFL) complexes might arise from differences in the bend angle between the two monomers in the GFL homodimer. Here, a 2.35 Å resolution structure of the GDNF 2 –GFRα1 2 complex crystallized with new cell dimensions is reported. The structure was refined to a final R factor of 22.5% (R free = 28%). The structures of both biological tetrameric complexes in the asymmetric unit are very similar to 2v5e and different from the artemin–GFRα3 structure, even though there is a small change in the structure of the GDNF. By comparison of all known GDNF and artemin structures, it is concluded that GDNF is more bent and more flexible than artemin and that this may be related to RET signalling. Comparisons also suggest that the differences between artemin and GDNF arise from the increased curvature of the artemin ‘fingers’, which both increases the buried surface area in the monomer–monomer interface and changes the intermonomer bend angle. From sequence comparison, it is suggested that neuturin (the second GFL) adopts an artemin-like conformation, while persephin has a different conformation to the other three

  16. Binding of the Ras activator son of sevenless to insulin receptor substrate-1 signaling complexes.

    Science.gov (United States)

    Baltensperger, K; Kozma, L M; Cherniack, A D; Klarlund, J K; Chawla, A; Banerjee, U; Czech, M P

    1993-06-25

    Signal transmission by insulin involves tyrosine phosphorylation of a major insulin receptor substrate (IRS-1) and exchange of Ras-bound guanosine diphosphate for guanosine triphosphate. Proteins containing Src homology 2 and 3 (SH2 and SH3) domains, such as the p85 regulatory subunit of phosphatidylinositol-3 kinase and growth factor receptor-bound protein 2 (GRB2), bind tyrosine phosphate sites on IRS-1 through their SH2 regions. Such complexes in COS cells were found to contain the heterologously expressed putative guanine nucleotide exchange factor encoded by the Drosophila son of sevenless gene (dSos). Thus, GRB2, p85, or other proteins with SH2-SH3 adapter sequences may link Sos proteins to IRS-1 signaling complexes as part of the mechanism by which insulin activates Ras.

  17. Characterizing scaling properties of complex signals with missed data segments using the multifractal analysis

    Science.gov (United States)

    Pavlov, A. N.; Pavlova, O. N.; Abdurashitov, A. S.; Sindeeva, O. A.; Semyachkina-Glushkovskaya, O. V.; Kurths, J.

    2018-01-01

    The scaling properties of complex processes may be highly influenced by the presence of various artifacts in experimental recordings. Their removal produces changes in the singularity spectra and the Hölder exponents as compared with the original artifacts-free data, and these changes are significantly different for positively correlated and anti-correlated signals. While signals with power-law correlations are nearly insensitive to the loss of significant parts of data, the removal of fragments of anti-correlated signals is more crucial for further data analysis. In this work, we study the ability of characterizing scaling features of chaotic and stochastic processes with distinct correlation properties using a wavelet-based multifractal analysis, and discuss differences between the effect of missed data for synchronous and asynchronous oscillatory regimes. We show that even an extreme data loss allows characterizing physiological processes such as the cerebral blood flow dynamics.

  18. Discrimination of Rock Fracture and Blast Events Based on Signal Complexity and Machine Learning

    Directory of Open Access Journals (Sweden)

    Zilong Zhou

    2018-01-01

    Full Text Available The automatic discrimination of rock fracture and blast events is complex and challenging due to the similar waveform characteristics. To solve this problem, a new method based on the signal complexity analysis and machine learning has been proposed in this paper. First, the permutation entropy values of signals at different scale factors are calculated to reflect complexity of signals and constructed into a feature vector set. Secondly, based on the feature vector set, back-propagation neural network (BPNN as a means of machine learning is applied to establish a discriminator for rock fracture and blast events. Then to evaluate the classification performances of the new method, the classifying accuracies of support vector machine (SVM, naive Bayes classifier, and the new method are compared, and the receiver operating characteristic (ROC curves are also analyzed. The results show the new method obtains the best classification performances. In addition, the influence of different scale factor q and number of training samples n on discrimination results is discussed. It is found that the classifying accuracy of the new method reaches the highest value when q = 8–15 or 8–20 and n=140.

  19. Biogenesis of the mitochondrial TOM complex: Mim1 promotes insertion and assembly of signal-anchored receptors.

    Science.gov (United States)

    Becker, Thomas; Pfannschmidt, Sylvia; Guiard, Bernard; Stojanovski, Diana; Milenkovic, Dusanka; Kutik, Stephan; Pfanner, Nikolaus; Meisinger, Chris; Wiedemann, Nils

    2008-01-04

    The translocase of the outer membrane (TOM complex) is the central entry gate for nuclear-encoded mitochondrial precursor proteins. All Tom proteins are also encoded by nuclear genes and synthesized as precursors in the cytosol. The channel-forming beta-barrel protein Tom40 is targeted to mitochondria via Tom receptors and inserted into the outer membrane by the sorting and assembly machinery (SAM complex). A further outer membrane protein, Mim1, plays a less defined role in assembly of Tom40 into the TOM complex. The three receptors Tom20, Tom22, and Tom70 are anchored in the outer membrane by a single transmembrane alpha-helix, located at the N terminus in the case of Tom20 and Tom70 (signal-anchored) or in the C-terminal portion in the case of Tom22 (tail-anchored). Insertion of the precursor of Tom22 into the outer membrane requires pre-existing Tom receptors while the import pathway of the precursors of Tom20 and Tom70 is only poorly understood. We report that Mim1 is required for efficient membrane insertion and assembly of Tom20 and Tom70, but not Tom22. We show that Mim1 associates with SAM(core) components to a large SAM complex, explaining its role in late steps of the assembly pathway of Tom40. We conclude that Mim1 is not only required for biogenesis of the beta-barrel protein Tom40 but also for membrane insertion and assembly of signal-anchored Tom receptors. Thus, Mim1 plays an important role in the efficient assembly of the mitochondrial TOM complex.

  20. Large-signal, dynamic simulation of the slowpoke-3 nuclear heating reactor

    International Nuclear Information System (INIS)

    Tseng, C.M.; Lepp, R.M.

    1983-07-01

    A 2 MWt nuclear reactor, called SLOWPOKE-3, is being developed at the Chalk River Nuclear Laboratories (CRNL). This reactor, which is cooled by natural circulation, is designed to produce hot water for commercial space heating and perhaps generate some electricity in remote locations where the costs of alternate forms of energy are high. A large-signal, dynamic simulation of this reactor, without closed-loop control, was developed and implemented on a hybrid computer, using the basic equations of conservation of mass, energy and momentum. The natural circulation of downcomer flow in the pool was simulated using a special filter, capable of modelling various flow conditions. The simulation was then used to study the intermediate and long-term transient response of SLOWPOKE-3 to large disturbances, such as loss of heat sink, loss of regulation, daily load following, and overcooling of the reactor coolant. Results of the simulation show that none of these disturbances produce hazardous transients

  1. Signals of doubly-charged Higgsinos at the CERN Large Hadron Collider

    International Nuclear Information System (INIS)

    Demir, Durmus A.; Frank, Mariana; Turan, Ismail; Huitu, Katri; Rai, Santosh Kumar

    2008-01-01

    Several supersymmetric models with extended gauge structures, motivated by either grand unification or by neutrino mass generation, predict light doubly-charged Higgsinos. In this work we study productions and decays of doubly-charged Higgsinos present in left-right supersymmetric models, and show that they invariably lead to novel collider signals not found in the minimal supersymmetric model or in any of its extensions motivated by the μ problem or even in extra dimensional theories. We investigate their distinctive signatures at the Large Hadron Collider in both pair- and single-production modes, and show that they are powerful tools in determining the underlying model via the measurements at the Large Hadron Collider experiments.

  2. Large scale statistical inference of signaling pathways from RNAi and microarray data

    Directory of Open Access Journals (Sweden)

    Poustka Annemarie

    2007-10-01

    Full Text Available Abstract Background The advent of RNA interference techniques enables the selective silencing of biologically interesting genes in an efficient way. In combination with DNA microarray technology this enables researchers to gain insights into signaling pathways by observing downstream effects of individual knock-downs on gene expression. These secondary effects can be used to computationally reverse engineer features of the upstream signaling pathway. Results In this paper we address this challenging problem by extending previous work by Markowetz et al., who proposed a statistical framework to score networks hypotheses in a Bayesian manner. Our extensions go in three directions: First, we introduce a way to omit the data discretization step needed in the original framework via a calculation based on p-values instead. Second, we show how prior assumptions on the network structure can be incorporated into the scoring scheme using regularization techniques. Third and most important, we propose methods to scale up the original approach, which is limited to around 5 genes, to large scale networks. Conclusion Comparisons of these methods on artificial data are conducted. Our proposed module network is employed to infer the signaling network between 13 genes in the ER-α pathway in human MCF-7 breast cancer cells. Using a bootstrapping approach this reconstruction can be found with good statistical stability. The code for the module network inference method is available in the latest version of the R-package nem, which can be obtained from the Bioconductor homepage.

  3. TOR Complex 2-Ypk1 Signaling Maintains Sphingolipid Homeostasis by Sensing and Regulating ROS Accumulation

    Directory of Open Access Journals (Sweden)

    Brad J. Niles

    2014-02-01

    Full Text Available Reactive oxygen species (ROS are produced during normal metabolism and can function as signaling molecules. However, ROS at elevated levels can damage cells. Here, we identify the conserved target of rapamycin complex 2 (TORC2/Ypk1 signaling module as an important regulator of ROS in the model eukaryotic organism, S. cerevisiae. We show that TORC2/Ypk1 suppresses ROS produced both by mitochondria as well as by nonmitochondrial sources, including changes in acidification of the vacuole. Furthermore, we link vacuole-related ROS to sphingolipids, essential components of cellular membranes, whose synthesis is also controlled by TORC2/Ypk1 signaling. In total, our data reveal that TORC2/Ypk1 act within a homeostatic feedback loop to maintain sphingolipid levels and that ROS are a critical regulatory signal within this system. Thus, ROS sensing and signaling by TORC2/Ypk1 play a central physiological role in sphingolipid biosynthesis and in the maintenance of cell growth and viability.

  4. Precise signal amplitude retrieval for a non-homogeneous diagnostic beam using complex interferometry approach

    Science.gov (United States)

    Krupka, M.; Kalal, M.; Dostal, J.; Dudzak, R.; Juha, L.

    2017-08-01

    Classical interferometry became widely used method of active optical diagnostics. Its more advanced version, allowing reconstruction of three sets of data from just one especially designed interferogram (so called complex interferogram) was developed in the past and became known as complex interferometry. Along with the phase shift, which can be also retrieved using classical interferometry, the amplitude modifications of the probing part of the diagnostic beam caused by the object under study (to be called the signal amplitude) as well as the contrast of the interference fringes can be retrieved using the complex interferometry approach. In order to partially compensate for errors in the reconstruction due to imperfections in the diagnostic beam intensity structure as well as for errors caused by a non-ideal optical setup of the interferometer itself (including the quality of its optical components), a reference interferogram can be put to a good use. This method of interferogram analysis of experimental data has been successfully implemented in practice. However, in majority of interferometer setups (especially in the case of the ones employing the wavefront division) the probe and the reference part of the diagnostic beam would feature different intensity distributions over their respective cross sections. This introduces additional error into the reconstruction of the signal amplitude and the fringe contrast, which cannot be resolved using the reference interferogram only. In order to deal with this error it was found that additional separately recorded images of the intensity distribution of the probe and the reference part of the diagnostic beam (with no signal present) are needed. For the best results a sufficient shot-to-shot stability of the whole diagnostic system is required. In this paper, efficiency of the complex interferometry approach for obtaining the highest possible accuracy of the signal amplitude reconstruction is verified using the computer

  5. Large-signal modulation characteristics of a GaN-based micro-LED for Gbps visible-light communication

    Science.gov (United States)

    Tian, Pengfei; Wu, Zhengyuan; Liu, Xiaoyan; Fang, Zhilai; Zhang, Shuailong; Zhou, Xiaolin; Liu, Kefu; Liu, Ming-Gang; Chen, Shu-Jhih; Lee, Chia-Yu; Cong, Chunxiao; Hu, Laigui; Qiu, Zhi-Jun; Zheng, Lirong; Liu, Ran

    2018-04-01

    The large-signal modulation characteristics of a GaN-based micro-LED have been studied for Gbps visible-light communication. With an increasing signal modulation depth the modulation bandwidth decreases, which matches up with the increase in the sum of the signal rise time and fall time. By simulating the band diagram and the carrier recombination rate of the micro-LED under large-signal modulation, carrier recombination and the carrier sweep-out effect are analyzed and found to be the dominant mechanisms behind the variation of modulation bandwidth. These results give further insight into improving the modulation bandwidth for high-speed visible-light communication.

  6. Nitric Oxide Synthase and Cyclooxygenase Pathways: A Complex Interplay in Cellular Signaling.

    Science.gov (United States)

    Sorokin, Andrey

    2016-01-01

    The cellular reaction to external challenges is a tightly regulated process consisting of integrated processes mediated by a variety of signaling molecules, generated as a result of modulation of corresponding biosynthetic systems. Both, nitric oxide synthase (NOS) and cyclooxygenase (COX) systems, consist of constitutive forms (NOS1, NOS3 and COX-1), which are mostly involved in housekeeping tasks, and inducible forms (NOS2 and COX-2), which shape the cellular response to stress and variety of bioactive agents. The complex interplay between NOS and COX pathways can be observed at least at three levels. Firstly, products of NOS and Cox systems can mediate the regulation and the expression of inducible forms (NOS2 and COX-2) in response of similar and dissimilar stimulus. Secondly, the reciprocal modulation of cyclooxygenase activity by nitric oxide and NOS activity by prostaglandins at the posttranslational level has been shown to occur. Mechanisms by which nitric oxide can modulate prostaglandin synthesis include direct S-nitrosylation of COX and inactivation of prostaglandin I synthase by peroxynitrite, product of superoxide reaction with nitric oxide. Prostaglandins, conversely, can promote an increased association of dynein light chain (DLC) (also known as protein inhibitor of neuronal nitric oxide synthase) with NOS1, thereby reducing its activity. The third level of interplay is provided by intracellular crosstalk of signaling pathways stimulated by products of NOS and COX which contributes significantly to the complexity of cellular signaling. Since modulation of COX and NOS pathways was shown to be principally involved in a variety of pathological conditions, the dissection of their complex relationship is needed for better understanding of possible therapeutic strategies. This review focuses on implications of interplay between NOS and COX for cellular function and signal integration.

  7. Hurst Exponent Analysis of Resting-State fMRI Signal Complexity across the Adult Lifespan

    Directory of Open Access Journals (Sweden)

    Jianxin Dong

    2018-02-01

    Full Text Available Exploring functional information among various brain regions across time enables understanding of healthy aging process and holds great promise for age-related brain disease diagnosis. This paper proposed a method to explore fractal complexity of the resting-state functional magnetic resonance imaging (rs-fMRI signal in the human brain across the adult lifespan using Hurst exponent (HE. We took advantage of the examined rs-fMRI data from 116 adults 19 to 85 years of age (44.3 ± 19.4 years, 49 females from NKI/Rockland sample. Region-wise and voxel-wise analyses were performed to investigate the effects of age, gender, and their interaction on complexity. In region-wise analysis, we found that the healthy aging is accompanied by a loss of complexity in frontal and parietal lobe and increased complexity in insula, limbic, and temporal lobe. Meanwhile, differences in HE between genders were found to be significant in parietal lobe (p = 0.04, corrected. However, there was no interaction between gender and age. In voxel-wise analysis, the significant complexity decrease with aging was found in frontal and parietal lobe, and complexity increase was found in insula, limbic lobe, occipital lobe, and temporal lobe with aging. Meanwhile, differences in HE between genders were found to be significant in frontal, parietal, and limbic lobe. Furthermore, we found age and sex interaction in right parahippocampal gyrus (p = 0.04, corrected. Our findings reveal HE variations of the rs-fMRI signal across the human adult lifespan and show that HE may serve as a new parameter to assess healthy aging process.

  8. Microscopic insight into thermodynamics of conformational changes of SAP-SLAM complex in signal transduction cascade

    Science.gov (United States)

    Samanta, Sudipta; Mukherjee, Sanchita

    2017-04-01

    The signalling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, associate with SLAM-associated protein (SAP)-related molecules, composed of single SH2 domain architecture. SAP activates Src-family kinase Fyn after SLAM ligation, resulting in a SLAM-SAP-Fyn complex, where, SAP binds the Fyn SH3 domain that does not involve canonical SH3 or SH2 interactions. This demands insight into this SAP mediated signalling cascade. Thermodynamics of the conformational changes are extracted from the histograms of dihedral angles obtained from the all-atom molecular dynamics simulations of this structurally well characterized SAP-SLAM complex. The results incorporate the binding induced thermodynamic changes of individual amino acid as well as the secondary structural elements of the protein and the solvent. Stabilization of the peptide partially comes through a strong hydrogen bonding network with the protein, while hydrophobic interactions also play a significant role where the peptide inserts itself into a hydrophobic cavity of the protein. SLAM binding widens SAP's second binding site for Fyn, which is the next step in the signal transduction cascade. The higher stabilization and less fluctuation of specific residues of SAP in the Fyn binding site, induced by SAP-SLAM complexation, emerge as the key structural elements to trigger the recognition of SAP by the SH3 domain of Fyn. The thermodynamic quantification of the protein due to complexation not only throws deeper understanding in the established mode of SAP-SLAM interaction but also assists in the recognition of the relevant residues of the protein responsible for alterations in its activity.

  9. Optimal number of coarse-grained sites in different components of large biomolecular complexes.

    Science.gov (United States)

    Sinitskiy, Anton V; Saunders, Marissa G; Voth, Gregory A

    2012-07-26

    The computational study of large biomolecular complexes (molecular machines, cytoskeletal filaments, etc.) is a formidable challenge facing computational biophysics and biology. To achieve biologically relevant length and time scales, coarse-grained (CG) models of such complexes usually must be built and employed. One of the important early stages in this approach is to determine an optimal number of CG sites in different constituents of a complex. This work presents a systematic approach to this problem. First, a universal scaling law is derived and numerically corroborated for the intensity of the intrasite (intradomain) thermal fluctuations as a function of the number of CG sites. Second, this result is used for derivation of the criterion for the optimal number of CG sites in different parts of a large multibiomolecule complex. In the zeroth-order approximation, this approach validates the empirical rule of taking one CG site per fixed number of atoms or residues in each biomolecule, previously widely used for smaller systems (e.g., individual biomolecules). The first-order corrections to this rule are derived and numerically checked by the case studies of the Escherichia coli ribosome and Arp2/3 actin filament junction. In different ribosomal proteins, the optimal number of amino acids per CG site is shown to differ by a factor of 3.5, and an even wider spread may exist in other large biomolecular complexes. Therefore, the method proposed in this paper is valuable for the optimal construction of CG models of such complexes.

  10. Communication efficiency and congestion of signal traffic in large-scale brain networks.

    Science.gov (United States)

    Mišić, Bratislav; Sporns, Olaf; McIntosh, Anthony R

    2014-01-01

    The complex connectivity of the cerebral cortex suggests that inter-regional communication is a primary function. Using computational modeling, we show that anatomical connectivity may be a major determinant for global information flow in brain networks. A macaque brain network was implemented as a communication network in which signal units flowed between grey matter nodes along white matter paths. Compared to degree-matched surrogate networks, information flow on the macaque brain network was characterized by higher loss rates, faster transit times and lower throughput, suggesting that neural connectivity may be optimized for speed rather than fidelity. Much of global communication was mediated by a "rich club" of hub regions: a sub-graph comprised of high-degree nodes that are more densely interconnected with each other than predicted by chance. First, macaque communication patterns most closely resembled those observed for a synthetic rich club network, but were less similar to those seen in a synthetic small world network, suggesting that the former is a more fundamental feature of brain network topology. Second, rich club regions attracted the most signal traffic and likewise, connections between rich club regions carried more traffic than connections between non-rich club regions. Third, a number of rich club regions were significantly under-congested, suggesting that macaque connectivity actively shapes information flow, funneling traffic towards some nodes and away from others. Together, our results indicate a critical role of the rich club of hub nodes in dynamic aspects of global brain communication.

  11. Protein complex prediction in large ontology attributed protein-protein interaction networks.

    Science.gov (United States)

    Zhang, Yijia; Lin, Hongfei; Yang, Zhihao; Wang, Jian; Li, Yanpeng; Xu, Bo

    2013-01-01

    Protein complexes are important for unraveling the secrets of cellular organization and function. Many computational approaches have been developed to predict protein complexes in protein-protein interaction (PPI) networks. However, most existing approaches focus mainly on the topological structure of PPI networks, and largely ignore the gene ontology (GO) annotation information. In this paper, we constructed ontology attributed PPI networks with PPI data and GO resource. After constructing ontology attributed networks, we proposed a novel approach called CSO (clustering based on network structure and ontology attribute similarity). Structural information and GO attribute information are complementary in ontology attributed networks. CSO can effectively take advantage of the correlation between frequent GO annotation sets and the dense subgraph for protein complex prediction. Our proposed CSO approach was applied to four different yeast PPI data sets and predicted many well-known protein complexes. The experimental results showed that CSO was valuable in predicting protein complexes and achieved state-of-the-art performance.

  12. Identification of Anisomerous Motor Imagery EEG Signals Based on Complex Algorithms

    Science.gov (United States)

    Zhang, Zhiwen; Duan, Feng; Zhou, Xin; Meng, Zixuan

    2017-01-01

    Motor imagery (MI) electroencephalograph (EEG) signals are widely applied in brain-computer interface (BCI). However, classified MI states are limited, and their classification accuracy rates are low because of the characteristics of nonlinearity and nonstationarity. This study proposes a novel MI pattern recognition system that is based on complex algorithms for classifying MI EEG signals. In electrooculogram (EOG) artifact preprocessing, band-pass filtering is performed to obtain the frequency band of MI-related signals, and then, canonical correlation analysis (CCA) combined with wavelet threshold denoising (WTD) is used for EOG artifact preprocessing. We propose a regularized common spatial pattern (R-CSP) algorithm for EEG feature extraction by incorporating the principle of generic learning. A new classifier combining the K-nearest neighbor (KNN) and support vector machine (SVM) approaches is used to classify four anisomerous states, namely, imaginary movements with the left hand, right foot, and right shoulder and the resting state. The highest classification accuracy rate is 92.5%, and the average classification accuracy rate is 87%. The proposed complex algorithm identification method can significantly improve the identification rate of the minority samples and the overall classification performance. PMID:28874909

  13. Identification of Anisomerous Motor Imagery EEG Signals Based on Complex Algorithms.

    Science.gov (United States)

    Liu, Rensong; Zhang, Zhiwen; Duan, Feng; Zhou, Xin; Meng, Zixuan

    2017-01-01

    Motor imagery (MI) electroencephalograph (EEG) signals are widely applied in brain-computer interface (BCI). However, classified MI states are limited, and their classification accuracy rates are low because of the characteristics of nonlinearity and nonstationarity. This study proposes a novel MI pattern recognition system that is based on complex algorithms for classifying MI EEG signals. In electrooculogram (EOG) artifact preprocessing, band-pass filtering is performed to obtain the frequency band of MI-related signals, and then, canonical correlation analysis (CCA) combined with wavelet threshold denoising (WTD) is used for EOG artifact preprocessing. We propose a regularized common spatial pattern (R-CSP) algorithm for EEG feature extraction by incorporating the principle of generic learning. A new classifier combining the K -nearest neighbor (KNN) and support vector machine (SVM) approaches is used to classify four anisomerous states, namely, imaginary movements with the left hand, right foot, and right shoulder and the resting state. The highest classification accuracy rate is 92.5%, and the average classification accuracy rate is 87%. The proposed complex algorithm identification method can significantly improve the identification rate of the minority samples and the overall classification performance.

  14. Analysis of the Influence of Complexity and Entropy of Odorant on Fractal Dynamics and Entropy of EEG Signal.

    Science.gov (United States)

    Namazi, Hamidreza; Akrami, Amin; Nazeri, Sina; Kulish, Vladimir V

    2016-01-01

    An important challenge in brain research is to make out the relation between the features of olfactory stimuli and the electroencephalogram (EEG) signal. Yet, no one has discovered any relation between the structures of olfactory stimuli and the EEG signal. This study investigates the relation between the structures of EEG signal and the olfactory stimulus (odorant). We show that the complexity of the EEG signal is coupled with the molecular complexity of the odorant, where more structurally complex odorant causes less fractal EEG signal. Also, odorant having higher entropy causes the EEG signal to have lower approximate entropy. The method discussed here can be applied and investigated in case of patients with brain diseases as the rehabilitation purpose.

  15. Multi-signal sedimentation velocity analysis with mass conservation for determining the stoichiometry of protein complexes.

    Directory of Open Access Journals (Sweden)

    Chad A Brautigam

    Full Text Available Multi-signal sedimentation velocity analytical ultracentrifugation (MSSV is a powerful tool for the determination of the number, stoichiometry, and hydrodynamic shape of reversible protein complexes in two- and three-component systems. In this method, the evolution of sedimentation profiles of macromolecular mixtures is recorded simultaneously using multiple absorbance and refractive index signals and globally transformed into both spectrally and diffusion-deconvoluted component sedimentation coefficient distributions. For reactions with complex lifetimes comparable to the time-scale of sedimentation, MSSV reveals the number and stoichiometry of co-existing complexes. For systems with short complex lifetimes, MSSV reveals the composition of the reaction boundary of the coupled reaction/migration process, which we show here may be used to directly determine an association constant. A prerequisite for MSSV is that the interacting components are spectrally distinguishable, which may be a result, for example, of extrinsic chromophores or of different abundances of aromatic amino acids contributing to the UV absorbance. For interacting components that are spectrally poorly resolved, here we introduce a method for additional regularization of the spectral deconvolution by exploiting approximate knowledge of the total loading concentrations. While this novel mass conservation principle does not discriminate contributions to different species, it can be effectively combined with constraints in the sedimentation coefficient range of uncomplexed species. We show in theory, computer simulations, and experiment, how mass conservation MSSV as implemented in SEDPHAT can enhance or even substitute for the spectral discrimination of components. This should broaden the applicability of MSSV to the analysis of the composition of reversible macromolecular complexes.

  16. The mediator complex in genomic and non-genomic signaling in cancer.

    Science.gov (United States)

    Weber, Hannah; Garabedian, Michael J

    2018-05-01

    Mediator is a conserved, multi-subunit macromolecular machine divided structurally into head, middle, and tail modules, along with a transiently associating kinase module. Mediator functions as an integrator of transcriptional regulatory activity by interacting with DNA-bound transcription factors and with RNA polymerase II (Pol II) to both activate and repress gene expression. Mediator has been shown to affect multiple steps in transcription, including chromatin looping between enhancers and promoters, pre-initiation complex formation, transcriptional elongation, and mRNA splicing. Individual Mediator subunits participate in regulation of gene expression by the estrogen and androgen receptors and are altered in a number of endocrine cancers, including breast and prostate cancer. In addition to its role in genomic signaling, MED12 has been implicated in non-genomic signaling by interacting with and activating TGF-beta receptor 2 in the cytoplasm. Recent structural studies have revealed extensive inter-domain interactions and complex architecture of the Mediator-Pol II complex, suggesting that Mediator is capable of reorganizing its conformation and composition to fit cellular needs. We propose that alterations in Mediator subunit expression that occur in various cancers could impact the organization and function of Mediator, resulting in changes in gene expression that promote malignancy. A better understanding of the role of Mediator in cancer could reveal new approaches to the diagnosis and treatment of Mediator-dependent endocrine cancers, especially in settings of therapy resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Jasmonate signalling in Arabidopsis involves SGT1b-HSP70-HSP90 chaperone complexes.

    Science.gov (United States)

    Zhang, Xue-Cheng; Millet, Yves A; Cheng, Zhenyu; Bush, Jenifer; Ausubel, Frederick M

    Plant hormones play pivotal roles in growth, development and stress responses. Although it is essential to our understanding of hormone signalling, how plants maintain a steady state level of hormone receptors is poorly understood. We show that mutation of the Arabidopsis thaliana co-chaperone SGT1b impairs responses to the plant hormones jasmonate, auxin and gibberellic acid, but not brassinolide and abscisic acid, and that SGT1b and its homologue SGT1a are involved in maintaining the steady state levels of the F-box proteins COI1 and TIR1, receptors for jasmonate and auxin, respectively. The association of SGT1b with COI1 is direct and is independent of the Arabidopsis SKP1 protein, ASK1. We further show that COI1 is a client protein of SGT1b-HSP70-HSP90 chaperone complexes and that the complexes function in hormone signalling by stabilizing the COI1 protein. This study extends the SGT1b-HSP90 client protein list and broadens the functional scope of SGT1b-HSP70-HSP90 chaperone complexes.

  18. Volterra representation enables modeling of complex synaptic nonlinear dynamics in large-scale simulations.

    Science.gov (United States)

    Hu, Eric Y; Bouteiller, Jean-Marie C; Song, Dong; Baudry, Michel; Berger, Theodore W

    2015-01-01

    Chemical synapses are comprised of a wide collection of intricate signaling pathways involving complex dynamics. These mechanisms are often reduced to simple spikes or exponential representations in order to enable computer simulations at higher spatial levels of complexity. However, these representations cannot capture important nonlinear dynamics found in synaptic transmission. Here, we propose an input-output (IO) synapse model capable of generating complex nonlinear dynamics while maintaining low computational complexity. This IO synapse model is an extension of a detailed mechanistic glutamatergic synapse model capable of capturing the input-output relationships of the mechanistic model using the Volterra functional power series. We demonstrate that the IO synapse model is able to successfully track the nonlinear dynamics of the synapse up to the third order with high accuracy. We also evaluate the accuracy of the IO synapse model at different input frequencies and compared its performance with that of kinetic models in compartmental neuron models. Our results demonstrate that the IO synapse model is capable of efficiently replicating complex nonlinear dynamics that were represented in the original mechanistic model and provide a method to replicate complex and diverse synaptic transmission within neuron network simulations.

  19. A complex symbol signal-to-noise ratio estimator and its performance

    Science.gov (United States)

    Feria, Y.

    1994-01-01

    This article presents an algorithm for estimating the signal-to-noise ratio (SNR) of signals that contain data on a downconverted suppressed carrier or the first harmonic of a square-wave subcarrier. This algorithm can be used to determine the performance of the full-spectrum combiner for the Galileo S-band (2.2- to 2.3-GHz) mission by measuring the input and output symbol SNR. A performance analysis of the algorithm shows that the estimator can estimate the complex symbol SNR using 10,000 symbols at a true symbol SNR of -5 dB with a mean of -4.9985 dB and a standard deviation of 0.2454 dB, and these analytical results are checked by simulations of 100 runs with a mean of -5.06 dB and a standard deviation of 0.2506 dB.

  20. Dynamic characteristics of two-state lasing quantum dot lasers under large signal modulation

    International Nuclear Information System (INIS)

    Lv, Zun-Ren; Ji, Hai-Ming; Luo, Shuai; Gao, Feng; Xu, Feng; Yang, Tao; Xiao, De-Hang

    2015-01-01

    Large signal modulation characteristics of the simultaneous ground-state (GS) and excited-state (ES) lasing quantum dot lasers are theoretically investigated. Relaxation oscillations of ‘0 → 1’ and ‘1 → 0’ in the GS lasing region (Region I), the transition region from GS lasing to two-state lasing (Region II) and the two-state lasing region (Region III) are compared and analyzed. It is found that the overshooting power and settling time in both Regions I and III decrease as the bias current increases. However, there exist abnormal behaviors of the overshooting power and settling time in Region II owing to the occurrence of ES lasing, which lead to fuzzy eye diagrams of the GS and ES lasing. Moreover, the ES lasing in Region III possesses much better eye diagrams because of its shorter settling time and smaller overshooting power over the GS lasing in Region I

  1. EIRP Characterization of Electrically Large Wireless Equipment with Integrated Signal Generator in a Compact Environment

    Directory of Open Access Journals (Sweden)

    Soon-Soo Oh

    2015-01-01

    Full Text Available We describe a measurement technique to characterize the equivalent isotropically radiated power (EIRP of electrically large wireless equipment in a compact environment. A modified phase-measurement method was proposed and, thus, the separation of the signal generator and radiating element was not required during the measurement. A Fresnel-to-far-field transformation was used for the fast measurement time in a compact anechoic chamber. An experimental verification of the method was carried out in a compact anechoic chamber, where the source-detector separation was approximately 1/5 of the far-field distance. The measured magnitude and phase pattern exhibited only a small error. The EIRP obtained using a Fresnel-to-far-field transformation was compared with a reference value, and the error was within 0.5 dB.

  2. Complex researches on substantiation of construction and seismic stability of large dams in seismic region

    International Nuclear Information System (INIS)

    Negmatullaev, S.Kh.; Yasunov, P.A.

    2001-01-01

    This article is devoted to complex researches on substantiation of construction and seismic stability of large dams (Nurec hydroelectric power station) in seismic region. Geological, seismological, model, and engineering investigations are discussed in this work. At construction of Nurec hydroelectric power station the rich experience is accumulated. This experience can be used in analogous seismically active regions at construction similar hydroelectric power stations.

  3. Defining Execution Viewpoints for a Large and Complex Software-Intensive System

    NARCIS (Netherlands)

    Callo Arias, Trosky B.; America, Pierre; Avgeriou, Paris

    2009-01-01

    An execution view is an important asset for developing large and complex systems. An execution view helps practitioners to describe, analyze, and communicate what a software system does at runtime and how it does it. In this paper, we present an approach to define execution viewpoints for an

  4. Par@Graph - a parallel toolbox for the construction and analysis of large complex climate networks

    NARCIS (Netherlands)

    Tantet, A.J.J.

    2015-01-01

    In this paper, we present Par@Graph, a software toolbox to reconstruct and analyze complex climate networks having a large number of nodes (up to at least 106) and edges (up to at least 1012). The key innovation is an efficient set of parallel software tools designed to leverage the inherited hybrid

  5. Software quality assurance: in large scale and complex software-intensive systems

    NARCIS (Netherlands)

    Mistrik, I.; Soley, R.; Ali, N.; Grundy, J.; Tekinerdogan, B.

    2015-01-01

    Software Quality Assurance in Large Scale and Complex Software-intensive Systems presents novel and high-quality research related approaches that relate the quality of software architecture to system requirements, system architecture and enterprise-architecture, or software testing. Modern software

  6. The magnetic g-tensors for ion complexes with large spin-orbit coupling

    International Nuclear Information System (INIS)

    Chang, P.K.L.; Liu, Y.S.

    1977-01-01

    A nonperturbative method for calculating the magnetic g-tensors is presented and discussed for complexes of transition metal ions of large spin-orbit coupling, in the ground term 2 D. A numerical example for CuCl 2 .2H 2 O is given [pt

  7. An Improved Conceptually-Based Method for Analysis of Communication Network Structure of Large Complex Organizations.

    Science.gov (United States)

    Richards, William D., Jr.

    Previous methods for determining the communication structure of organizations work well for small or simple organizations, but are either inadequate or unwieldy for use with large complex organizations. An improved method uses a number of different measures and a series of successive approximations to order the communication matrix such that…

  8. Valid knowledge for the professional design of large and complex design processes

    NARCIS (Netherlands)

    Aken, van J.E.

    2004-01-01

    The organization and planning of design processes, which we may regard as design process design, is an important issue. Especially for large and complex design-processes traditional approaches to process design may no longer suffice. The design literature gives quite some design process models. As

  9. Neurite, a finite difference large scale parallel program for the simulation of electrical signal propagation in neurites under mechanical loading.

    Directory of Open Access Journals (Sweden)

    Julián A García-Grajales

    Full Text Available With the growing body of research on traumatic brain injury and spinal cord injury, computational neuroscience has recently focused its modeling efforts on neuronal functional deficits following mechanical loading. However, in most of these efforts, cell damage is generally only characterized by purely mechanistic criteria, functions of quantities such as stress, strain or their corresponding rates. The modeling of functional deficits in neurites as a consequence of macroscopic mechanical insults has been rarely explored. In particular, a quantitative mechanically based model of electrophysiological impairment in neuronal cells, Neurite, has only very recently been proposed. In this paper, we present the implementation details of this model: a finite difference parallel program for simulating electrical signal propagation along neurites under mechanical loading. Following the application of a macroscopic strain at a given strain rate produced by a mechanical insult, Neurite is able to simulate the resulting neuronal electrical signal propagation, and thus the corresponding functional deficits. The simulation of the coupled mechanical and electrophysiological behaviors requires computational expensive calculations that increase in complexity as the network of the simulated cells grows. The solvers implemented in Neurite--explicit and implicit--were therefore parallelized using graphics processing units in order to reduce the burden of the simulation costs of large scale scenarios. Cable Theory and Hodgkin-Huxley models were implemented to account for the electrophysiological passive and active regions of a neurite, respectively, whereas a coupled mechanical model accounting for the neurite mechanical behavior within its surrounding medium was adopted as a link between electrophysiology and mechanics. This paper provides the details of the parallel implementation of Neurite, along with three different application examples: a long myelinated axon

  10. Max-Min SINR in Large-Scale Single-Cell MU-MIMO: Asymptotic Analysis and Low Complexity Transceivers

    KAUST Repository

    Sifaou, Houssem

    2016-12-28

    This work focuses on the downlink and uplink of large-scale single-cell MU-MIMO systems in which the base station (BS) endowed with M antennas communicates with K single-antenna user equipments (UEs). Particularly, we aim at reducing the complexity of the linear precoder and receiver that maximize the minimum signal-to-interference-plus-noise ratio subject to a given power constraint. To this end, we consider the asymptotic regime in which M and K grow large with a given ratio. Tools from random matrix theory (RMT) are then used to compute, in closed form, accurate approximations for the parameters of the optimal precoder and receiver, when imperfect channel state information (modeled by the generic Gauss-Markov formulation form) is available at the BS. The asymptotic analysis allows us to derive the asymptotically optimal linear precoder and receiver that are characterized by a lower complexity (due to the dependence on the large scale components of the channel) and, possibly, by a better resilience to imperfect channel state information. However, the implementation of both is still challenging as it requires fast inversions of large matrices in every coherence period. To overcome this issue, we apply the truncated polynomial expansion (TPE) technique to the precoding and receiving vector of each UE and make use of RMT to determine the optimal weighting coefficients on a per- UE basis that asymptotically solve the max-min SINR problem. Numerical results are used to validate the asymptotic analysis in the finite system regime and to show that the proposed TPE transceivers efficiently mimic the optimal ones, while requiring much lower computational complexity.

  11. Phase dynamics of complex-valued neural networks and its application to traffic signal control.

    Science.gov (United States)

    Nishikawa, Ikuko; Iritani, Takeshi; Sakakibara, Kazutoshi; Kuroe, Yasuaki

    2005-01-01

    Complex-valued Hopfield networks which possess the energy function are analyzed. The dynamics of the network with certain forms of an activation function is de-composable into the dynamics of the amplitude and phase of each neuron. Then the phase dynamics is described as a coupled system of phase oscillators with a pair-wise sinusoidal interaction. Therefore its phase synchronization mechanism is useful for the area-wide offset control of the traffic signals. The computer simulations show the effectiveness under the various traffic conditions.

  12. Measuring gas-residence times in large municipal incinerators, by means of a pseudo-random binary signal tracer technique

    International Nuclear Information System (INIS)

    Nasserzadeh, V.; Swithenbank, J.; Jones, B.

    1995-01-01

    The problem of measuring gas-residence time in large incinerators was studied by the pseudo-random binary sequence (PRBS) stimulus tracer response technique at the Sheffield municipal solid-waste incinerator (35 MW plant). The steady-state system was disturbed by the superimposition of small fluctuations in the form of a pseudo-random binary sequence of methane pulses, and the response of the incinerator was determined from the CO 2 concentration in flue gases at the boiler exit, measured with a specially developed optical gas analyser with a high-frequency response. For data acquisition, an on-line PC computer was used together with the LAB Windows software system; the output response was then cross-correlated with the perturbation signal to give the impulse response of the incinerator. There was very good agreement between the gas-residence time for the Sheffield MSW incinerator as calculated by computational fluid dynamics (FLUENT Model) and gas-residence time at the plant as measured by the PRBS tracer technique. The results obtained from this research programme clearly demonstrate that the PRBS stimulus tracer response technique can be successfully and economically used to measure gas-residence times in large incinerator plants. It also suggests that the common commercial practice of characterising the incinerator operation by a single-residence-time parameter may lead to a misrepresentation of the complexities involved in describing the operation of the incineration system. (author)

  13. LEGO-NMR spectroscopy: a method to visualize individual subunits in large heteromeric complexes.

    Science.gov (United States)

    Mund, Markus; Overbeck, Jan H; Ullmann, Janina; Sprangers, Remco

    2013-10-18

    Seeing the big picture: Asymmetric macromolecular complexes that are NMR active in only a subset of their subunits can be prepared, thus decreasing NMR spectral complexity. For the hetero heptameric LSm1-7 and LSm2-8 rings NMR spectra of the individual subunits of the complete complex are obtained, showing a conserved RNA binding site. This LEGO-NMR technique makes large asymmetric complexes accessible to detailed NMR spectroscopic studies. © 2013 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of Creative Commons the Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

  14. Generating functional analysis of complex formation and dissociation in large protein interaction networks

    International Nuclear Information System (INIS)

    Coolen, A C C; Rabello, S

    2009-01-01

    We analyze large systems of interacting proteins, using techniques from the non-equilibrium statistical mechanics of disordered many-particle systems. Apart from protein production and removal, the most relevant microscopic processes in the proteome are complex formation and dissociation, and the microscopic degrees of freedom are the evolving concentrations of unbound proteins (in multiple post-translational states) and of protein complexes. Here we only include dimer-complexes, for mathematical simplicity, and we draw the network that describes which proteins are reaction partners from an ensemble of random graphs with an arbitrary degree distribution. We show how generating functional analysis methods can be used successfully to derive closed equations for dynamical order parameters, representing an exact macroscopic description of the complex formation and dissociation dynamics in the infinite system limit. We end this paper with a discussion of the possible routes towards solving the nontrivial order parameter equations, either exactly (in specific limits) or approximately.

  15. Reionization on large scales. IV. Predictions for the 21 cm signal incorporating the light cone effect

    Energy Technology Data Exchange (ETDEWEB)

    La Plante, P.; Battaglia, N.; Natarajan, A.; Peterson, J. B.; Trac, H. [McWilliams Center for Cosmology, Department of Physics, Carnegie Mellon University, Pittsburgh, PA 15213 (United States); Cen, R. [Department of Astrophysical Science, Princeton University, Princeton, NJ 08544 (United States); Loeb, A., E-mail: plaplant@andrew.cmu.edu [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States)

    2014-07-01

    We present predictions for the 21 cm brightness temperature power spectrum during the Epoch of Reionization (EoR). We discuss the implications of the 'light cone' effect, which incorporates evolution of the neutral hydrogen fraction and 21 cm brightness temperature along the line of sight. Using a novel method calibrated against radiation-hydrodynamic simulations, we model the neutral hydrogen density field and 21 cm signal in large volumes (L = 2 Gpc h {sup –1}). The inclusion of the light cone effect leads to a relative decrease of about 50% in the 21 cm power spectrum on all scales. We also find that the effect is more prominent at the midpoint of reionization and later. The light cone effect can also introduce an anisotropy along the line of sight. By decomposing the 3D power spectrum into components perpendicular to and along the line of sight, we find that in our fiducial reionization model, there is no significant anisotropy. However, parallel modes can contribute up to 40% more power for shorter reionization scenarios. The scales on which the light cone effect is relevant are comparable to scales where one measures the baryon acoustic oscillation. We argue that due to its large comoving scale and introduction of anisotropy, the light cone effect is important when considering redshift space distortions and future application to the Alcock-Paczyński test for the determination of cosmological parameters.

  16. Application of «Sensor signal analysis network» complex for distributed, time synchronized analysis of electromagnetic radiation

    Science.gov (United States)

    Mochalov, Vladimir; Mochalova, Anastasia

    2017-10-01

    The paper considers a developing software-hardware complex «Sensor signal analysis network» for distributed and time synchronized analysis of electromagnetic radiations. The areas of application and the main features of the complex are described. An example of application of the complex to monitor natural electromagnetic radiation sources is considered based on the data recorded in VLF range. A generalized functional scheme of stream analysis of signals by a complex functional node is suggested and its application for stream detection of atmospherics, whistlers and tweaks is considered.

  17. Hierarchical modeling and robust synthesis for the preliminary design of large scale complex systems

    Science.gov (United States)

    Koch, Patrick Nathan

    Large-scale complex systems are characterized by multiple interacting subsystems and the analysis of multiple disciplines. The design and development of such systems inevitably requires the resolution of multiple conflicting objectives. The size of complex systems, however, prohibits the development of comprehensive system models, and thus these systems must be partitioned into their constituent parts. Because simultaneous solution of individual subsystem models is often not manageable iteration is inevitable and often excessive. In this dissertation these issues are addressed through the development of a method for hierarchical robust preliminary design exploration to facilitate concurrent system and subsystem design exploration, for the concurrent generation of robust system and subsystem specifications for the preliminary design of multi-level, multi-objective, large-scale complex systems. This method is developed through the integration and expansion of current design techniques: (1) Hierarchical partitioning and modeling techniques for partitioning large-scale complex systems into more tractable parts, and allowing integration of subproblems for system synthesis, (2) Statistical experimentation and approximation techniques for increasing both the efficiency and the comprehensiveness of preliminary design exploration, and (3) Noise modeling techniques for implementing robust preliminary design when approximate models are employed. The method developed and associated approaches are illustrated through their application to the preliminary design of a commercial turbofan turbine propulsion system; the turbofan system-level problem is partitioned into engine cycle and configuration design and a compressor module is integrated for more detailed subsystem-level design exploration, improving system evaluation.

  18. Design Implementation and Testing of a VLSI High Performance ASIC for Extracting the Phase of a Complex Signal

    National Research Council Canada - National Science Library

    Altmeyer, Ronald

    2002-01-01

    This thesis documents the research, circuit design, and simulation testing of a VLSI ASIC which extracts phase angle information from a complex sampled signal using the arctangent relationship: (phi=tan/-1 (Q/1...

  19. Value of spatial planning for large mining and energy complexes. [Yugoslavia

    Energy Technology Data Exchange (ETDEWEB)

    Matko, Z; Spasic, N

    1982-01-01

    In the example of the Kosovo complex (Socialist Federated Republic of Yugoslovia) an examination is made of the value of developing a spatial plan for the territory of large mining-energy complexes. The goals and expected results of spatial planning are discussed. The open method of working lignite, fuel shale and other fossil energy raw material fields at the modern level of development of technology, in addition to large-volume physical interferences in space, causes considerable structural changes of functional-economic, socioeconomic and psychological-sociological nature in the direct zone of influence of the mining-energy complex. Improvement in technology of working a lignite field does not guarantee in the near future any solutions in developing the mining-energy complexes, and therefore it is necessary to count on considerable volume of degradation of space which is governed by the existing technology. Under these conditions detailed planning and regulation of space is especially important, if one views them as a component part of long term policy for development of the mining energy complex and the zones of its influence.

  20. Predicting the performance of a power amplifier using large-signal circuit simulations of an AlGaN/GaN HFET model

    Science.gov (United States)

    Bilbro, Griff L.; Hou, Danqiong; Yin, Hong; Trew, Robert J.

    2009-02-01

    We have quantitatively modeled the conduction current and charge storage of an HFET in terms its physical dimensions and material properties. For DC or small-signal RF operation, no adjustable parameters are necessary to predict the terminal characteristics of the device. Linear performance measures such as small-signal gain and input admittance can be predicted directly from the geometric structure and material properties assumed for the device design. We have validated our model at low-frequency against experimental I-V measurements and against two-dimensional device simulations. We discuss our recent extension of our model to include a larger class of electron velocity-field curves. We also discuss the recent reformulation of our model to facilitate its implementation in commercial large-signal high-frequency circuit simulators. Large signal RF operation is more complex. First, the highest CW microwave power is fundamentally bounded by a brief, reversible channel breakdown in each RF cycle. Second, the highest experimental measurements of efficiency, power, or linearity always require harmonic load pull and possibly also harmonic source pull. Presently, our model accounts for these facts with an adjustable breakdown voltage and with adjustable load impedances and source impedances for the fundamental frequency and its harmonics. This has allowed us to validate our model for large signal RF conditions by simultaneously fitting experimental measurements of output power, gain, and power added efficiency of real devices. We show that the resulting model can be used to compare alternative device designs in terms of their large signal performance, such as their output power at 1dB gain compression or their third order intercept points. In addition, the model provides insight into new device physics features enabled by the unprecedented current and voltage levels of AlGaN/GaN HFETs, including non-ohmic resistance in the source access regions and partial depletion of

  1. Influence of the large-small split effect on strategy choice in complex subtraction.

    Science.gov (United States)

    Xiang, Yan Hui; Wu, Hao; Shang, Rui Hong; Chao, Xiaomei; Ren, Ting Ting; Zheng, Li Ling; Mo, Lei

    2018-04-01

    Two main theories have been used to explain the arithmetic split effect: decision-making process theory and strategy choice theory. Using the inequality paradigm, previous studies have confirmed that individuals tend to adopt a plausibility-checking strategy and a whole-calculation strategy to solve large and small split problems in complex addition arithmetic, respectively. This supports strategy choice theory, but it is unknown whether this theory also explains performance in solving different split problems in complex subtraction arithmetic. This study used small, intermediate and large split sizes, with each split condition being further divided into problems requiring and not requiring borrowing. The reaction times (RTs) for large and intermediate splits were significantly shorter than those for small splits, while accuracy was significantly higher for large and middle splits than for small splits, reflecting no speed-accuracy trade-off. Further, RTs and accuracy differed significantly between the borrow and no-borrow conditions only for small splits. This study indicates that strategy choice theory is suitable to explain the split effect in complex subtraction arithmetic. That is, individuals tend to choose the plausibility-checking strategy or the whole-calculation strategy according to the split size. © 2016 International Union of Psychological Science.

  2. How Project Managers Really Manage: An Indepth Look at Some Managers of Large, Complex NASA Projects

    Science.gov (United States)

    Mulenburg, Gerald M.; Impaeilla, Cliff (Technical Monitor)

    2000-01-01

    This paper reports on a research study by the author that examined ten contemporary National Aeronautics and Space Administration (NASA) complex projects. In-depth interviews with the project managers of these projects provided qualitative data about the inner workings of the project and the methodologies used in establishing and managing the projects. The inclusion of a variety of space, aeronautics, and ground based projects from several different NASA research centers helped to reduce potential bias in the findings toward any one type of project, or technical discipline. The findings address the participants and their individual approaches. The discussion includes possible implications for project managers of other large, complex, projects.

  3. Systems Perturbation Analysis of a Large-Scale Signal Transduction Model Reveals Potentially Influential Candidates for Cancer Therapeutics

    Science.gov (United States)

    Puniya, Bhanwar Lal; Allen, Laura; Hochfelder, Colleen; Majumder, Mahbubul; Helikar, Tomáš

    2016-01-01

    Dysregulation in signal transduction pathways can lead to a variety of complex disorders, including cancer. Computational approaches such as network analysis are important tools to understand system dynamics as well as to identify critical components that could be further explored as therapeutic targets. Here, we performed perturbation analysis of a large-scale signal transduction model in extracellular environments that stimulate cell death, growth, motility, and quiescence. Each of the model’s components was perturbed under both loss-of-function and gain-of-function mutations. Using 1,300 simulations under both types of perturbations across various extracellular conditions, we identified the most and least influential components based on the magnitude of their influence on the rest of the system. Based on the premise that the most influential components might serve as better drug targets, we characterized them for biological functions, housekeeping genes, essential genes, and druggable proteins. The most influential components under all environmental conditions were enriched with several biological processes. The inositol pathway was found as most influential under inactivating perturbations, whereas the kinase and small lung cancer pathways were identified as the most influential under activating perturbations. The most influential components were enriched with essential genes and druggable proteins. Moreover, known cancer drug targets were also classified in influential components based on the affected components in the network. Additionally, the systemic perturbation analysis of the model revealed a network motif of most influential components which affect each other. Furthermore, our analysis predicted novel combinations of cancer drug targets with various effects on other most influential components. We found that the combinatorial perturbation consisting of PI3K inactivation and overactivation of IP3R1 can lead to increased activity levels of apoptosis

  4. Improving seasonal forecasts of hydroclimatic variables through the state of multiple large-scale climate signals

    Science.gov (United States)

    Castelletti, A.; Giuliani, M.; Block, P. J.

    2017-12-01

    Increasingly uncertain hydrologic regimes combined with more frequent and intense extreme events are challenging water systems management worldwide, emphasizing the need of accurate medium- to long-term predictions to timely prompt anticipatory operations. Despite modern forecasts are skillful over short lead time (from hours to days), predictability generally tends to decrease on longer lead times. Global climate teleconnection, such as El Niño Southern Oscillation (ENSO), may contribute in extending forecast lead times. However, ENSO teleconnection is well defined in some locations, such as Western USA and Australia, while there is no consensus on how it can be detected and used in other regions, particularly in Europe, Africa, and Asia. In this work, we generalize the Niño Index Phase Analysis (NIPA) framework by contributing the Multi Variate Niño Index Phase Analysis (MV-NIPA), which allows capturing the state of multiple large-scale climate signals (i.e. ENSO, North Atlantic Oscillation, Pacific Decadal Oscillation, Atlantic Multi-decadal Oscillation, Indian Ocean Dipole) to forecast hydroclimatic variables on a seasonal time scale. Specifically, our approach distinguishes the different phases of the considered climate signals and, for each phase, identifies relevant anomalies in Sea Surface Temperature (SST) that influence the local hydrologic conditions. The potential of the MV-NIPA framework is demonstrated through an application to the Lake Como system, a regulated lake in northern Italy which is mainly operated for flood control and irrigation supply. Numerical results show high correlations between seasonal SST values and one season-ahead precipitation in the Lake Como basin. The skill of the resulting MV-NIPA forecast outperforms the one of ECMWF products. This information represents a valuable contribution to partially anticipate the summer water availability, especially during drought events, ultimately supporting the improvement of the Lake Como

  5. Generation of Long-time Complex Signals for Testing the Instruments for Detection of Voltage Quality Disturbances

    Science.gov (United States)

    Živanović, Dragan; Simić, Milan; Kokolanski, Zivko; Denić, Dragan; Dimcev, Vladimir

    2018-04-01

    Software supported procedure for generation of long-time complex test sentences, suitable for testing the instruments for detection of standard voltage quality (VQ) disturbances is presented in this paper. This solution for test signal generation includes significant improvements of computer-based signal generator presented and described in the previously published paper [1]. The generator is based on virtual instrumentation software for defining the basic signal parameters, data acquisition card NI 6343, and power amplifier for amplification of output voltage level to the nominal RMS voltage value of 230 V. Definition of basic signal parameters in LabVIEW application software is supported using Script files, which allows simple repetition of specific test signals and combination of more different test sequences in the complex composite test waveform. The basic advantage of this generator compared to the similar solutions for signal generation is the possibility for long-time test sequence generation according to predefined complex test scenarios, including various combinations of VQ disturbances defined in accordance with the European standard EN50160. Experimental verification of the presented signal generator capability is performed by testing the commercial power quality analyzer Fluke 435 Series II. In this paper are shown some characteristic complex test signals with various disturbances and logged data obtained from the tested power quality analyzer.

  6. JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

    Science.gov (United States)

    Zeke, András; Misheva, Mariya

    2016-01-01

    SUMMARY The c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states. PMID:27466283

  7. Complex mineralization at large ore deposits in the Russian Far East

    Science.gov (United States)

    Schneider, A. A.; Malyshev, Yu. F.; Goroshko, M. V.; Romanovsky, N. P.

    2011-04-01

    Genetic and mineralogical features of large deposits with complex Sn, W, and Mo mineralization in the Sikhote-Alin and Amur-Khingan metallogenic provinces are considered, as well as those of raremetal, rare earth, and uranium deposits in the Aldan-Stanovoi province. The spatiotemporal, geological, and mineralogical attributes of large deposits are set forth, and their geodynamic settings are determined. These attributes are exemplified in the large Tigriny Sn-W greisen-type deposit. The variation of regional tectonic settings and their spatial superposition are the main factor controlling formation of large deposits. Such a variation gives rise to multiple reactivation of the ore-magmatic system and long-term, multistage formation of deposits. Pulsatory mineralogical zoning with telescoped mineral assemblages related to different stages results in the formation of complex ores. The highest-grade zones of mass discharge of hydrothermal solutions are formed at the deposits. The promising greisen-type mineralization with complex Sn-W-Mo ore is suggested to be an additional source of tungsten and molybdenum. The Tigriny, Pravourminsky, and Arsen'evsky deposits, as well as deposits of the Komsomol'sk and Khingan-Olonoi ore districts are examples. Large and superlarge U, Ta, Nb, Be, and REE deposits are localized in the southeastern Aldan-Stanovoi Shield. The Ulkan and Arbarastakh ore districts attract special attention. The confirmed prospects of new large deposits with Sn, W, Mo, Ta, Nb, Be, REE, and U mineralization in the south of the Russian Far East assure expediency of further geological exploration in this territory.

  8. Binding of Signal Recognition Particle Gives Ribosome/Nascent Chain Complexes a Competitive Advantage in Endoplasmic Reticulum Membrane Interaction

    Science.gov (United States)

    Neuhof, Andrea; Rolls, Melissa M.; Jungnickel, Berit; Kalies, Kai-Uwe; Rapoport, Tom A.

    1998-01-01

    Most secretory and membrane proteins are sorted by signal sequences to the endoplasmic reticulum (ER) membrane early during their synthesis. Targeting of the ribosome-nascent chain complex (RNC) involves the binding of the signal sequence to the signal recognition particle (SRP), followed by an interaction of ribosome-bound SRP with the SRP receptor. However, ribosomes can also independently bind to the ER translocation channel formed by the Sec61p complex. To explain the specificity of membrane targeting, it has therefore been proposed that nascent polypeptide-associated complex functions as a cytosolic inhibitor of signal sequence- and SRP-independent ribosome binding to the ER membrane. We report here that SRP-independent binding of RNCs to the ER membrane can occur in the presence of all cytosolic factors, including nascent polypeptide-associated complex. Nontranslating ribosomes competitively inhibit SRP-independent membrane binding of RNCs but have no effect when SRP is bound to the RNCs. The protective effect of SRP against ribosome competition depends on a functional signal sequence in the nascent chain and is also observed with reconstituted proteoliposomes containing only the Sec61p complex and the SRP receptor. We conclude that cytosolic factors do not prevent the membrane binding of ribosomes. Instead, specific ribosome targeting to the Sec61p complex is provided by the binding of SRP to RNCs, followed by an interaction with the SRP receptor, which gives RNC–SRP complexes a selective advantage in membrane targeting over nontranslating ribosomes. PMID:9436994

  9. Importance of Mediator complex in the regulation and integration of diverse signaling pathways in plants

    Directory of Open Access Journals (Sweden)

    Subhasis eSamanta

    2015-09-01

    Full Text Available Basic transcriptional machinery in eukaryotes is assisted by a number of cofactors, which either increase or decrease the rate of transcription. Mediator complex is one such cofactor, and recently has drawn a lot of interest because of its integrative power to converge different signaling pathways before channelling the transcription instructions to the RNA polymerase II machinery. Like yeast and metazoans, plants do possess the Mediator complex across the kingdom, and its isolation and subunit analyses have been reported from the model plant, Arabidopsis. Genetic and molecular analyses have unravelled important regulatory roles of Mediator subunits at every stage of plant life cycle starting from flowering to embryo and organ development, to even size determination. It also contributes immensely to the survival of plants against different environmental vagaries by the timely activation of its resistance mechanisms. Here, we have provided an overview of plant Mediator complex starting from its discovery to regulation of stoichiometry of its subunits. We have also reviewed involvement of different Mediator subunits in different processes and pathways including defense response pathways evoked by diverse biotic cues. Wherever possible, attempts have been made to provide mechanistic insight of Mediator’s involvement in these processes.

  10. Importance of Mediator complex in the regulation and integration of diverse signaling pathways in plants.

    Science.gov (United States)

    Samanta, Subhasis; Thakur, Jitendra K

    2015-01-01

    Basic transcriptional machinery in eukaryotes is assisted by a number of cofactors, which either increase or decrease the rate of transcription. Mediator complex is one such cofactor, and recently has drawn a lot of interest because of its integrative power to converge different signaling pathways before channeling the transcription instructions to the RNA polymerase II machinery. Like yeast and metazoans, plants do possess the Mediator complex across the kingdom, and its isolation and subunit analyses have been reported from the model plant, Arabidopsis. Genetic, and molecular analyses have unraveled important regulatory roles of Mediator subunits at every stage of plant life cycle starting from flowering to embryo and organ development, to even size determination. It also contributes immensely to the survival of plants against different environmental vagaries by the timely activation of its resistance mechanisms. Here, we have provided an overview of plant Mediator complex starting from its discovery to regulation of stoichiometry of its subunits. We have also reviewed involvement of different Mediator subunits in different processes and pathways including defense response pathways evoked by diverse biotic cues. Wherever possible, attempts have been made to provide mechanistic insight of Mediator's involvement in these processes.

  11. Methods Dealing with Complexity in Selecting Joint Venture Contractors for Large-Scale Infrastructure Projects

    Directory of Open Access Journals (Sweden)

    Ru Liang

    2018-01-01

    Full Text Available The magnitude of business dynamics has increased rapidly due to increased complexity, uncertainty, and risk of large-scale infrastructure projects. This fact made it increasingly tough to “go alone” into a contractor. As a consequence, joint venture contractors with diverse strengths and weaknesses cooperatively bid for bidding. Understanding project complexity and making decision on the optimal joint venture contractor is challenging. This paper is to study how to select joint venture contractors for undertaking large-scale infrastructure projects based on a multiattribute mathematical model. Two different methods are developed to solve the problem. One is based on ideal points and the other one is based on balanced ideal advantages. Both of the two methods consider individual difference in expert judgment and contractor attributes. A case study of Hong Kong-Zhuhai-Macao-Bridge (HZMB project in China is used to demonstrate how to apply these two methods and their advantages.

  12. Studies on combined model based on functional objectives of large scale complex engineering

    Science.gov (United States)

    Yuting, Wang; Jingchun, Feng; Jiabao, Sun

    2018-03-01

    As various functions were included in large scale complex engineering, and each function would be conducted with completion of one or more projects, combined projects affecting their functions should be located. Based on the types of project portfolio, the relationship of projects and their functional objectives were analyzed. On that premise, portfolio projects-technics based on their functional objectives were introduced, then we studied and raised the principles of portfolio projects-technics based on the functional objectives of projects. In addition, The processes of combined projects were also constructed. With the help of portfolio projects-technics based on the functional objectives of projects, our research findings laid a good foundation for management of large scale complex engineering portfolio management.

  13. Demonstration and comparison of tuned and detuned signal recycling in a large-scale gravitational wave detector

    International Nuclear Information System (INIS)

    Hild, S; Grote, H; Hewtison, M; Lueck, H; Smith, J R; Strain, K A; Willke, B; Danzmann, K

    2007-01-01

    The British/German gravitational wave detector GEO 600 located near Hannover in Germany is the first large-scale gravitational-wave detector using the advanced technique of signal recycling. Currently the instrument operates in detuned signal recycling mode. Several problems arise due to the fact that the signal recycling cavity changes amplitude and phase of all light fields (carrier and sidebands) present at the dark-port. In addition, in the case of detuned signal recycling this leads to unbalanced sideband fields at the detector output. The large amplitude modulation caused by this asymmetry does not carry any gravitational wave information, but might be the cause of saturation and nonlinearities on the main photodiode. We developed and demonstrated a new control method to realize tuned signal recycling operation in a large-scale gravitational wave detector. A detailed comparison of tuned and detuned signal recycling operation is given. The response function of the system (optical gain) was measured and compared, as was the size of amplitude modulation on the main photodiode. Some important noise couplings were measured and partly found to be strongly reduced in the case of tuned signal recycling operation

  14. Research on a Small Signal Stability Region Boundary Model of the Interconnected Power System with Large-Scale Wind Power

    Directory of Open Access Journals (Sweden)

    Wenying Liu

    2015-03-01

    Full Text Available For the interconnected power system with large-scale wind power, the problem of the small signal stability has become the bottleneck of restricting the sending-out of wind power as well as the security and stability of the whole power system. Around this issue, this paper establishes a small signal stability region boundary model of the interconnected power system with large-scale wind power based on catastrophe theory, providing a new method for analyzing the small signal stability. Firstly, we analyzed the typical characteristics and the mathematic model of the interconnected power system with wind power and pointed out that conventional methods can’t directly identify the topological properties of small signal stability region boundaries. For this problem, adopting catastrophe theory, we established a small signal stability region boundary model of the interconnected power system with large-scale wind power in two-dimensional power injection space and extended it to multiple dimensions to obtain the boundary model in multidimensional power injection space. Thirdly, we analyzed qualitatively the topological property’s changes of the small signal stability region boundary caused by large-scale wind power integration. Finally, we built simulation models by DIgSILENT/PowerFactory software and the final simulation results verified the correctness and effectiveness of the proposed model.

  15. Does reef architectural complexity influence resource availability for a large reef-dwelling invertebrate?

    Science.gov (United States)

    Lozano-Álvarez, Enrique; Luviano-Aparicio, Nelia; Negrete-Soto, Fernando; Barradas-Ortiz, Cecilia; Aguíñiga-García, Sergio; Morillo-Velarde, Piedad S.; Álvarez-Filip, Lorenzo; Briones-Fourzán, Patricia

    2017-10-01

    In coral reefs, loss of architectural complexity and its associated habitat degradation is expected to affect reef specialists in particular due to changes in resource availability. We explored whether these features could potentially affect populations of a large invertebrate, the spotted spiny lobster Panulirus guttatus, which is an obligate Caribbean coral reef-dweller with a limited home range. We selected two separate large coral reef patches in Puerto Morelos (Mexico) that differed significantly in structural complexity and level of degradation, as assessed via the rugosity index, habitat assessment score, and percent cover of various benthic components. On each reef, we estimated density of P. guttatus and sampled lobsters to analyze their stomach contents, three different condition indices, and stable isotopes (δ15N and δ13C) in muscle. Lobster density did not vary with reef, suggesting that available crevices in the less complex patch still provided adequate refuge to these lobsters. Lobsters consumed many food types, dominated by mollusks and crustaceans, but proportionally more crustaceans (herbivore crabs) in the less complex patch, which had more calcareous macroalgae and algal turf. Lobsters from both reefs had a similar condition (all three indices) and mean δ15N, suggesting a similar quality of diet between reefs related to their opportunistic feeding, but differed in mean δ13C values, reflecting the different carbon sources between reefs and providing indirect evidence of individuals of P. guttatus foraging exclusively over their home reef. Overall, we found no apparent effects of architectural complexity, at least to the degree observed in our less complex patch, on density, condition, or trophic level of P. guttatus.

  16. Universal properties of type IIB and F-theory flux compactifications at large complex structure

    International Nuclear Information System (INIS)

    Marsh, M.C. David; Sousa, Kepa

    2016-01-01

    We consider flux compactifications of type IIB string theory and F-theory in which the respective superpotentials at large complex structure are dominated by cubic or quartic terms in the complex structure moduli. In this limit, the low-energy effective theory exhibits universal properties that are insensitive to the details of the compactification manifold or the flux configuration. Focussing on the complex structure and axio-dilaton sector, we show that there are no vacua in this region and the spectrum of the Hessian matrix is highly peaked and consists only of three distinct eigenvalues (0, 2m 3/2 2 and 8m 3/2 2 ), independently of the number of moduli. We briefly comment on how the inclusion of Kähler moduli affect these findings. Our results generalise those of Brodie & Marsh http://dx.doi.org/10.1007/JHEP01(2016)037, in which these universal properties were found in a subspace of the large complex structure limit of type IIB compactifications.

  17. Pilot Study of Topical Copper Chlorophyllin Complex in Subjects With Facial Acne and Large Pores.

    Science.gov (United States)

    Stephens, Thomas J; McCook, John P; Herndon, James H

    2015-06-01

    Acne vulgaris is one of the most common skin diseases treated by dermatologists. Salts of copper chlorophyllin complex are semi-synthetic naturally-derived compounds with antioxidant, anti-inflammatory and wound healing activity that have not been previously tested topically in the treatment of acne-prone skin with enlarged pores. This single-center pilot study was conducted to assess the efficacy and safety of a liposomal dispersion of topically applied sodium copper chlorophyllin complex in subjects with mild-moderate acne and large, visible pores over a course of 3 weeks. Subjects were supplied with the test product, a topical gel containing a liposomal dispersion of sodium copper chlorophyllin complex (0.1%) with directions to apply a small amount to the facial area twice daily. Clinical assessments were performed at screening/baseline and at week 3. VISIA readings were taken and self-assessment questionnaires were conducted. 10 subjects were enrolled and completed the 3-week study. All clinical efficacy parameters showed statistically significant improvements over baseline at week 3. The study product was well tolerated. Subject questionnaires showed the test product was highly rated. In this pilot study, a topical formulation containing a liposomal dispersion of sodium copper chlorophyllin complex was shown to be clinically effective and well tolerated for the treatment of mild-moderate acne and large, visible pores when used for 3 weeks.

  18. The spectra of type IIB flux compactifications at large complex structure

    International Nuclear Information System (INIS)

    Brodie, Callum; Marsh, M.C. David

    2016-01-01

    We compute the spectra of the Hessian matrix, H, and the matrix M that governs the critical point equation of the low-energy effective supergravity, as a function of the complex structure and axio-dilaton moduli space in type IIB flux compactifications at large complex structure. We find both spectra analytically in an h − 1,2 +3 real-dimensional subspace of the moduli space, and show that they exhibit a universal structure with highly degenerate eigenvalues, independently of the choice of flux, the details of the compactification geometry, and the number of complex structure moduli. In this subspace, the spectrum of the Hessian matrix contains no tachyons, but there are also no critical points. We show numerically that the spectra of H and M remain highly peaked over a large fraction of the sampled moduli space of explicit Calabi-Yau compactifications with 2 to 5 complex structure moduli. In these models, the scale of the supersymmetric contribution to the scalar masses is strongly linearly correlated with the value of the superpotential over almost the entire moduli space, with particularly strong correlations arising for g s <1. We contrast these results with the expectations from the much-used continuous flux approximation, and comment on the applicability of Random Matrix Theory to the statistical modelling of the string theory landscape.

  19. Cell–cell signaling drives the evolution of complex traits: introduction—lung evo-devo

    Science.gov (United States)

    Torday, John S.; Rehan, V. K.

    2009-01-01

    Physiology integrates biology with the environment through cell–cell interactions at multiple levels. The evolution of the respiratory system has been “deconvoluted” (Torday and Rehan in Am J Respir Cell Mol Biol 31:8–12, 2004) through Gene Regulatory Networks (GRNs) applied to cell–cell communication for all aspects of lung biology development, homeostasis, regeneration, and aging. Using this approach, we have predicted the phenotypic consequences of failed signaling for lung development, homeostasis, and regeneration based on evolutionary principles. This cell–cell communication model predicts other aspects of vertebrate physiology as adaptational responses. For example, the oxygen-induced differentiation of alveolar myocytes into alveolar adipocytes was critical for the evolution of the lung in land dwelling animals adapting to fluctuating Phanarezoic oxygen levels over the past 500 million years. Adipocytes prevent lung injury due to oxygen radicals and facilitate the rise of endothermy. In addition, they produce the class I cytokine leptin, which augments pulmonary surfactant activity and alveolar surface area, increasing selection pressure for both respiratory oxygenation and metabolic demand initially constrained by high-systemic vascular pressure, but subsequently compensated by the evolution of the adrenomedullary beta-adrenergic receptor mechanism. Conserted positive selection for the lung and adrenals created further selection pressure for the heart, which becomes progressively more complex phylogenetically in tandem with the lung. Developmentally, increasing heart complexity and size impinges precociously on the gut mesoderm to induce the liver. That evolutionary-developmental interaction is significant because the liver provides regulated sources of glucose and glycogen to the evolving physiologic system, which is necessary for the evolution of the neocortex. Evolution of neocortical control furthers integration of physiologic systems. Such

  20. The Hrs/Stam complex acts as a positive and negative regulator of RTK signaling during Drosophila development.

    Directory of Open Access Journals (Sweden)

    Hélène Chanut-Delalande

    Full Text Available BACKGROUND: Endocytosis is a key regulatory step of diverse signalling pathways, including receptor tyrosine kinase (RTK signalling. Hrs and Stam constitute the ESCRT-0 complex that controls the initial selection of ubiquitinated proteins, which will subsequently be degraded in lysosomes. It has been well established ex vivo and during Drosophila embryogenesis that Hrs promotes EGFR down regulation. We have recently isolated the first mutations of stam in flies and shown that Stam is required for air sac morphogenesis, a larval respiratory structure whose formation critically depends on finely tuned levels of FGFR activity. This suggest that Stam, putatively within the ESCRT-0 complex, modulates FGF signalling, a possibility that has not been examined in Drosophila yet. PRINCIPAL FINDINGS: Here, we assessed the role of the Hrs/Stam complex in the regulation of signalling activity during Drosophila development. We show that stam and hrs are required for efficient FGFR signalling in the tracheal system, both during cell migration in the air sac primordium and during the formation of fine cytoplasmic extensions in terminal cells. We find that stam and hrs mutant cells display altered FGFR/Btl localisation, likely contributing to impaired signalling levels. Electron microscopy analyses indicate that endosome maturation is impaired at distinct steps by hrs and stam mutations. These somewhat unexpected results prompted us to further explore the function of stam and hrs in EGFR signalling. We show that while stam and hrs together downregulate EGFR signalling in the embryo, they are required for full activation of EGFR signalling during wing development. CONCLUSIONS/SIGNIFICANCE: Our study shows that the ESCRT-0 complex differentially regulates RTK signalling, either positively or negatively depending on tissues and developmental stages, further highlighting the importance of endocytosis in modulating signalling pathways during development.

  1. Parameter and State Estimation of Large-Scale Complex Systems Using Python Tools

    Directory of Open Access Journals (Sweden)

    M. Anushka S. Perera

    2015-07-01

    Full Text Available This paper discusses the topics related to automating parameter, disturbance and state estimation analysis of large-scale complex nonlinear dynamic systems using free programming tools. For large-scale complex systems, before implementing any state estimator, the system should be analyzed for structural observability and the structural observability analysis can be automated using Modelica and Python. As a result of structural observability analysis, the system may be decomposed into subsystems where some of them may be observable --- with respect to parameter, disturbances, and states --- while some may not. The state estimation process is carried out for those observable subsystems and the optimum number of additional measurements are prescribed for unobservable subsystems to make them observable. In this paper, an industrial case study is considered: the copper production process at Glencore Nikkelverk, Kristiansand, Norway. The copper production process is a large-scale complex system. It is shown how to implement various state estimators, in Python, to estimate parameters and disturbances, in addition to states, based on available measurements.

  2. Orientation Encoding and Viewpoint Invariance in Face Recognition: Inferring Neural Properties from Large-Scale Signals.

    Science.gov (United States)

    Ramírez, Fernando M

    2018-05-01

    Viewpoint-invariant face recognition is thought to be subserved by a distributed network of occipitotemporal face-selective areas that, except for the human anterior temporal lobe, have been shown to also contain face-orientation information. This review begins by highlighting the importance of bilateral symmetry for viewpoint-invariant recognition and face-orientation perception. Then, monkey electrophysiological evidence is surveyed describing key tuning properties of face-selective neurons-including neurons bimodally tuned to mirror-symmetric face-views-followed by studies combining functional magnetic resonance imaging (fMRI) and multivariate pattern analyses to probe the representation of face-orientation and identity information in humans. Altogether, neuroimaging studies suggest that face-identity is gradually disentangled from face-orientation information along the ventral visual processing stream. The evidence seems to diverge, however, regarding the prevalent form of tuning of neural populations in human face-selective areas. In this context, caveats possibly leading to erroneous inferences regarding mirror-symmetric coding are exposed, including the need to distinguish angular from Euclidean distances when interpreting multivariate pattern analyses. On this basis, this review argues that evidence from the fusiform face area is best explained by a view-sensitive code reflecting head angular disparity, consistent with a role of this area in face-orientation perception. Finally, the importance is stressed of explicit models relating neural properties to large-scale signals.

  3. Statistical Modeling of Large-Scale Signal Path Loss in Underwater Acoustic Networks

    Directory of Open Access Journals (Sweden)

    Manuel Perez Malumbres

    2013-02-01

    Full Text Available In an underwater acoustic channel, the propagation conditions are known to vary in time, causing the deviation of the received signal strength from the nominal value predicted by a deterministic propagation model. To facilitate a large-scale system design in such conditions (e.g., power allocation, we have developed a statistical propagation model in which the transmission loss is treated as a random variable. By applying repetitive computation to the acoustic field, using ray tracing for a set of varying environmental conditions (surface height, wave activity, small node displacements around nominal locations, etc., an ensemble of transmission losses is compiled and later used to infer the statistical model parameters. A reasonable agreement is found with log-normal distribution, whose mean obeys a log-distance increases, and whose variance appears to be constant for a certain range of inter-node distances in a given deployment location. The statistical model is deemed useful for higher-level system planning, where simulation is needed to assess the performance of candidate network protocols under various resource allocation policies, i.e., to determine the transmit power and bandwidth allocation necessary to achieve a desired level of performance (connectivity, throughput, reliability, etc..

  4. Fractional Modeling of the AC Large-Signal Frequency Response in Magnetoresistive Current Sensors

    Directory of Open Access Journals (Sweden)

    Sergio Iván Ravelo Arias

    2013-12-01

    Full Text Available Fractional calculus is considered when derivatives and integrals of non-integer order are applied over a specific function. In the electrical and electronic domain, the transfer function dependence of a fractional filter not only by the filter order n, but additionally, of the fractional order α is an example of a great number of systems where its input-output behavior could be more exactly modeled by a fractional behavior. Following this aim, the present work shows the experimental ac large-signal frequency response of a family of electrical current sensors based in different spintronic conduction mechanisms. Using an ac characterization set-up the sensor transimpedance function  is obtained considering it as the relationship between sensor output voltage and input sensing current,[PLEASE CHECK FORMULA IN THE PDF]. The study has been extended to various magnetoresistance sensors based in different technologies like anisotropic magnetoresistance (AMR, giant magnetoresistance (GMR, spin-valve (GMR-SV and tunnel magnetoresistance (TMR. The resulting modeling shows two predominant behaviors, the low-pass and the inverse low-pass with fractional index different from the classical integer response. The TMR technology with internal magnetization offers the best dynamic and sensitivity properties opening the way to develop actual industrial applications.

  5. Large signal-to-noise ratio quantification in MLE for ARARMAX models

    Science.gov (United States)

    Zou, Yiqun; Tang, Xiafei

    2014-06-01

    It has been shown that closed-loop linear system identification by indirect method can be generally transferred to open-loop ARARMAX (AutoRegressive AutoRegressive Moving Average with eXogenous input) estimation. For such models, the gradient-related optimisation with large enough signal-to-noise ratio (SNR) can avoid the potential local convergence in maximum likelihood estimation. To ease the application of this condition, the threshold SNR needs to be quantified. In this paper, we build the amplitude coefficient which is an equivalence to the SNR and prove the finiteness of the threshold amplitude coefficient within the stability region. The quantification of threshold is achieved by the minimisation of an elaborately designed multi-variable cost function which unifies all the restrictions on the amplitude coefficient. The corresponding algorithm based on two sets of physically realisable system input-output data details the minimisation and also points out how to use the gradient-related method to estimate ARARMAX parameters when local minimum is present as the SNR is small. Then, the algorithm is tested on a theoretical AutoRegressive Moving Average with eXogenous input model for the derivation of the threshold and a gas turbine engine real system for model identification, respectively. Finally, the graphical validation of threshold on a two-dimensional plot is discussed.

  6. Etoile Project : Social Intelligent ICT-System for very large scale education in complex systems

    Science.gov (United States)

    Bourgine, P.; Johnson, J.

    2009-04-01

    The project will devise new theory and implement new ICT-based methods of delivering high-quality low-cost postgraduate education to many thousands of people in a scalable way, with the cost of each extra student being negligible (Socially Intelligent Resource Mining system to gather large volumes of high quality educational resources from the internet; new methods to deconstruct these to produce a semantically tagged Learning Object Database; a Living Course Ecology to support the creation and maintenance of evolving course materials; systems to deliver courses; and a ‘socially intelligent assessment system'. The system will be tested on one to ten thousand postgraduate students in Europe working towards the Complex System Society's title of European PhD in Complex Systems. Étoile will have a very high impact both scientifically and socially by (i) the provision of new scalable ICT-based methods for providing very low cost scientific education, (ii) the creation of new mathematical and statistical theory for the multiscale dynamics of complex systems, (iii) the provision of a working example of adaptation and emergence in complex socio-technical systems, and (iv) making a major educational contribution to European complex systems science and its applications.

  7. Survey of large protein complexes D. vulgaris reveals great structural diversity

    Energy Technology Data Exchange (ETDEWEB)

    Han, B.-G.; Dong, M.; Liu, H.; Camp, L.; Geller, J.; Singer, M.; Hazen, T. C.; Choi, M.; Witkowska, H. E.; Ball, D. A.; Typke, D.; Downing, K. H.; Shatsky, M.; Brenner, S. E.; Chandonia, J.-M.; Biggin, M. D.; Glaeser, R. M.

    2009-08-15

    An unbiased survey has been made of the stable, most abundant multi-protein complexes in Desulfovibrio vulgaris Hildenborough (DvH) that are larger than Mr {approx} 400 k. The quaternary structures for 8 of the 16 complexes purified during this work were determined by single-particle reconstruction of negatively stained specimens, a success rate {approx}10 times greater than that of previous 'proteomic' screens. In addition, the subunit compositions and stoichiometries of the remaining complexes were determined by biochemical methods. Our data show that the structures of only two of these large complexes, out of the 13 in this set that have recognizable functions, can be modeled with confidence based on the structures of known homologs. These results indicate that there is significantly greater variability in the way that homologous prokaryotic macromolecular complexes are assembled than has generally been appreciated. As a consequence, we suggest that relying solely on previously determined quaternary structures for homologous proteins may not be sufficient to properly understand their role in another cell of interest.

  8. Iterative methods for the solution of very large complex symmetric linear systems of equations in electrodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Clemens, M.; Weiland, T. [Technische Hochschule Darmstadt (Germany)

    1996-12-31

    In the field of computational electrodynamics the discretization of Maxwell`s equations using the Finite Integration Theory (FIT) yields very large, sparse, complex symmetric linear systems of equations. For this class of complex non-Hermitian systems a number of conjugate gradient-type algorithms is considered. The complex version of the biconjugate gradient (BiCG) method by Jacobs can be extended to a whole class of methods for complex-symmetric algorithms SCBiCG(T, n), which only require one matrix vector multiplication per iteration step. In this class the well-known conjugate orthogonal conjugate gradient (COCG) method for complex-symmetric systems corresponds to the case n = 0. The case n = 1 yields the BiCGCR method which corresponds to the conjugate residual algorithm for the real-valued case. These methods in combination with a minimal residual smoothing process are applied separately to practical 3D electro-quasistatical and eddy-current problems in electrodynamics. The practical performance of the SCBiCG methods is compared with other methods such as QMR and TFQMR.

  9. Employing the Hilbert-Huang Transform to analyze observed natural complex signals: Calm wind meandering cases

    Science.gov (United States)

    Martins, Luis Gustavo Nogueira; Stefanello, Michel Baptistella; Degrazia, Gervásio Annes; Acevedo, Otávio Costa; Puhales, Franciano Scremin; Demarco, Giuliano; Mortarini, Luca; Anfossi, Domenico; Roberti, Débora Regina; Costa, Felipe Denardin; Maldaner, Silvana

    2016-11-01

    In this study we analyze natural complex signals employing the Hilbert-Huang spectral analysis. Specifically, low wind meandering meteorological data are decomposed into turbulent and non turbulent components. These non turbulent movements, responsible for the absence of a preferential direction of the horizontal wind, provoke negative lobes in the meandering autocorrelation functions. The meandering characteristic time scales (meandering periods) are determined from the spectral peak provided by the Hilbert-Huang marginal spectrum. The magnitudes of the temperature and horizontal wind meandering period obtained agree with the results found from the best fit of the heuristic meandering autocorrelation functions. Therefore, the new method represents a new procedure to evaluate meandering periods that does not employ mathematical expressions to represent observed meandering autocorrelation functions.

  10. Ant Queen Egg-Marking Signals: Matching Deceptive Laboratory Simplicity with Natural Complexity

    DEFF Research Database (Denmark)

    van Zweden, Jelle Stijn; Heinze, Jürgen; Boomsma, Jacobus Jan

    2009-01-01

    Background Experiments under controlled laboratory conditions can produce decisive evidence for testing biological hypotheses, provided they are representative of the more complex natural conditions. However, whether this requirement is fulfilled is seldom tested explicitly. Here we provide a lab....../field comparison to investigate the identity of an egg-marking signal of ant queens. Our study was based on ant workers resolving conflict over male production by destroying each other's eggs, but leaving queen eggs unharmed. For this, the workers need a proximate cue to discriminate between the two egg types...... that this compound by itself is not the natural queen egg-marking pheromone. We subsequently investigated the overall differences of entire chemical profiles of eggs, and found that queen-laid eggs in field colonies are more distinct from worker-laid eggs than in lab colonies, have more variation in profiles...

  11. Low-complexity camera digital signal imaging for video document projection system

    Science.gov (United States)

    Hsia, Shih-Chang; Tsai, Po-Shien

    2011-04-01

    We present high-performance and low-complexity algorithms for real-time camera imaging applications. The main functions of the proposed camera digital signal processing (DSP) involve color interpolation, white balance, adaptive binary processing, auto gain control, and edge and color enhancement for video projection systems. A series of simulations demonstrate that the proposed method can achieve good image quality while keeping computation cost and memory requirements low. On the basis of the proposed algorithms, the cost-effective hardware core is developed using Verilog HDL. The prototype chip has been verified with one low-cost programmable device. The real-time camera system can achieve 1270 × 792 resolution with the combination of extra components and can demonstrate each DSP function.

  12. Optimal sensor configuration for complex systems with application to signal detection in structures

    DEFF Research Database (Denmark)

    Sadegh, Payman; Spall, J. C.

    2000-01-01

    sensor outputs. Secondly, we describe an efficient and practical algorithm to achieve the optimization goals, based on simultaneous perturbation stochastic approximation (SPSA). SPSA avoids the need for detailed modeling of the sensor response by simply relying on observed responses as obtained......The paper considers the problem of sensor configuration for complex systems. The contribution of the paper is twofold. Firstly, we define an appropriate criterion that is based on maximizing overall sensor responses while minimizing redundant information as measured by correlations between multiple...... by limited experimentation with test sensor configurations. We illustrate the application of the approach to optimal placement of acoustic sensors for signal detection in structures. This includes both a computer simulation study for an aluminum plate, and real experimentations on a steel I-beam....

  13. CD25 and CD69 induction by α4β1 outside-in signalling requires TCR early signalling complex proteins

    Science.gov (United States)

    Cimo, Ann-Marie; Ahmed, Zamal; McIntyre, Bradley W.; Lewis, Dorothy E.; Ladbury, John E.

    2013-01-01

    Distinct signalling pathways producing diverse cellular outcomes can utilize similar subsets of proteins. For example, proteins from the TCR (T-cell receptor) ESC (early signalling complex) are also involved in interferon-α receptor signalling. Defining the mechanism for how these proteins function within a given pathway is important in understanding the integration and communication of signalling networks with one another. We investigated the contributions of the TCR ESC proteins Lck (lymphocyte-specific kinase), ZAP-70 (ζ-chain-associated protein of 70 kDa), Vav1, SLP-76 [SH2 (Src homology 2)-domain-containing leukocyte protein of 76 kDa] and LAT (linker for activation of T-cells) to integrin outside-in signalling in human T-cells. Lck, ZAP-70, SLP-76, Vav1 and LAT were activated by α4β1 outside-in signalling, but in a manner different from TCR signalling. TCR stimulation recruits ESC proteins to activate the mitogen-activated protein kinase ERK (extracellular-signal-regulated kinase). α4β1 outside-in-mediated ERK activation did not require TCR ESC proteins. However, α4β1 outside-in signalling induced CD25 and co-stimulated CD69 and this was dependent on TCR ESC proteins. TCR and α4β1 outside-in signalling are integrated through the common use of TCR ESC proteins; however, these proteins display functionally distinct roles in these pathways. These novel insights into the cross-talk between integrin outside-in and TCR signalling pathways are highly relevant to the development of therapeutic strategies to overcome disease associated with T-cell deregulation. PMID:23758320

  14. Interdependence of free zinc changes and protein complex assembly - insights into zinc signal regulation.

    Science.gov (United States)

    Kocyła, Anna; Adamczyk, Justyna; Krężel, Artur

    2018-01-24

    Cellular zinc (Zn(ii)) is bound with proteins that are part of the proteomes of all domains of life. It is mostly utilized as a catalytic or structural protein cofactor, which results in a vast number of binding architectures. The Zn(ii) ion is also important for the formation of transient protein complexes with a Zn(ii)-dependent quaternary structure that is formed upon cellular zinc signals. The mechanisms by which proteins associate with and dissociate from Zn(ii) and the connection with cellular Zn(ii) changes remain incompletely understood. In this study, we aimed to examine how zinc protein domains with various Zn(ii)-binding architectures are formed under free Zn(ii) concentration changes and how formation of the Zn(ii)-dependent assemblies is related to the protein concentration and reactivity. To accomplish these goals we chose four zinc domains with different Zn(ii)-to-protein binding stoichiometries: classical zinc finger (ZnP), LIM domain (Zn 2 P), zinc hook (ZnP 2 ) and zinc clasp (ZnP 1 P 2 ) folds. Our research demonstrated a lack of changes in the saturation level of intraprotein zinc binding sites, despite various peptide concentrations, while homo- and heterodimers indicated a concentration-dependent tendency. In other words, at a certain free Zn(ii) concentration, the fraction of a formed dimeric complex increases or decreases with subunit concentration changes. Secondly, even small or local changes in free Zn(ii) may significantly affect protein saturation depending on its architecture, function and subcellular concentration. In our paper, we indicate the importance of interdependence of free Zn(ii) availability and protein subunit concentrations for cellular zinc signal regulation.

  15. Complex singularities of the critical potential in the large-N limit

    International Nuclear Information System (INIS)

    Meurice, Y.

    2003-01-01

    We show with two numerical examples that the conventional expansion in powers of the field for the critical potential of 3-dimensional O(N) models in the large-N limit does not converge for values of φ 2 larger than some critical value. This can be explained by the existence of conjugated branch points in the complex φ 2 plane. Pade approximants [L+3/L] for the critical potential apparently converge at large φ 2 . This allows high-precision calculation of the fixed point in a more suitable set of coordinates. We argue that the singularities are generic and not an artifact of the large-N limit. We show that ignoring these singularities may lead to inaccurate approximations

  16. Micro-earthquake signal analysis and hypocenter determination around Lokon volcano complex

    Energy Technology Data Exchange (ETDEWEB)

    Firmansyah, Rizky, E-mail: rizkyfirmansyah@hotmail.com [Geophysical Engineering, Faculty of Mining and Petroleum Engineering, Institut Teknologi Bandung, Bandung, 40132 (Indonesia); Nugraha, Andri Dian, E-mail: nugraha@gf.itb.ac.id [Global Geophysical Group, Faculty of Mining and Petroleum Engineering, Institut Teknologi Bandung, Bandung, 40132 (Indonesia); Kristianto, E-mail: kris@vsi.esdm.go.id [Center for Volcanology and Geological Hazard Mitigation (CVGHM), Geological Agency, Bandung, 40122 (Indonesia)

    2015-04-24

    Mount Lokon is one of five active volcanoes which is located in the North Sulawesi region. Since June 26{sup th}, 2011, standby alert set by the Center for Volcanology and Geological Hazard Mitigation (CVGHM) for this mountain. The Mount Lokon volcano erupted on July 4{sup th}, 2011 and still continuously erupted until August 28{sup th}, 2011. Due to its high seismic activity, this study is focused to analysis of micro-earthquake signal and determine the micro-earthquake hypocenter location around the complex area of Lokon-Empung Volcano before eruption phase in 2011 (time periods of January, 2009 up to March, 2010). Determination of the hypocenter location was conducted with Geiger Adaptive Damping (GAD) method. We used initial model from previous study in Volcan de Colima, Mexico. The reason behind the model selection was based on the same characteristics that shared between Mount Lokon and Colima including andesitic stratovolcano and small-plinian explosions volcanian types. In this study, a picking events was limited to the volcano-tectonics of A and B types, hybrid, long-period that has a clear signal onset, and local tectonic with different maximum S – P time are not more than three seconds. As a result, we observed the micro-earthquakes occurred in the area north-west of Mount Lokon region.

  17. Micro-earthquake signal analysis and hypocenter determination around Lokon volcano complex

    International Nuclear Information System (INIS)

    Firmansyah, Rizky; Nugraha, Andri Dian; Kristianto

    2015-01-01

    Mount Lokon is one of five active volcanoes which is located in the North Sulawesi region. Since June 26 th , 2011, standby alert set by the Center for Volcanology and Geological Hazard Mitigation (CVGHM) for this mountain. The Mount Lokon volcano erupted on July 4 th , 2011 and still continuously erupted until August 28 th , 2011. Due to its high seismic activity, this study is focused to analysis of micro-earthquake signal and determine the micro-earthquake hypocenter location around the complex area of Lokon-Empung Volcano before eruption phase in 2011 (time periods of January, 2009 up to March, 2010). Determination of the hypocenter location was conducted with Geiger Adaptive Damping (GAD) method. We used initial model from previous study in Volcan de Colima, Mexico. The reason behind the model selection was based on the same characteristics that shared between Mount Lokon and Colima including andesitic stratovolcano and small-plinian explosions volcanian types. In this study, a picking events was limited to the volcano-tectonics of A and B types, hybrid, long-period that has a clear signal onset, and local tectonic with different maximum S – P time are not more than three seconds. As a result, we observed the micro-earthquakes occurred in the area north-west of Mount Lokon region

  18. Large system change challenges: addressing complex critical issues in linked physical and social domains

    Science.gov (United States)

    Waddell, Steve; Cornell, Sarah; Hsueh, Joe; Ozer, Ceren; McLachlan, Milla; Birney, Anna

    2015-04-01

    Most action to address contemporary complex challenges, including the urgent issues of global sustainability, occurs piecemeal and without meaningful guidance from leading complex change knowledge and methods. The potential benefit of using such knowledge is greater efficacy of effort and investment. However, this knowledge and its associated tools and methods are under-utilized because understanding about them is low, fragmented between diverse knowledge traditions, and often requires shifts in mindsets and skills from expert-led to participant-based action. We have been engaged in diverse action-oriented research efforts in Large System Change for sustainability. For us, "large" systems can be characterized as large-scale systems - up to global - with many components, of many kinds (physical, biological, institutional, cultural/conceptual), operating at multiple levels, driven by multiple forces, and presenting major challenges for people involved. We see change of such systems as complex challenges, in contrast with simple or complicated problems, or chaotic situations. In other words, issues and sub-systems have unclear boundaries, interact with each other, and are often contradictory; dynamics are non-linear; issues are not "controllable", and "solutions" are "emergent" and often paradoxical. Since choices are opportunity-, power- and value-driven, these social, institutional and cultural factors need to be made explicit in any actionable theory of change. Our emerging network is sharing and building a knowledge base of experience, heuristics, and theories of change from multiple disciplines and practice domains. We will present our views on focal issues for the development of the field of large system change, which include processes of goal-setting and alignment; leverage of systemic transitions and transformation; and the role of choice in influencing critical change processes, when only some sub-systems or levels of the system behave in purposeful ways

  19. Efficient transmission of subthreshold signals in complex networks of spiking neurons.

    Science.gov (United States)

    Torres, Joaquin J; Elices, Irene; Marro, J

    2015-01-01

    We investigate the efficient transmission and processing of weak, subthreshold signals in a realistic neural medium in the presence of different levels of the underlying noise. Assuming Hebbian weights for maximal synaptic conductances--that naturally balances the network with excitatory and inhibitory synapses--and considering short-term synaptic plasticity affecting such conductances, we found different dynamic phases in the system. This includes a memory phase where population of neurons remain synchronized, an oscillatory phase where transitions between different synchronized populations of neurons appears and an asynchronous or noisy phase. When a weak stimulus input is applied to each neuron, increasing the level of noise in the medium we found an efficient transmission of such stimuli around the transition and critical points separating different phases for well-defined different levels of stochasticity in the system. We proved that this intriguing phenomenon is quite robust, as it occurs in different situations including several types of synaptic plasticity, different type and number of stored patterns and diverse network topologies, namely, diluted networks and complex topologies such as scale-free and small-world networks. We conclude that the robustness of the phenomenon in different realistic scenarios, including spiking neurons, short-term synaptic plasticity and complex networks topologies, make very likely that it could also occur in actual neural systems as recent psycho-physical experiments suggest.

  20. Efficient transmission of subthreshold signals in complex networks of spiking neurons.

    Directory of Open Access Journals (Sweden)

    Joaquin J Torres

    Full Text Available We investigate the efficient transmission and processing of weak, subthreshold signals in a realistic neural medium in the presence of different levels of the underlying noise. Assuming Hebbian weights for maximal synaptic conductances--that naturally balances the network with excitatory and inhibitory synapses--and considering short-term synaptic plasticity affecting such conductances, we found different dynamic phases in the system. This includes a memory phase where population of neurons remain synchronized, an oscillatory phase where transitions between different synchronized populations of neurons appears and an asynchronous or noisy phase. When a weak stimulus input is applied to each neuron, increasing the level of noise in the medium we found an efficient transmission of such stimuli around the transition and critical points separating different phases for well-defined different levels of stochasticity in the system. We proved that this intriguing phenomenon is quite robust, as it occurs in different situations including several types of synaptic plasticity, different type and number of stored patterns and diverse network topologies, namely, diluted networks and complex topologies such as scale-free and small-world networks. We conclude that the robustness of the phenomenon in different realistic scenarios, including spiking neurons, short-term synaptic plasticity and complex networks topologies, make very likely that it could also occur in actual neural systems as recent psycho-physical experiments suggest.

  1. Cadherin complexes recruit mRNAs and RISC to regulate epithelial cell signaling.

    Science.gov (United States)

    Kourtidis, Antonis; Necela, Brian; Lin, Wan-Hsin; Lu, Ruifeng; Feathers, Ryan W; Asmann, Yan W; Thompson, E Aubrey; Anastasiadis, Panos Z

    2017-10-02

    Cumulative evidence demonstrates that most RNAs exhibit specific subcellular distribution. However, the mechanisms regulating this phenomenon and its functional consequences are still under investigation. Here, we reveal that cadherin complexes at the apical zonula adherens (ZA) of epithelial adherens junctions recruit the core components of the RNA-induced silencing complex (RISC) Ago2, GW182, and PABPC1, as well as a set of 522 messenger RNAs (mRNAs) and 28 mature microRNAs (miRNAs or miRs), via PLEKHA7. Top canonical pathways represented by these mRNAs include Wnt/β-catenin, TGF-β, and stem cell signaling. We specifically demonstrate the presence and silencing of MYC, JUN, and SOX2 mRNAs by miR-24 and miR-200c at the ZA. PLEKHA7 knockdown dissociates RISC from the ZA, decreases loading of the ZA-associated mRNAs and miRNAs to Ago2, and results in a corresponding increase of MYC, JUN, and SOX2 protein expression. The present work reveals a mechanism that directly links junction integrity to the silencing of a set of mRNAs that critically affect epithelial homeostasis. © 2017 Kourtidis et al.

  2. A large scale analysis of information-theoretic network complexity measures using chemical structures.

    Directory of Open Access Journals (Sweden)

    Matthias Dehmer

    Full Text Available This paper aims to investigate information-theoretic network complexity measures which have already been intensely used in mathematical- and medicinal chemistry including drug design. Numerous such measures have been developed so far but many of them lack a meaningful interpretation, e.g., we want to examine which kind of structural information they detect. Therefore, our main contribution is to shed light on the relatedness between some selected information measures for graphs by performing a large scale analysis using chemical networks. Starting from several sets containing real and synthetic chemical structures represented by graphs, we study the relatedness between a classical (partition-based complexity measure called the topological information content of a graph and some others inferred by a different paradigm leading to partition-independent measures. Moreover, we evaluate the uniqueness of network complexity measures numerically. Generally, a high uniqueness is an important and desirable property when designing novel topological descriptors having the potential to be applied to large chemical databases.

  3. Final Report: Large-Scale Optimization for Bayesian Inference in Complex Systems

    Energy Technology Data Exchange (ETDEWEB)

    Ghattas, Omar [The University of Texas at Austin

    2013-10-15

    The SAGUARO (Scalable Algorithms for Groundwater Uncertainty Analysis and Robust Optimiza- tion) Project focuses on the development of scalable numerical algorithms for large-scale Bayesian inversion in complex systems that capitalize on advances in large-scale simulation-based optimiza- tion and inversion methods. Our research is directed in three complementary areas: efficient approximations of the Hessian operator, reductions in complexity of forward simulations via stochastic spectral approximations and model reduction, and employing large-scale optimization concepts to accelerate sampling. Our efforts are integrated in the context of a challenging testbed problem that considers subsurface reacting flow and transport. The MIT component of the SAGUARO Project addresses the intractability of conventional sampling methods for large-scale statistical inverse problems by devising reduced-order models that are faithful to the full-order model over a wide range of parameter values; sampling then employs the reduced model rather than the full model, resulting in very large computational savings. Results indicate little effect on the computed posterior distribution. On the other hand, in the Texas-Georgia Tech component of the project, we retain the full-order model, but exploit inverse problem structure (adjoint-based gradients and partial Hessian information of the parameter-to- observation map) to implicitly extract lower dimensional information on the posterior distribution; this greatly speeds up sampling methods, so that fewer sampling points are needed. We can think of these two approaches as "reduce then sample" and "sample then reduce." In fact, these two approaches are complementary, and can be used in conjunction with each other. Moreover, they both exploit deterministic inverse problem structure, in the form of adjoint-based gradient and Hessian information of the underlying parameter-to-observation map, to achieve their speedups.

  4. Sedimentation Velocity Analysis of Large Oligomeric Chromatin Complexes Using Interference Detection.

    Science.gov (United States)

    Rogge, Ryan A; Hansen, Jeffrey C

    2015-01-01

    Sedimentation velocity experiments measure the transport of molecules in solution under centrifugal force. Here, we describe a method for monitoring the sedimentation of very large biological molecular assemblies using the interference optical systems of the analytical ultracentrifuge. The mass, partial-specific volume, and shape of macromolecules in solution affect their sedimentation rates as reflected in the sedimentation coefficient. The sedimentation coefficient is obtained by measuring the solute concentration as a function of radial distance during centrifugation. Monitoring the concentration can be accomplished using interference optics, absorbance optics, or the fluorescence detection system, each with inherent advantages. The interference optical system captures data much faster than these other optical systems, allowing for sedimentation velocity analysis of extremely large macromolecular complexes that sediment rapidly at very low rotor speeds. Supramolecular oligomeric complexes produced by self-association of 12-mer chromatin fibers are used to illustrate the advantages of the interference optics. Using interference optics, we show that chromatin fibers self-associate at physiological divalent salt concentrations to form structures that sediment between 10,000 and 350,000S. The method for characterizing chromatin oligomers described in this chapter will be generally useful for characterization of any biological structures that are too large to be studied by the absorbance optical system. © 2015 Elsevier Inc. All rights reserved.

  5. Gcn4-Mediator Specificity Is Mediated by a Large and Dynamic Fuzzy Protein-Protein Complex

    Directory of Open Access Journals (Sweden)

    Lisa M. Tuttle

    2018-03-01

    Full Text Available Summary: Transcription activation domains (ADs are inherently disordered proteins that often target multiple coactivator complexes, but the specificity of these interactions is not understood. Efficient transcription activation by yeast Gcn4 requires its tandem ADs and four activator-binding domains (ABDs on its target, the Mediator subunit Med15. Multiple ABDs are a common feature of coactivator complexes. We find that the large Gcn4-Med15 complex is heterogeneous and contains nearly all possible AD-ABD interactions. Gcn4-Med15 forms via a dynamic fuzzy protein-protein interface, where ADs bind the ABDs in multiple orientations via hydrophobic regions that gain helicity. This combinatorial mechanism allows individual low-affinity and specificity interactions to generate a biologically functional, specific, and higher affinity complex despite lacking a defined protein-protein interface. This binding strategy is likely representative of many activators that target multiple coactivators, as it allows great flexibility in combinations of activators that can cooperate to regulate genes with variable coactivator requirements. : Tuttle et al. report a “fuzzy free-for-all” interaction mechanism that explains how seemingly unrelated transcription activators converge on a limited number of coactivator targets. The mechanism provides a rationale for the observation that individually weak and low-specificity interactions can combine to produce biologically critical function without requiring highly ordered structure. Keywords: transcription activation, intrinsically disordered proteins, fuzzy binding

  6. Large eddy simulation modeling of particle-laden flows in complex terrain

    Science.gov (United States)

    Salesky, S.; Giometto, M. G.; Chamecki, M.; Lehning, M.; Parlange, M. B.

    2017-12-01

    The transport, deposition, and erosion of heavy particles over complex terrain in the atmospheric boundary layer is an important process for hydrology, air quality forecasting, biology, and geomorphology. However, in situ observations can be challenging in complex terrain due to spatial heterogeneity. Furthermore, there is a need to develop numerical tools that can accurately represent the physics of these multiphase flows over complex surfaces. We present a new numerical approach to accurately model the transport and deposition of heavy particles in complex terrain using large eddy simulation (LES). Particle transport is represented through solution of the advection-diffusion equation including terms that represent gravitational settling and inertia. The particle conservation equation is discretized in a cut-cell finite volume framework in order to accurately enforce mass conservation. Simulation results will be validated with experimental data, and numerical considerations required to enforce boundary conditions at the surface will be discussed. Applications will be presented in the context of snow deposition and transport, as well as urban dispersion.

  7. Gcn4-Mediator Specificity Is Mediated by a Large and Dynamic Fuzzy Protein-Protein Complex.

    Science.gov (United States)

    Tuttle, Lisa M; Pacheco, Derek; Warfield, Linda; Luo, Jie; Ranish, Jeff; Hahn, Steven; Klevit, Rachel E

    2018-03-20

    Transcription activation domains (ADs) are inherently disordered proteins that often target multiple coactivator complexes, but the specificity of these interactions is not understood. Efficient transcription activation by yeast Gcn4 requires its tandem ADs and four activator-binding domains (ABDs) on its target, the Mediator subunit Med15. Multiple ABDs are a common feature of coactivator complexes. We find that the large Gcn4-Med15 complex is heterogeneous and contains nearly all possible AD-ABD interactions. Gcn4-Med15 forms via a dynamic fuzzy protein-protein interface, where ADs bind the ABDs in multiple orientations via hydrophobic regions that gain helicity. This combinatorial mechanism allows individual low-affinity and specificity interactions to generate a biologically functional, specific, and higher affinity complex despite lacking a defined protein-protein interface. This binding strategy is likely representative of many activators that target multiple coactivators, as it allows great flexibility in combinations of activators that can cooperate to regulate genes with variable coactivator requirements. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Axiomatic design in large systems complex products, buildings and manufacturing systems

    CERN Document Server

    Suh, Nam

    2016-01-01

    This book provides a synthesis of recent developments in Axiomatic Design theory and its application in large complex systems. Introductory chapters provide concise tutorial materials for graduate students and new practitioners, presenting the fundamentals of Axiomatic Design and relating its key concepts to those of model-based systems engineering. A mathematical exposition of design axioms is also provided. The main body of the book, which represents a concentrated treatment of several applications, is divided into three parts covering work on: complex products; buildings; and manufacturing systems. The book shows how design work in these areas can benefit from the scientific and systematic underpinning provided by Axiomatic Design, and in so doing effectively combines the state of the art in design research with practice. All contributions were written by an international group of leading proponents of Axiomatic Design. The book concludes with a call to action motivating further research into the engineeri...

  9. Engineering a large application software project: the controls of the CERN PS accelerator complex

    International Nuclear Information System (INIS)

    Benincasa, G.P.; Daneels, A.; Heymans, P.; Serre, Ch.

    1985-01-01

    The CERN PS accelerator complex has been progressively converted to full computer controls without interrupting its full-time operation (more than 6000 hours per year with on average not more than 1% of the total down-time due to controls). The application software amounts to 120 man-years and 450'000 instructions: it compares with other large software projects, also outside the accelerator world: e.g. Skylab's ground support software. This paper outlines the application software structure which takes into account technical requirements and constraints (resulting from the complexity of the process and its operation) and economical and managerial ones. It presents the engineering and management techniques used to promote implementation, testing and commissioning within budget, manpower and time constraints and concludes with experience gained

  10. Some thoughts on the management of large, complex international space ventures

    Science.gov (United States)

    Lee, T. J.; Kutzer, Ants; Schneider, W. C.

    1992-01-01

    Management issues relevant to the development and deployment of large international space ventures are discussed with particular attention given to previous experience. Management approaches utilized in the past are labeled as either simple or complex, and signs of efficient management are examined. Simple approaches include those in which experiments and subsystems are developed for integration into spacecraft, and the Apollo-Soyuz Test Project is given as an example of a simple multinational approach. Complex approaches include those for ESA's Spacelab Project and the Space Station Freedom in which functional interfaces cross agency and political boundaries. It is concluded that individual elements of space programs should be managed by individual participating agencies, and overall configuration control is coordinated by level with a program director acting to manage overall objectives and project interfaces.

  11. SPECTROSCOPIC STUDY OF THE N159/N160 COMPLEX IN THE LARGE MAGELLANIC CLOUD

    International Nuclear Information System (INIS)

    Farina, Cecilia; Bosch, Guillermo L.; Morrell, Nidia I.; Barba, Rodolfo H.; Walborn, Nolan R.

    2009-01-01

    We present a spectroscopic study of the N159/N160 massive star-forming region south of 30 Doradus in the Large Magellanic Cloud, classifying a total of 189 stars in the field of the complex. Most of them belong to O and early B spectral classes; we have also found some uncommon and very interesting spectra, including members of the Onfp class, a Be P Cygni star, and some possible multiple systems. Using spectral types as broad indicators of evolutionary stages, we considered the evolutionary status of the region as a whole. We infer that massive stars at different evolutionary stages are present throughout the region, favoring the idea of a common time for the origin of recent star formation in the N159/N160 complex as a whole, while sequential star formation at different rates is probably present in several subregions.

  12. Control protocol: large scale implementation at the CERN PS complex - a first assessment

    International Nuclear Information System (INIS)

    Abie, H.; Benincasa, G.; Coudert, G.; Davydenko, Y.; Dehavay, C.; Gavaggio, R.; Gelato, G.; Heinze, W.; Legras, M.; Lustig, H.; Merard, L.; Pearson, T.; Strubin, P.; Tedesco, J.

    1994-01-01

    The Control Protocol is a model-based, uniform access procedure from a control system to accelerator equipment. It was proposed at CERN about 5 years ago and prototypes were developed in the following years. More recently, this procedure has been finalized and implemented at a large scale in the PS Complex. More than 300 pieces of equipment are now using this protocol in normal operation and another 300 are under implementation. These include power converters, vacuum systems, beam instrumentation devices, RF equipment, etc. This paper describes how the single general procedure is applied to the different kinds of equipment. The advantages obtained are also discussed. ((orig.))

  13. Complex Security System for Premises Under Conditions of Large Volume of Passenger Traffic

    Directory of Open Access Journals (Sweden)

    Yakubov Vladimir

    2016-01-01

    Full Text Available Subsystems of the design of a complex security system for premises under conditions of large volume of passenger traffic are considered. These subsystems provide video- and thermal imaging control, radio wave tomography, and gas analysis. Simultaneous application of all examined variants will essentially increase the probability of timely prevention of dangerous situations with the probability of false alarm as low as possible. It is important that finally, this will provide protection of population and will facilitate the work of intelligence services.

  14. Descriptive Study of an Outbreak of Avian Urolithiasis in a Large Commercial Egg Complex in Algeria

    Directory of Open Access Journals (Sweden)

    Hicham SID

    2011-03-01

    Full Text Available Avian urolithiasis is one of the major causes of mortality in poultry. However, in Algeria this condition has never been described. An outbreak of avian urolithiasis was observed on a large commercial egg complex in the department of Chlef (West of Algeria. The clinical features of this condition are to be described. Mortality associated to urolithiasis started at the onset of egg production, estimated to 0.7 % per week. Urolithiasis induced an egg drop estimated to 12%. Dead and live layers were both necropsied and examined for kidney lesions. Most of the birds examined presented enlarged ureters, renal atrophy and visceral gout deposition.

  15. A Proactive Complex Event Processing Method for Large-Scale Transportation Internet of Things

    OpenAIRE

    Wang, Yongheng; Cao, Kening

    2014-01-01

    The Internet of Things (IoT) provides a new way to improve the transportation system. The key issue is how to process the numerous events generated by IoT. In this paper, a proactive complex event processing method is proposed for large-scale transportation IoT. Based on a multilayered adaptive dynamic Bayesian model, a Bayesian network structure learning algorithm using search-and-score is proposed to support accurate predictive analytics. A parallel Markov decision processes model is design...

  16. A Project Management Approach to Using Simulation for Cost Estimation on Large, Complex Software Development Projects

    Science.gov (United States)

    Mizell, Carolyn; Malone, Linda

    2007-01-01

    It is very difficult for project managers to develop accurate cost and schedule estimates for large, complex software development projects. None of the approaches or tools available today can estimate the true cost of software with any high degree of accuracy early in a project. This paper provides an approach that utilizes a software development process simulation model that considers and conveys the level of uncertainty that exists when developing an initial estimate. A NASA project will be analyzed using simulation and data from the Software Engineering Laboratory to show the benefits of such an approach.

  17. Management of large complex multi-stakeholders projects: a bibliometric approach

    Directory of Open Access Journals (Sweden)

    Aline Sacchi Homrich

    2017-06-01

    Full Text Available The growing global importance of large infrastructure projects has piqued the interest of many researchers in a variety of issues related to the management of large, multi-stakeholder projects, characterized by their high complexity and intense interaction among numerous stake-holders with distinct levels of responsibility. The objective of this study is to provide an overview of the academic literature focused on the management of these kinds of projects, describing the main themes considered, the lines of research identified and prominent trends. Bibliometric analysis techniques were used as well as network and content analysis. Research for information was performed in the scientific database, ISI Web of Knowledge and Scopus. The initial sample analysis consisted of 144 papers published between 1984 and 2014 and expanded to the references cited in these papers. The models identified in the literature converge with the following key-processes: project delivery systems; risk-management models; project cost management; public-private partnership.

  18. A Variable Stiffness Analysis Model for Large Complex Thin-Walled Guide Rail

    Directory of Open Access Journals (Sweden)

    Wang Xiaolong

    2016-01-01

    Full Text Available Large complex thin-walled guide rail has complicated structure and no uniform low rigidity. The traditional cutting simulations are time consuming due to huge computation especially in large workpiece. To solve these problems, a more efficient variable stiffness analysis model has been propose, which can obtain quantitative stiffness value of the machining surface. Applying simulate cutting force in sampling points using finite element analysis software ABAQUS, the single direction variable stiffness rule can be obtained. The variable stiffness matrix has been propose by analyzing multi-directions coupling variable stiffness rule. Combining with the three direction cutting force value, the reasonability of existing processing parameters can be verified and the optimized cutting parameters can be designed.

  19. A dynamic globalization model for large eddy simulation of complex turbulent flow

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hae Cheon; Park, No Ma; Kim, Jin Seok [Seoul National Univ., Seoul (Korea, Republic of)

    2005-07-01

    A dynamic subgrid-scale model is proposed for large eddy simulation of turbulent flows in complex geometry. The eddy viscosity model by Vreman [Phys. Fluids, 16, 3670 (2004)] is considered as a base model. A priori tests with the original Vreman model show that it predicts the correct profile of subgrid-scale dissipation in turbulent channel flow but the optimal model coefficient is far from universal. Dynamic procedures of determining the model coefficient are proposed based on the 'global equilibrium' between the subgrid-scale dissipation and viscous dissipation. An important feature of the proposed procedures is that the model coefficient determined is globally constant in space but varies only in time. Large eddy simulations with the present dynamic model are conducted for forced isotropic turbulence, turbulent channel flow and flow over a sphere, showing excellent agreements with previous results.

  20. Regulation of protease-activated receptor 1 signaling by the adaptor protein complex 2 and R4 subfamily of regulator of G protein signaling proteins.

    Science.gov (United States)

    Chen, Buxin; Siderovski, David P; Neubig, Richard R; Lawson, Mark A; Trejo, Joann

    2014-01-17

    The G protein-coupled protease-activated receptor 1 (PAR1) is irreversibly proteolytically activated by thrombin. Hence, the precise regulation of PAR1 signaling is important for proper cellular responses. In addition to desensitization, internalization and lysosomal sorting of activated PAR1 are critical for the termination of signaling. Unlike most G protein-coupled receptors, PAR1 internalization is mediated by the clathrin adaptor protein complex 2 (AP-2) and epsin-1, rather than β-arrestins. However, the function of AP-2 and epsin-1 in the regulation of PAR1 signaling is not known. Here, we report that AP-2, and not epsin-1, regulates activated PAR1-stimulated phosphoinositide hydrolysis via two different mechanisms that involve, in part, a subset of R4 subfamily of "regulator of G protein signaling" (RGS) proteins. A significantly greater increase in activated PAR1 signaling was observed in cells depleted of AP-2 using siRNA or in cells expressing a PAR1 (420)AKKAA(424) mutant with defective AP-2 binding. This effect was attributed to AP-2 modulation of PAR1 surface expression and efficiency of G protein coupling. We further found that ectopic expression of R4 subfamily members RGS2, RGS3, RGS4, and RGS5 reduced activated PAR1 wild-type signaling, whereas signaling by the PAR1 AKKAA mutant was minimally affected. Intriguingly, siRNA-mediated depletion analysis revealed a function for RGS5 in the regulation of signaling by the PAR1 wild type but not the AKKAA mutant. Moreover, activation of the PAR1 wild type, and not the AKKAA mutant, induced Gαq association with RGS3 via an AP-2-dependent mechanism. Thus, AP-2 regulates activated PAR1 signaling by altering receptor surface expression and through recruitment of RGS proteins.

  1. Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling

    DEFF Research Database (Denmark)

    Batth, Tanveer S; Papetti, Moreno; Pfeiffer, Anamarija

    2018-01-01

    Despite its low cellular abundance, phosphotyrosine (pTyr) regulates numerous cell signaling pathways in health and disease. We applied comprehensive phosphoproteomics to unravel differential regulators of receptor tyrosine kinase (RTK)-initiated signaling networks upon activation by Pdgf-ββ, Fgf-2...... of Pdgfr pTyr signaling. Application of a recently introduced allosteric Shp-2 inhibitor revealed global regulation of the Pdgf-dependent tyrosine phosphoproteome, which significantly impaired cell migration. In addition, we present a list of hundreds of Shp-2-dependent targets and putative substrates...

  2. β-Catenin destruction complex-independent regulation of Hippo–YAP signaling by APC in intestinal tumorigenesis

    Science.gov (United States)

    Cai, Jing; Maitra, Anirban; Anders, Robert A.; Taketo, Makoto M.; Pan, Duojia

    2015-01-01

    Mutations in Adenomatous polyposis coli (APC) underlie familial adenomatous polyposis (FAP), an inherited cancer syndrome characterized by the widespread development of colorectal polyps. APC is best known as a scaffold protein in the β-catenin destruction complex, whose activity is antagonized by canonical Wnt signaling. Whether other effector pathways mediate APC's tumor suppressor function is less clear. Here we report that activation of YAP, the downstream effector of the Hippo signaling pathway, is a general hallmark of tubular adenomas from FAP patients. We show that APC functions as a scaffold protein that facilitates the Hippo kinase cascade by interacting with Sav1 and Lats1. Consistent with the molecular link between APC and the Hippo signaling pathway, genetic analysis reveals that YAP is absolutely required for the development of APC-deficient adenomas. These findings establish Hippo–YAP signaling as a critical effector pathway downstream from APC, independent from its involvement in the β-catenin destruction complex. PMID:26193883

  3. Kurtosis based blind source extraction of complex noncircular signals with application in EEG artifact removal in real-time

    Directory of Open Access Journals (Sweden)

    Soroush eJavidi

    2011-10-01

    Full Text Available A new class of complex domain blind source extraction (BSE algorithms suitable for the extraction of both circular and noncircular complex signals is proposed. This is achieved through sequential extraction based on the degree of kurtosis and in the presence of noncircular measurement noise. The existence and uniqueness analysis of the solution is followed by a study of fast converging variants of the algorithm. The performance is first assessed through simulations on well understood benchmark signals, followed by a case study on real-time artifact removal from EEG signals, verified using both qualitative and quantitative metrics. The results illustrate the power of the proposed approach in real-time blind extraction of general complex-valued sources.

  4. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu–Gli protein complexes

    OpenAIRE

    Tukachinsky, Hanna; Lopez, Lyle V.; Salic, Adrian

    2010-01-01

    In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the transcriptional effectors of the pathway. In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu. We find that Hh stimulation quickly recruits endogenous SuFu–Gli complexes to cilia, suggesting a model in wh...

  5. Complex on the base of the ISKRA 226.6 personal computer for nuclear quadrupole resonance signal processing

    International Nuclear Information System (INIS)

    Morgunov, V.G.; Kravchenko, Eh.A.

    1988-01-01

    Complex, designed to conduct investigations by means of nuclear quadrupole resonance (NQR) method, which includes radiospectrometer, multichannel spectrum analyzer and ISKRA 226.6 personal computer, is developed. Analog-to-digital converter (ADC) with buffer storage device, interface and microcomputer are used to process NQR-signals. ADS conversion time is no more, than 50 ns, linearity - 1%. Programs on Fourier analysis of NQR-signals and calculation of relaxation times are developed

  6. Self-Tuning Linear Quadratic Supervisory Regulation of a Diesel Generator using Large-Signal State Estimation

    DEFF Research Database (Denmark)

    Knudsen, Jesper Viese; Bendtsen, Jan Dimon; Andersen, Palle

    2016-01-01

    In this paper, a self-tuning linear quadratic supervisory regulator using a large-signal state estimator for a diesel driven generator set is proposed. The regulator improves operational efficiency, in comparison to current implementations, by (i) automating the initial tuning process and (ii...... throughout the operating range of the diesel generator....

  7. Large Area Silicon Tracking Detectors with Fast Signal Readout for the Large Hadron Collider (LHC) at CERN

    CERN Document Server

    Köstner, S

    2005-01-01

    The Standard Model of elementary particles, which is summarized briefly in the second chapter, incorporates a number of successful theories to explain the nature and consistency of matter. However not all building blocks of this model could yet be tested by experiment. To confirm existing theories and to improve nowadays understanding of matter a new machine is currently being built at CERN, the Large Hadron Collider (LHC), described in the third chapter. LHC is a proton-proton collider which will reach unprecedented luminosities and center of mass energies. Five experiments are attached to it to give answers to questions like the existence of the Higgs meson, which allows to explain the mass content of matter, and the origin of CP-violation, which plays an important role in the baryogenesis of the universe. Supersymmetric theories, proposing a bosonic superpartner for each fermion and vice versa, will be tested. By colliding heavy ions, high energy and particle densities can be achieved and probed. This stat...

  8. Characterization of Aftershock Sequences from Large Strike-Slip Earthquakes Along Geometrically Complex Faults

    Science.gov (United States)

    Sexton, E.; Thomas, A.; Delbridge, B. G.

    2017-12-01

    Large earthquakes often exhibit complex slip distributions and occur along non-planar fault geometries, resulting in variable stress changes throughout the region of the fault hosting aftershocks. To better discern the role of geometric discontinuities on aftershock sequences, we compare areas of enhanced and reduced Coulomb failure stress and mean stress for systematic differences in the time dependence and productivity of these aftershock sequences. In strike-slip faults, releasing structures, including stepovers and bends, experience an increase in both Coulomb failure stress and mean stress during an earthquake, promoting fluid diffusion into the region and further failure. Conversely, Coulomb failure stress and mean stress decrease in restraining bends and stepovers in strike-slip faults, and fluids diffuse away from these areas, discouraging failure. We examine spatial differences in seismicity patterns along structurally complex strike-slip faults which have hosted large earthquakes, such as the 1992 Mw 7.3 Landers, the 2010 Mw 7.2 El-Mayor Cucapah, the 2014 Mw 6.0 South Napa, and the 2016 Mw 7.0 Kumamoto events. We characterize the behavior of these aftershock sequences with the Epidemic Type Aftershock-Sequence Model (ETAS). In this statistical model, the total occurrence rate of aftershocks induced by an earthquake is λ(t) = λ_0 + \\sum_{i:t_i

  9. Wall modeled large eddy simulations of complex high Reynolds number flows with synthetic inlet turbulence

    International Nuclear Information System (INIS)

    Patil, Sunil; Tafti, Danesh

    2012-01-01

    Highlights: ► Large eddy simulation. ► Wall layer modeling. ► Synthetic inlet turbulence. ► Swirl flows. - Abstract: Large eddy simulations of complex high Reynolds number flows are carried out with the near wall region being modeled with a zonal two layer model. A novel formulation for solving the turbulent boundary layer equation for the effective tangential velocity in a generalized co-ordinate system is presented and applied in the near wall zonal treatment. This formulation reduces the computational time in the inner layer significantly compared to the conventional two layer formulations present in the literature and is most suitable for complex geometries involving body fitted structured and unstructured meshes. The cost effectiveness and accuracy of the proposed wall model, used with the synthetic eddy method (SEM) to generate inlet turbulence, is investigated in turbulent channel flow, flow over a backward facing step, and confined swirling flows at moderately high Reynolds numbers. Predictions are compared with available DNS, experimental LDV data, as well as wall resolved LES. In all cases, there is at least an order of magnitude reduction in computational cost with no significant loss in prediction accuracy.

  10. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes.

    Science.gov (United States)

    Tukachinsky, Hanna; Lopez, Lyle V; Salic, Adrian

    2010-10-18

    In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the transcriptional effectors of the pathway. In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu. We find that Hh stimulation quickly recruits endogenous SuFu-Gli complexes to cilia, suggesting a model in which Smo activates Gli by relieving inhibition by SuFu. In support of this model, we find that Hh causes rapid dissociation of the SuFu-Gli complex, thus allowing Gli to enter the nucleus and activate transcription. Activation of protein kinase A (PKA), an inhibitor of Hh signaling, blocks ciliary localization of SuFu-Gli complexes, which in turn prevents their dissociation by signaling. Our results support a simple mechanism in which Hh signals at vertebrate cilia cause dissociation of inactive SuFu-Gli complexes, a process inhibited by PKA.

  11. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu–Gli protein complexes

    Science.gov (United States)

    Tukachinsky, Hanna; Lopez, Lyle V.

    2010-01-01

    In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the transcriptional effectors of the pathway. In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu. We find that Hh stimulation quickly recruits endogenous SuFu–Gli complexes to cilia, suggesting a model in which Smo activates Gli by relieving inhibition by SuFu. In support of this model, we find that Hh causes rapid dissociation of the SuFu–Gli complex, thus allowing Gli to enter the nucleus and activate transcription. Activation of protein kinase A (PKA), an inhibitor of Hh signaling, blocks ciliary localization of SuFu–Gli complexes, which in turn prevents their dissociation by signaling. Our results support a simple mechanism in which Hh signals at vertebrate cilia cause dissociation of inactive SuFu–Gli complexes, a process inhibited by PKA. PMID:20956384

  12. Rheb may complex with RASSF1A to coordinate Hippo and TOR signaling.

    Science.gov (United States)

    Nelson, Nicholas; Clark, Geoffrey J

    2016-06-07

    The TOR pathway is a vital component of cellular homeostasis that controls the synthesis of proteins, nucleic acids and lipids. Its core is the TOR kinase. Activation of the TOR pathway suppresses autophagy, which plays a vital but complex role in tumorigenesis. The TOR pathway is regulated by activation of the Ras-related protein Rheb, which can bind mTOR. The Hippo pathway is a major growth control module that regulates cell growth, differentiation and apoptosis. Its core consists of an MST/LATS kinase cascade that can be activated by the RASSF1A tumor suppressor. The TOR and Hippo pathways may be coordinately regulated to promote cellular homeostasis. However, the links between the pathways remain only partially understood. We now demonstrate that in addition to mTOR regulation, Rheb also impacts the Hippo pathway by forming a complex with RASSF1A. Using stable clones of two human lung tumor cell lines (NCI-H1792 and NCI-H1299) with shRNA-mediated silencing or ectopic overexpression of RASSF1A, we show that activated Rheb stimulates the Hippo pathway, but is suppressed in its ability to stimulate the TOR pathway. Moreover, by selectively labeling autophagic vacuoles we show that RASSF1A inhibits the ability of Rheb to suppress autophagy and enhance cell growth. Thus, we identify a new connection that impacts coordination of Hippo and TOR signaling. As RASSF1A expression is frequently lost in human tumors, the RASSF1A status of a tumor may impact not just its Hippo pathway status, but also its TOR pathway status.

  13. Large-Signal Lyapunov-Based Stability Analysis of DC/AC Inverters and Inverter-Based Microgrids

    Science.gov (United States)

    Kabalan, Mahmoud

    Microgrid stability studies have been largely based on small-signal linearization techniques. However, the validity and magnitude of the linearization domain is limited to small perturbations. Thus, there is a need to examine microgrids with large-signal nonlinear techniques to fully understand and examine their stability. Large-signal stability analysis can be accomplished by Lyapunov-based mathematical methods. These Lyapunov methods estimate the domain of asymptotic stability of the studied system. A survey of Lyapunov-based large-signal stability studies showed that few large-signal studies have been completed on either individual systems (dc/ac inverters, dc/dc rectifiers, etc.) or microgrids. The research presented in this thesis addresses the large-signal stability of droop-controlled dc/ac inverters and inverter-based microgrids. Dc/ac power electronic inverters allow microgrids to be technically feasible. Thus, as a prelude to examining the stability of microgrids, the research presented in Chapter 3 analyzes the stability of inverters. First, the 13 th order large-signal nonlinear model of a droop-controlled dc/ac inverter connected to an infinite bus is presented. The singular perturbation method is used to decompose the nonlinear model into 11th, 9th, 7th, 5th, 3rd and 1st order models. Each model ignores certain control or structural components of the full order model. The aim of the study is to understand the accuracy and validity of the reduced order models in replicating the performance of the full order nonlinear model. The performance of each model is studied in three different areas: time domain simulations, Lyapunov's indirect method and domain of attraction estimation. The work aims to present the best model to use in each of the three domains of study. Results show that certain reduced order models are capable of accurately reproducing the performance of the full order model while others can be used to gain insights into those three areas of

  14. Fast and accurate detection of spread source in large complex networks.

    Science.gov (United States)

    Paluch, Robert; Lu, Xiaoyan; Suchecki, Krzysztof; Szymański, Bolesław K; Hołyst, Janusz A

    2018-02-06

    Spread over complex networks is a ubiquitous process with increasingly wide applications. Locating spread sources is often important, e.g. finding the patient one in epidemics, or source of rumor spreading in social network. Pinto, Thiran and Vetterli introduced an algorithm (PTVA) to solve the important case of this problem in which a limited set of nodes act as observers and report times at which the spread reached them. PTVA uses all observers to find a solution. Here we propose a new approach in which observers with low quality information (i.e. with large spread encounter times) are ignored and potential sources are selected based on the likelihood gradient from high quality observers. The original complexity of PTVA is O(N α ), where α ∈ (3,4) depends on the network topology and number of observers (N denotes the number of nodes in the network). Our Gradient Maximum Likelihood Algorithm (GMLA) reduces this complexity to O (N 2 log (N)). Extensive numerical tests performed on synthetic networks and real Gnutella network with limitation that id's of spreaders are unknown to observers demonstrate that for scale-free networks with such limitation GMLA yields higher quality localization results than PTVA does.

  15. The method of measurement and synchronization control for large-scale complex loading system

    International Nuclear Information System (INIS)

    Liao Min; Li Pengyuan; Hou Binglin; Chi Chengfang; Zhang Bo

    2012-01-01

    With the development of modern industrial technology, measurement and control system was widely used in high precision, complex industrial control equipment and large-tonnage loading device. The measurement and control system is often used to analyze the distribution of stress and displacement in the complex bearing load or the complex nature of the mechanical structure itself. In ITER GS mock-up with 5 flexible plates, for each load combination, detect and measure potential slippage between the central flexible plate and the neighboring spacers is necessary as well as the potential slippage between each pre-stressing bar and its neighboring plate. The measurement and control system consists of seven sets of EDC controller and board, computer system, 16-channel quasi-dynamic strain gauge, 25 sets of displacement sensors, 7 sets of load and displacement sensors in the cylinders. This paper demonstrates the principles and methods of EDC220 digital controller to achieve synchronization control, and R and D process of multi-channel loading control software and measurement software. (authors)

  16. Megacities and Large Urban Complexes - WMO Role in Addressing Challenges and Opportunities

    Science.gov (United States)

    Terblanche, Deon; Jalkanen, Liisa

    2013-04-01

    Megacities and Large Urban Complexes - WMO Role in Addressing Challenges and Opportunities Deon E. Terblanche and Liisa Jalkanen dterblanche@wmo.int ljalkanen@wmo.int World Meteorological Organization, Geneva, Switzerland The 21st Century could amongst others, become known as the century in which our species has evolved from Homo sapiens to Homo urbanus. By now the urban population has surpassed the rural population and the rate of urbanization will continue at such a pace that by 2050 urban dwellers could outnumber their rural counterpart by more than two to one. Most of this growth in urban population will occur in developing countries and along coastal areas. Urbanization is to a large extent the outcome of humans seeking a better life through improved opportunities presented by high-density communities. Megacities and large urban complexes provide more job opportunities and social structures, better transport and communication links and a relative abundance of physical goods and services when compared to most rural areas. Unfortunately these urban complexes also present numerous social and environmental challenges. Urban areas differ from their surroundings by morphology, population density, and with high concentration of industrial activities, energy consumption and transport. They also pose unique challenges to atmospheric modelling and monitoring and create a multi-disciplinary spectrum of potential threats, including air pollution, which need to be addressed in an integrated way. These areas are also vulnerable to the changing climate and its implications to sea-level and extreme events, air quality and related health impacts. Many urban activities are significantly impacted by weather events that would not be considered to be of high impact in less densely populated areas. For instance, moderate precipitation events can cause flooding and landslides as modified urban catchments generally have higher run-off to rainfall ratios than their more pristine rural

  17. Organizational Influences on Interdisciplinary Interactions during Research and Design of Large-Scale Complex Engineered Systems

    Science.gov (United States)

    McGowan, Anna-Maria R.; Seifert, Colleen M.; Papalambros, Panos Y.

    2012-01-01

    The design of large-scale complex engineered systems (LaCES) such as an aircraft is inherently interdisciplinary. Multiple engineering disciplines, drawing from a team of hundreds to thousands of engineers and scientists, are woven together throughout the research, development, and systems engineering processes to realize one system. Though research and development (R&D) is typically focused in single disciplines, the interdependencies involved in LaCES require interdisciplinary R&D efforts. This study investigates the interdisciplinary interactions that take place during the R&D and early conceptual design phases in the design of LaCES. Our theoretical framework is informed by both engineering practices and social science research on complex organizations. This paper provides preliminary perspective on some of the organizational influences on interdisciplinary interactions based on organization theory (specifically sensemaking), data from a survey of LaCES experts, and the authors experience in the research and design. The analysis reveals couplings between the engineered system and the organization that creates it. Survey respondents noted the importance of interdisciplinary interactions and their significant benefit to the engineered system, such as innovation and problem mitigation. Substantial obstacles to interdisciplinarity are uncovered beyond engineering that include communication and organizational challenges. Addressing these challenges may ultimately foster greater efficiencies in the design and development of LaCES and improved system performance by assisting with the collective integration of interdependent knowledge bases early in the R&D effort. This research suggests that organizational and human dynamics heavily influence and even constrain the engineering effort for large-scale complex systems.

  18. Sensemaking in a Value Based Context for Large Scale Complex Engineered Systems

    Science.gov (United States)

    Sikkandar Basha, Nazareen

    The design and the development of Large-Scale Complex Engineered Systems (LSCES) requires the involvement of multiple teams and numerous levels of the organization and interactions with large numbers of people and interdisciplinary departments. Traditionally, requirements-driven Systems Engineering (SE) is used in the design and development of these LSCES. The requirements are used to capture the preferences of the stakeholder for the LSCES. Due to the complexity of the system, multiple levels of interactions are required to elicit the requirements of the system within the organization. Since LSCES involves people and interactions between the teams and interdisciplinary departments, it should be socio-technical in nature. The elicitation of the requirements of most large-scale system projects are subjected to creep in time and cost due to the uncertainty and ambiguity of requirements during the design and development. In an organization structure, the cost and time overrun can occur at any level and iterate back and forth thus increasing the cost and time. To avoid such creep past researches have shown that rigorous approaches such as value based designing can be used to control it. But before the rigorous approaches can be used, the decision maker should have a proper understanding of requirements creep and the state of the system when the creep occurs. Sensemaking is used to understand the state of system when the creep occurs and provide a guidance to decision maker. This research proposes the use of the Cynefin framework, sensemaking framework which can be used in the design and development of LSCES. It can aide in understanding the system and decision making to minimize the value gap due to requirements creep by eliminating ambiguity which occurs during design and development. A sample hierarchical organization is used to demonstrate the state of the system at the occurrence of requirements creep in terms of cost and time using the Cynefin framework. These

  19. Combining eastern and western practices for safe and effective endoscopic resection of large complex colorectal lesions.

    Science.gov (United States)

    Emmanuel, Andrew; Gulati, Shraddha; Burt, Margaret; Hayee, Bu'Hussain; Haji, Amyn

    2018-05-01

    Endoscopic resection of large colorectal polyps is well established. However, significant differences in technique exist between eastern and western interventional endoscopists. We report the results of endoscopic resection of large complex colorectal lesions from a specialist unit that combines eastern and western techniques for assessment and resection. Endoscopic resections of colorectal lesions of at least 2 cm were included. Lesions were assessed using magnification chromoendoscopy supplemented by colonoscopic ultrasound in selected cases. A lesion-specific approach to resection with endoscopic mucosal resection or endoscopic submucosal dissection (ESD) was used. Surveillance endoscopy was performed at 3 (SC1) and 12 (SC2) months. Four hundred and sixty-six large (≥20 mm) colorectal lesions (mean size 54.8 mm) were resected. Three hundread and fifty-six were resected using endoscopic mucosal resection and 110 by ESD or hybrid ESD. Fifty-one percent of lesions had been subjected to previous failed attempts at resection or heavy manipulation (≥6 biopsies). Nevertheless, endoscopic resection was deemed successful after an initial attempt in 98%. Recurrence occurred in 15% and could be treated with endoscopic resection in most. Only two patients required surgery for perforation. Nine patients had postprocedure bleeding; only two required endoscopic clips. Ninety-six percent of patients without invasive cancer were free from recurrence and had avoided surgery at last follow-up. Combining eastern and western practices for assessment and resection results in safe and effective organ-conserving treatment of complex colorectal lesions. Accurate assessment before and after resection using magnification chromoendoscopy and a lesion-specific approach to resection, incorporating ESD where appropriate, are important factors in achieving these results.

  20. Therapeutic Targeting of the IL-6 Trans-Signaling/Mechanistic Target of Rapamycin Complex 1 Axis in Pulmonary Emphysema.

    Science.gov (United States)

    Ruwanpura, Saleela M; McLeod, Louise; Dousha, Lovisa F; Seow, Huei J; Alhayyani, Sultan; Tate, Michelle D; Deswaerte, Virginie; Brooks, Gavin D; Bozinovski, Steven; MacDonald, Martin; Garbers, Christoph; King, Paul T; Bardin, Philip G; Vlahos, Ross; Rose-John, Stefan; Anderson, Gary P; Jenkins, Brendan J

    2016-12-15

    The potent immunomodulatory cytokine IL-6 is consistently up-regulated in human lungs with emphysema and in mouse emphysema models; however, the mechanisms by which IL-6 promotes emphysema remain obscure. IL-6 signals using two distinct modes: classical signaling via its membrane-bound IL-6 receptor (IL-6R), and trans-signaling via a naturally occurring soluble IL-6R. To identify whether IL-6 trans-signaling and/or classical signaling contribute to the pathogenesis of emphysema. We used the gp130 F/F genetic mouse model for spontaneous emphysema and cigarette smoke-induced emphysema models. Emphysema in mice was quantified by various methods including in vivo lung function and stereology, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to assess alveolar cell apoptosis. In mouse and human lung tissues, the expression level and location of IL-6 signaling-related genes and proteins were measured, and the levels of IL-6 and related proteins in sera from emphysematous mice and patients were also assessed. Lung tissues from patients with emphysema, and from spontaneous and cigarette smoke-induced emphysema mouse models, were characterized by excessive production of soluble IL-6R. Genetic blockade of IL-6 trans-signaling in emphysema mouse models and therapy with the IL-6 trans-signaling antagonist sgp130Fc ameliorated emphysema by suppressing augmented alveolar type II cell apoptosis. Furthermore, IL-6 trans-signaling-driven emphysematous changes in the lung correlated with mechanistic target of rapamycin complex 1 hyperactivation, and treatment of emphysema mouse models with the mechanistic target of rapamycin complex 1 inhibitor rapamycin attenuated emphysematous changes. Collectively, our data reveal that specific targeting of IL-6 trans-signaling may represent a novel treatment strategy for emphysema.

  1. SUMO-, MAPK- and resistance protein-signaling converge at transcription complexes that regulate plant innate immunity

    NARCIS (Netherlands)

    Burg, van den H.A.; Takken, F.L.W.

    2010-01-01

    Upon pathogen perception plant innate immune receptors activate various signaling pathways that trigger host defenses. PAMP-triggered defense signaling requires mitogen-activated protein kinase (MAPK) pathways, which modulate the activity of transcription factors through phosphorylation. Here, we

  2. SUMO-, MAPK-, and resistance protein-signaling converge at transcription complexes that regulate plant innate immunity

    NARCIS (Netherlands)

    van den Burg, H.A.; Takken, F.L.W.

    2010-01-01

    Upon pathogen perception plant innate immune receptors activate various signaling pathways that trigger host defenses. PAMP-triggered defense signaling requires mitogen-activated protein kinase (MAPK) pathways, which modulate the activity of transcription factors through phosphorylation. Here, we

  3. Evaluation model of project complexity for large-scale construction projects in Iran - A Fuzzy ANP approach

    Directory of Open Access Journals (Sweden)

    Aliyeh Kazemi

    2016-09-01

    Full Text Available Construction projects have always been complex. By growing trend of this complexity, implementations of large-scale constructions become harder. Hence, evaluating and understanding these complexities are critical. Correct evaluation of a project complication can provide executives and managers with good source to use. Fuzzy analytic network process (ANP is a logical and systematic approach toward defining, evaluation, and grading. This method allows for analyzing complex systems, and determining complexity of them. In this study, by taking advantage of fuzzy ANP, effective indexes for development of complications in large-scale construction projects in Iran have been determined and prioritized. The results show socio-political, project system interdependencies, and technological complexity indexes ranked top to three. Furthermore, in comparison of three main huge projects: commercial-administrative, hospital, and skyscrapers, the hospital project had been evaluated as the most complicated. This model is beneficial for professionals in managing large-scale projects.

  4. Analysis of Maneuvering Targets with Complex Motions by Two-Dimensional Product Modified Lv's Distribution for Quadratic Frequency Modulation Signals.

    Science.gov (United States)

    Jing, Fulong; Jiao, Shuhong; Hou, Changbo; Si, Weijian; Wang, Yu

    2017-06-21

    For targets with complex motion, such as ships fluctuating with oceanic waves and high maneuvering airplanes, azimuth echo signals can be modeled as multicomponent quadratic frequency modulation (QFM) signals after migration compensation and phase adjustment. For the QFM signal model, the chirp rate (CR) and the quadratic chirp rate (QCR) are two important physical quantities, which need to be estimated. For multicomponent QFM signals, the cross terms create a challenge for detection, which needs to be addressed. In this paper, by employing a novel multi-scale parametric symmetric self-correlation function (PSSF) and modified scaled Fourier transform (mSFT), an effective parameter estimation algorithm is proposed-referred to as the Two-Dimensional product modified Lv's distribution (2D-PMLVD)-for QFM signals. The 2D-PMLVD is simple and can be easily implemented by using fast Fourier transform (FFT) and complex multiplication. These measures are analyzed in the paper, including the principle, the cross term, anti-noise performance, and computational complexity. Compared to the other three representative methods, the 2D-PMLVD can achieve better anti-noise performance. The 2D-PMLVD, which is free of searching and has no identifiability problems, is more suitable for multicomponent situations. Through several simulations and analyses, the effectiveness of the proposed estimation algorithm is verified.

  5. Packaging Concerns and Techniques for Large Devices: Challenges for Complex Electronics

    Science.gov (United States)

    LaBel, Kenneth A.; Sampson, Michael J.

    2010-01-01

    NASA is going to have to accept the use of non-hermetic packages for complex devices. There are a large number of packaging options available. Space application subjects the packages to stresses that they were probably not designed for (vacuum for instance). NASA has to find a way of having assurance in the integrity of the packages. There are manufacturers interested in qualifying non-hermetic packages to MIL-PRF-38535 Class V. Government space users are agreed that Class V should be for hermetic packages only. NASA is working on a new Class for non-hermetic packages for M38535 Appendix B, "Class Y". Testing for package integrity will be required but can be package specific as described by a Package Integrity Test Plan. The plan is developed by the manufacturer and approved by DSCC and government space.

  6. Complex dewetting scenarios of ultrathin silicon films for large-scale nanoarchitectures.

    Science.gov (United States)

    Naffouti, Meher; Backofen, Rainer; Salvalaglio, Marco; Bottein, Thomas; Lodari, Mario; Voigt, Axel; David, Thomas; Benkouider, Abdelmalek; Fraj, Ibtissem; Favre, Luc; Ronda, Antoine; Berbezier, Isabelle; Grosso, David; Abbarchi, Marco; Bollani, Monica

    2017-11-01

    Dewetting is a ubiquitous phenomenon in nature; many different thin films of organic and inorganic substances (such as liquids, polymers, metals, and semiconductors) share this shape instability driven by surface tension and mass transport. Via templated solid-state dewetting, we frame complex nanoarchitectures of monocrystalline silicon on insulator with unprecedented precision and reproducibility over large scales. Phase-field simulations reveal the dominant role of surface diffusion as a driving force for dewetting and provide a predictive tool to further engineer this hybrid top-down/bottom-up self-assembly method. Our results demonstrate that patches of thin monocrystalline films of metals and semiconductors share the same dewetting dynamics. We also prove the potential of our method by fabricating nanotransfer molding of metal oxide xerogels on silicon and glass substrates. This method allows the novel possibility of transferring these Si-based patterns on different materials, which do not usually undergo dewetting, offering great potential also for microfluidic or sensing applications.

  7. Task Phase Recognition for Highly Mobile Workers in Large Building Complexes

    DEFF Research Database (Denmark)

    Stisen, Allan; Mathisen, Andreas; Krogh, Søren

    2016-01-01

    requirements on the accuracy of the indoor positioning, and thus come with low deployment and maintenance effort in real-world settings. We evaluated the proposed methods in a large hospital complex, where the highly mobile workers were recruited among the non-clinical workforce. The evaluation is based......-scale indoor work environments, namely from a WiFi infrastructure providing coarse grained indoor positioning, from inertial sensors in the workers’ mobile phones, and from a task management system yielding information about the scheduled tasks’ start and end locations. The methods presented have low...... on manually labelled real-world data collected over 4 days of regular work life of the mobile workforce. The collected data yields 83 tasks in total involving 8 different orderlies from a major university hospital with a building area of 160, 000 m2. The results show that the proposed methods can distinguish...

  8. A lossless multichannel bio-signal compression based on low-complexity joint coding scheme for portable medical devices.

    Science.gov (United States)

    Kim, Dong-Sun; Kwon, Jin-San

    2014-09-18

    Research on real-time health systems have received great attention during recent years and the needs of high-quality personal multichannel medical signal compression for personal medical product applications are increasing. The international MPEG-4 audio lossless coding (ALS) standard supports a joint channel-coding scheme for improving compression performance of multichannel signals and it is very efficient compression method for multi-channel biosignals. However, the computational complexity of such a multichannel coding scheme is significantly greater than that of other lossless audio encoders. In this paper, we present a multichannel hardware encoder based on a low-complexity joint-coding technique and shared multiplier scheme for portable devices. A joint-coding decision method and a reference channel selection scheme are modified for a low-complexity joint coder. The proposed joint coding decision method determines the optimized joint-coding operation based on the relationship between the cross correlation of residual signals and the compression ratio. The reference channel selection is designed to select a channel for the entropy coding of the joint coding. The hardware encoder operates at a 40 MHz clock frequency and supports two-channel parallel encoding for the multichannel monitoring system. Experimental results show that the compression ratio increases by 0.06%, whereas the computational complexity decreases by 20.72% compared to the MPEG-4 ALS reference software encoder. In addition, the compression ratio increases by about 11.92%, compared to the single channel based bio-signal lossless data compressor.

  9. Fixed-Point Algorithms for the Blind Separation of Arbitrary Complex-Valued Non-Gaussian Signal Mixtures

    Directory of Open Access Journals (Sweden)

    Douglas Scott C

    2007-01-01

    Full Text Available We derive new fixed-point algorithms for the blind separation of complex-valued mixtures of independent, noncircularly symmetric, and non-Gaussian source signals. Leveraging recently developed results on the separability of complex-valued signal mixtures, we systematically construct iterative procedures on a kurtosis-based contrast whose evolutionary characteristics are identical to those of the FastICA algorithm of Hyvarinen and Oja in the real-valued mixture case. Thus, our methods inherit the fast convergence properties, computational simplicity, and ease of use of the FastICA algorithm while at the same time extending this class of techniques to complex signal mixtures. For extracting multiple sources, symmetric and asymmetric signal deflation procedures can be employed. Simulations for both noiseless and noisy mixtures indicate that the proposed algorithms have superior finite-sample performance in data-starved scenarios as compared to existing complex ICA methods while performing about as well as the best of these techniques for larger data-record lengths.

  10. Bcl-xL acts downstream of caspase-8 activation by the CD95 death-inducing signaling complex

    NARCIS (Netherlands)

    Medema, J. P.; Scaffidi, C.; Krammer, P. H.; Peter, M. E.

    1998-01-01

    The Bcl-2 family member Bcl-xL has often been correlated with apoptosis resistance. We have shown recently that in peripheral human T cells resistance to CD95-mediated apoptosis is characterized by a lack of caspase-8 recruitment to the CD95 death-inducing signaling complex (DISC) and by increased

  11. Investigation of the complexity of streamflow fluctuations in a large heterogeneous lake catchment in China

    Science.gov (United States)

    Ye, Xuchun; Xu, Chong-Yu; Li, Xianghu; Zhang, Qi

    2018-05-01

    The occurrence of flood and drought frequency is highly correlated with the temporal fluctuations of streamflow series; understanding of these fluctuations is essential for the improved modeling and statistical prediction of extreme changes in river basins. In this study, the complexity of daily streamflow fluctuations was investigated by using multifractal detrended fluctuation analysis (MF-DFA) in a large heterogeneous lake basin, the Poyang Lake basin in China, and the potential impacts of human activities were also explored. Major results indicate that the multifractality of streamflow fluctuations shows significant regional characteristics. In the study catchment, all the daily streamflow series present a strong long-range correlation with Hurst exponents bigger than 0.8. The q-order Hurst exponent h( q) of all the hydrostations can be characterized well by only two parameters: a (0.354 ≤ a ≤ 0.384) and b (0.627 ≤ b ≤ 0.677), with no pronounced differences. Singularity spectrum analysis pointed out that small fluctuations play a dominant role in all daily streamflow series. Our research also revealed that both the correlation properties and the broad probability density function (PDF) of hydrological series can be responsible for the multifractality of streamflow series that depends on watershed areas. In addition, we emphasized the relationship between watershed area and the estimated multifractal parameters, such as the Hurst exponent and fitted parameters a and b from the q-order Hurst exponent h( q). However, the relationship between the width of the singularity spectrum (Δ α) and watershed area is not clear. Further investigation revealed that increasing forest coverage and reservoir storage can effectively enhance the persistence of daily streamflow, decrease the hydrological complexity of large fluctuations, and increase the small fluctuations.

  12. Pseudo-stokes vector from complex signal representation of a speckle pattern and its applications to micro-displacement measurement

    DEFF Research Database (Denmark)

    Wang, W.; Ishijima, R.; Matsuda, A.

    2010-01-01

    As an improvement of the intensity correlation used widely in conventional electronic speckle photography, we propose a new technique for displacement measurement based on correlating Stokes-like parameters derivatives for transformed speckle patterns. The method is based on a Riesz transform of ...... are presented that demonstrate the validity and advantage of the proposed pseudo-Stokes vector correlation technique over conventional intensity correlation technique....... of the intensity speckle pattern, which converts the original real-valued signal into a complex signal. In closest analogy to the polarisation of a vector wave, the Stokes-like vector constructed from the spatial derivative of the generated complex signal has been applied for correlation. Experimental results...

  13. Analysis of progression of fatigue conditions in biceps brachii muscles using surface electromyography signals and complexity based features.

    Science.gov (United States)

    Karthick, P A; Makaram, Navaneethakrishna; Ramakrishnan, S

    2014-01-01

    Muscle fatigue is a neuromuscular condition where muscle performance decreases due to sustained or intense contraction. It is experienced by both normal and abnormal subjects. In this work, an attempt has been made to analyze the progression of muscle fatigue in biceps brachii muscles using surface electromyography (sEMG) signals. The sEMG signals are recorded from fifty healthy volunteers during dynamic contractions under well defined protocol. The acquired signals are preprocessed and segmented in to six equal parts for further analysis. The features, such as activity, mobility, complexity, sample entropy and spectral entropy are extracted from all six zones. The results are found showing that the extracted features except complexity feature have significant variations in differentiating non-fatigue and fatigue zone respectively. Thus, it appears that, these features are useful in automated analysis of various neuromuscular activities in normal and pathological conditions.

  14. A large-eddy simulation based power estimation capability for wind farms over complex terrain

    Science.gov (United States)

    Senocak, I.; Sandusky, M.; Deleon, R.

    2017-12-01

    There has been an increasing interest in predicting wind fields over complex terrain at the micro-scale for resource assessment, turbine siting, and power forecasting. These capabilities are made possible by advancements in computational speed from a new generation of computing hardware, numerical methods and physics modelling. The micro-scale wind prediction model presented in this work is based on the large-eddy simulation paradigm with surface-stress parameterization. The complex terrain is represented using an immersed-boundary method that takes into account the parameterization of the surface stresses. Governing equations of incompressible fluid flow are solved using a projection method with second-order accurate schemes in space and time. We use actuator disk models with rotation to simulate the influence of turbines on the wind field. Data regarding power production from individual turbines are mostly restricted because of proprietary nature of the wind energy business. Most studies report percentage drop of power relative to power from the first row. There have been different approaches to predict power production. Some studies simply report available wind power in the upstream, some studies estimate power production using power curves available from turbine manufacturers, and some studies estimate power as torque multiplied by rotational speed. In the present work, we propose a black-box approach that considers a control volume around a turbine and estimate the power extracted from the turbine based on the conservation of energy principle. We applied our wind power prediction capability to wind farms over flat terrain such as the wind farm over Mower County, Minnesota and the Horns Rev offshore wind farm in Denmark. The results from these simulations are in good agreement with published data. We also estimate power production from a hypothetical wind farm in complex terrain region and identify potential zones suitable for wind power production.

  15. Benchmarking of London Dispersion-Accounting Density Functional Theory Methods on Very Large Molecular Complexes.

    Science.gov (United States)

    Risthaus, Tobias; Grimme, Stefan

    2013-03-12

    A new test set (S12L) containing 12 supramolecular noncovalently bound complexes is presented and used to evaluate seven different methods to account for dispersion in DFT (DFT-D3, DFT-D2, DFT-NL, XDM, dDsC, TS-vdW, M06-L) at different basis set levels against experimental, back-corrected reference energies. This allows conclusions about the performance of each method in an explorative research setting on "real-life" problems. Most DFT methods show satisfactory performance but, due to the largeness of the complexes, almost always require an explicit correction for the nonadditive Axilrod-Teller-Muto three-body dispersion interaction to get accurate results. The necessity of using a method capable of accounting for dispersion is clearly demonstrated in that the two-body dispersion contributions are on the order of 20-150% of the total interaction energy. MP2 and some variants thereof are shown to be insufficient for this while a few tested D3-corrected semiempirical MO methods perform reasonably well. Overall, we suggest the use of this benchmark set as a "sanity check" against overfitting to too small molecular cases.

  16. Low Complexity Precoder and Receiver Design for Massive MIMO Systems: A Large System Analysis using Random Matrix Theory

    KAUST Repository

    Sifaou, Houssem

    2016-05-01

    Massive MIMO systems are shown to be a promising technology for next generations of wireless communication networks. The realization of the attractive merits promised by massive MIMO systems requires advanced linear precoding and receiving techniques in order to mitigate the interference in downlink and uplink transmissions. This work considers the precoder and receiver design in massive MIMO systems. We first consider the design of the linear precoder and receiver that maximize the minimum signal-to-interference-plus-noise ratio (SINR) subject to a given power constraint. The analysis is carried out under the asymptotic regime in which the number of the BS antennas and that of the users grow large with a bounded ratio. This allows us to leverage tools from random matrix theory in order to approximate the parameters of the optimal linear precoder and receiver by their deterministic approximations. Such a result is of valuable practical interest, as it provides a handier way to implement the optimal precoder and receiver. To reduce further the complexity, we propose to apply the truncated polynomial expansion (TPE) concept on a per-user basis to approximate the inverse of large matrices that appear on the expressions of the optimal linear transceivers. Using tools from random matrix theory, we determine deterministic approximations of the SINR and the transmit power in the asymptotic regime. Then, the optimal per-user weight coe cients that solve the max-min SINR problem are derived. The simulation results show that the proposed precoder and receiver provide very close to optimal performance while reducing signi cantly the computational complexity. As a second part of this work, the TPE technique in a per-user basis is applied to the optimal linear precoding that minimizes the transmit power while satisfying a set of target SINR constraints. Due to the emerging research eld of green cellular networks, such a problem is receiving increasing interest nowadays. Closed

  17. An Adaptive Noise Cancellation System Based on Linear and Widely Linear Complex Valued Least Mean Square Algorithms for Removing Electrooculography Artifacts from Electroencephalography Signals

    Directory of Open Access Journals (Sweden)

    Engin Cemal MENGÜÇ

    2018-03-01

    Full Text Available In this study, an adaptive noise cancellation (ANC system based on linear and widely linear (WL complex valued least mean square (LMS algorithms is designed for removing electrooculography (EOG artifacts from electroencephalography (EEG signals. The real valued EOG and EEG signals (Fp1 and Fp2 given in dataset are primarily expressed as a complex valued signal in the complex domain. Then, using the proposed ANC system, the EOG artifacts are eliminated in the complex domain from the EEG signals. Expression of these signals in the complex domain allows us to remove EOG artifacts from two EEG channels simultaneously. Moreover, in this study, it has been shown that the complex valued EEG signal exhibits noncircular behavior, and in the case, the WL-CLMS algorithm enhances the performance of the ANC system compared to real-valued LMS and CLMS algorithms. Simulation results support the proposed approach.

  18. How to Commission, Operate and Maintain a Large Future Accelerator Complex From Far Remote Sites

    International Nuclear Information System (INIS)

    Phinney, Nan

    2001-01-01

    A study on future large accelerators [1] has considered a facility, which is designed, built and operated by a worldwide collaboration of equal partner institutions, and which is remote from most of these institutions. The full range of operation was considered including commissioning, machine development, maintenance, trouble shooting and repair. Experience from existing accelerators confirms that most of these activities are already performed remotely. The large high-energy physics experiments and astronomy projects, already involve international collaborations of distant institutions. Based on this experience, the prospects for a machine operated remotely from far sites are encouraging. Experts from each laboratory would remain at their home institution but continue to participate in the operation of the machine after construction. Experts are required to be on site only during initial commissioning and for particularly difficult problems. Repairs require an on-site non-expert maintenance crew. Most of the interventions can be made without an expert and many of the rest resolved with remote assistance. There appears to be no technical obstacle to controlling an accelerator from a distance. The major challenge is to solve the complex management and communication problems

  19. The Detection of Hot Cores and Complex Organic Molecules in the Large Magellanic Cloud

    Science.gov (United States)

    Sewiło, Marta; Indebetouw, Remy; Charnley, Steven B.; Zahorecz, Sarolta; Oliveira, Joana M.; van Loon, Jacco Th.; Ward, Jacob L.; Chen, C.-H. Rosie; Wiseman, Jennifer; Fukui, Yasuo; Kawamura, Akiko; Meixner, Margaret; Onishi, Toshikazu; Schilke, Peter

    2018-02-01

    We report the first extragalactic detection of the complex organic molecules (COMs) dimethyl ether (CH3OCH3) and methyl formate (CH3OCHO) with the Atacama Large Millimeter/submillimeter Array (ALMA). These COMs, together with their parent species methanol (CH3OH), were detected toward two 1.3 mm continuum sources in the N 113 star-forming region in the low-metallicity Large Magellanic Cloud (LMC). Rotational temperatures ({T}{rot}∼ 130 K) and total column densities ({N}{rot}∼ {10}16 cm‑2) have been calculated for each source based on multiple transitions of CH3OH. We present the ALMA molecular emission maps for COMs and measured abundances for all detected species. The physical and chemical properties of two sources with COMs detection, and the association with H2O and OH maser emission, indicate that they are hot cores. The fractional abundances of COMs scaled by a factor of 2.5 to account for the lower metallicity in the LMC are comparable to those found at the lower end of the range in Galactic hot cores. Our results have important implications for studies of organic chemistry at higher redshift.

  20. How to Commission, Operate and Maintain a Large Future Accelerator Complex From Far Remote Sites

    Energy Technology Data Exchange (ETDEWEB)

    Phinney, Nan

    2001-12-07

    A study on future large accelerators [1] has considered a facility, which is designed, built and operated by a worldwide collaboration of equal partner institutions, and which is remote from most of these institutions. The full range of operation was considered including commissioning, machine development, maintenance, troubleshooting and repair. Experience from existing accelerators confirms that most of these activities are already performed 'remotely'. The large high-energy physics experiments and astronomy projects, already involve international collaborations of distant institutions. Based on this experience, the prospects for a machine operated remotely from far sites are encouraging. Experts from each laboratory would remain at their home institution but continue to participate in the operation of the machine after construction. Experts are required to be on site only during initial commissioning and for particularly difficult problems. Repairs require an on-site non-expert maintenance crew. Most of the interventions can be made without an expert and many of the rest resolved with remote assistance. There appears to be no technical obstacle to controlling an accelerator from a distance. The major challenge is to solve the complex management and communication problems.

  1. THE GOULD's BELT VERY LARGE ARRAY SURVEY. I. THE OPHIUCHUS COMPLEX

    International Nuclear Information System (INIS)

    Dzib, Sergio A.; Loinard, Laurent; Rodríguez, Luis F.; Ortiz-León, Gisela N.; Pech, Gerardo; Rivera, Juana L.; Mioduszewski, Amy J.; Torres, Rosa M.; Boden, Andrew F.; Hartmann, Lee; Evans, Neal J. II; Briceño, Cesar; Tobin, John

    2013-01-01

    We present large-scale (∼2000 arcmin 2 ), deep (∼20 μJy), high-resolution (∼1'') radio observations of the Ophiuchus star-forming complex obtained with the Karl G. Jansky Very Large Array at λ = 4 and 6 cm. In total, 189 sources were detected, 56 of them associated with known young stellar sources, and 4 with known extragalactic objects; the other 129 remain unclassified, but most of them are most probably background quasars. The vast majority of the young stars detected at radio wavelengths have spectral types K or M, although we also detect four objects of A/F/B types and two brown dwarf candidates. At least half of these young stars are non-thermal (gyrosynchrotron) sources, with active coronas characterized by high levels of variability, negative spectral indices, and (in some cases) significant circular polarization. As expected, there is a clear tendency for the fraction of non-thermal sources to increase from the younger (Class 0/I or flat spectrum) to the more evolved (Class III or weak line T Tauri) stars. The young stars detected both in X-rays and at radio wavelengths broadly follow a Güdel-Benz relation, but with a different normalization than the most radioactive types of stars. Finally, we detect a ∼70 mJy compact extragalactic source near the center of the Ophiuchus core, which should be used as gain calibrator for any future radio observations of this region

  2. THE GOULD's BELT VERY LARGE ARRAY SURVEY. I. THE OPHIUCHUS COMPLEX

    Energy Technology Data Exchange (ETDEWEB)

    Dzib, Sergio A.; Loinard, Laurent; Rodríguez, Luis F.; Ortiz-León, Gisela N.; Pech, Gerardo; Rivera, Juana L. [Centro de Radioastronomía y Astrofísica, Universidad Nacional Autónoma de México Apartado Postal 3-72, 58090 Morelia, Michoacán (Mexico); Mioduszewski, Amy J. [National Radio Astronomy Observatory, Domenici Science Operations Center, 1003 Lopezville Road, Socorro, NM 87801 (United States); Torres, Rosa M. [Paul Harris 9065, Las Condes, Santiago (Chile); Boden, Andrew F. [Division of Physics, Math, and Astronomy, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125 (United States); Hartmann, Lee [Department of Astronomy, University of Michigan, 500 Church Street, Ann Arbor, MI 48105 (United States); Evans, Neal J. II [Department of Astronomy, The University of Texas at Austin, 1 University Station, C1400, Austin, TX 78712 (United States); Briceño, Cesar [Centro de Investigaciones de Astronomía, Mérida 5101-A (Venezuela, Bolivarian Republic of); Tobin, John, E-mail: s.dzib@crya.unam.mx [National Radio Astronomy Observatory, Charlottesville, VA 22903 (United States)

    2013-09-20

    We present large-scale (∼2000 arcmin{sup 2}), deep (∼20 μJy), high-resolution (∼1'') radio observations of the Ophiuchus star-forming complex obtained with the Karl G. Jansky Very Large Array at λ = 4 and 6 cm. In total, 189 sources were detected, 56 of them associated with known young stellar sources, and 4 with known extragalactic objects; the other 129 remain unclassified, but most of them are most probably background quasars. The vast majority of the young stars detected at radio wavelengths have spectral types K or M, although we also detect four objects of A/F/B types and two brown dwarf candidates. At least half of these young stars are non-thermal (gyrosynchrotron) sources, with active coronas characterized by high levels of variability, negative spectral indices, and (in some cases) significant circular polarization. As expected, there is a clear tendency for the fraction of non-thermal sources to increase from the younger (Class 0/I or flat spectrum) to the more evolved (Class III or weak line T Tauri) stars. The young stars detected both in X-rays and at radio wavelengths broadly follow a Güdel-Benz relation, but with a different normalization than the most radioactive types of stars. Finally, we detect a ∼70 mJy compact extragalactic source near the center of the Ophiuchus core, which should be used as gain calibrator for any future radio observations of this region.

  3. n-Order and maximum fuzzy similarity entropy for discrimination of signals of different complexity: Application to fetal heart rate signals.

    Science.gov (United States)

    Zaylaa, Amira; Oudjemia, Souad; Charara, Jamal; Girault, Jean-Marc

    2015-09-01

    This paper presents two new concepts for discrimination of signals of different complexity. The first focused initially on solving the problem of setting entropy descriptors by varying the pattern size instead of the tolerance. This led to the search for the optimal pattern size that maximized the similarity entropy. The second paradigm was based on the n-order similarity entropy that encompasses the 1-order similarity entropy. To improve the statistical stability, n-order fuzzy similarity entropy was proposed. Fractional Brownian motion was simulated to validate the different methods proposed, and fetal heart rate signals were used to discriminate normal from abnormal fetuses. In all cases, it was found that it was possible to discriminate time series of different complexity such as fractional Brownian motion and fetal heart rate signals. The best levels of performance in terms of sensitivity (90%) and specificity (90%) were obtained with the n-order fuzzy similarity entropy. However, it was shown that the optimal pattern size and the maximum similarity measurement were related to intrinsic features of the time series. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Trafficking of plant plasma membrane aquaporins: multiple regulation levels and complex sorting signals.

    Science.gov (United States)

    Chevalier, Adrien S; Chaumont, François

    2015-05-01

    Aquaporins are small channel proteins which facilitate the diffusion of water and small neutral molecules across biological membranes. Compared with animals, plant genomes encode numerous aquaporins, which display a large variety of subcellular localization patterns. More specifically, plant aquaporins of the plasma membrane intrinsic protein (PIP) subfamily were first described as plasma membrane (PM)-resident proteins, but recent research has demonstrated that the trafficking and subcellular localization of these proteins are complex and highly regulated. In the past few years, PIPs emerged as new model proteins to study subcellular sorting and membrane dynamics in plant cells. At least two distinct sorting motifs (one cytosolic, the other buried in the membrane) are required to direct PIPs to the PM. Hetero-oligomerization and interaction with SNAREs (soluble N-ethylmaleimide-sensitive factor protein attachment protein receptors) also influence the subcellular trafficking of PIPs. In addition to these constitutive processes, both the progression of PIPs through the secretory pathway and their dynamics at the PM are responsive to changing environmental conditions. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. Hsp90α forms a stable complex at the cilium neck for the interaction of signalling molecules in IGF-1 receptor signalling.

    Science.gov (United States)

    Wang, Hongzhong; Zou, Xinle; Wei, Zhuang; Wu, Yuan; Li, Rongxia; Zeng, Rong; Chen, Zhengjun; Liao, Kan

    2015-01-01

    The primary cilium is composed of an axoneme that protrudes from the cell surface, a basal body beneath the membrane and a transition neck in between. It is a sensory organelle on the plasma membrane, involved in mediating extracellular signals. In the transition neck region of the cilium, the microtubules change from triplet to doublet microtubules. This region also contains the transition fibres that crosslink the axoneme with the membrane and the necklace proteins that regulate molecules being transported into and out of the cilium. In this protein-enriched, complex area it is important to maintain the correct assembly of all of these proteins. Here, through immunofluorescent staining and protein isolation, we identify the molecular chaperone Hsp90α clustered at the periciliary base. At the transition neck region, phosphorylated Hsp90α forms a stable ring around the axoneme. Heat shock treatment causes Hsp90α to dissipate and induces resorption of cilia. We further identify that Hsp90α at the transition neck region represents a signalling platform on which IRS-1 interacts with intracellular downstream signalling molecules involved in IGF-1 receptor signalling. © 2015. Published by The Company of Biologists Ltd.

  6. Low complexity iterative MLSE equalization of M-QAM signals in extremely long rayleigh fading channels

    CSIR Research Space (South Africa)

    Myburgh, HC

    2009-05-01

    Full Text Available long channels. Its computational complexity is linear in the data block length and approximately independent of the channel memory length, whereas conventional equalization algorithms have computational complexity linear in the data block length...

  7. From PII signaling to metabolite sensing: a novel 2-oxoglutarate sensor that details PII-NAGK complex formation.

    Directory of Open Access Journals (Sweden)

    Jan Lüddecke

    Full Text Available The widespread PII signal transduction proteins are known for integrating signals of nitrogen and energy supply and regulating cellular behavior by interacting with a multitude of target proteins. The PII protein of the cyanobacterium Synechococcus elongatus forms complexes with the controlling enzyme of arginine synthesis, N-acetyl-L-glutamate kinase (NAGK in a 2-oxoglutarate- and ATP/ADP-dependent manner. Fusing NAGK and PII proteins to either CFP or YFP yielded a FRET sensor that specifically responded to 2-oxoglutarate. The impact of the fluorescent tags on PII and NAGK was evaluated by enzyme assays, surface plasmon resonance spectroscopy and isothermal calorimetric experiments. The developed FRET sensor provides real-time data on PII - NAGK interaction and its modulation by the effector molecules ATP, ADP and 2-oxoglutarate in vitro. Additionally to its utility to monitor 2-oxoglutarate levels, the FRET assay provided novel insights into PII - NAGK complex formation: (i It revealed the formation of an encounter-complex between PII and NAGK, which holds the proteins in proximity even in the presence of inhibitors of complex formation; (ii It revealed that the PII T-loop residue Ser49 is neither essential for complex formation with NAGK nor for activation of the enzyme but necessary to form a stable complex and efficiently relieve NAGK from arginine inhibition; (iii It showed that arginine stabilizes the NAGK hexamer and stimulates PII - NAGK interaction.

  8. ALGORITHM OF CARDIO COMPLEX DETECTION AND SORTING FOR PROCESSING THE DATA OF CONTINUOUS CARDIO SIGNAL MONITORING.

    Science.gov (United States)

    Krasichkov, A S; Grigoriev, E B; Nifontov, E M; Shapovalov, V V

    The paper presents an algorithm of cardio complex classification as part of processing the data of continuous cardiac monitoring. R-wave detection concurrently with cardio complex sorting is discussed. The core of this approach is the use of prior information about. cardio complex forms, segmental structure, and degree of kindness. Results of the sorting algorithm testing are provided.

  9. Signal transmission techniques for large-scale nuclear fuel reprocessing applications

    International Nuclear Information System (INIS)

    Herndon, J.N.; Bible, D.W.

    1985-01-01

    The RCE is currently developing a prototypic microwave-based signal transmission system for reprocessing cell applications. This system, being developed for use in the Advanced Integrated Maintenance System (AIMS), will operate in the 10-GHz frequency range. Provisions are being made for five real-time video channels, three bidirectional data channels at one megabaud data rate each, and two audio channels. The basic utility of the concept has been proven in a laboratory demonstration using gallium arsenide gunn diode transmitter/receivers with horn antennas. Unidirectional transmission of one real-time video channel over a distance of 200 ft was demonstrated. No evidence of multipath interference was detected even when the transmission path was surrounded by metallic reflectors. The microwave signal transmission system for the AIMS application is in final design. Fabrication in the ORNL instrument shops will begin in October 1985, and the system should be operational in the Maintenance Systems Test Area (MSTA) at ORNL in the latter half of 1986

  10. Independent signalling cues underpin arbuscular mycorrhizal symbiosis and large lateral root induction in rice.

    Science.gov (United States)

    Chiu, Chai Hao; Choi, Jeongmin; Paszkowski, Uta

    2018-01-01

    Perception of arbuscular mycorrhizal fungi (AMF) triggers distinct plant signalling responses for parallel establishment of symbiosis and induction of lateral root formation. Rice receptor kinase CHITIN ELICITOR RECEPTOR KINASE 1 (CERK1) and α/β-fold hydrolase DWARF14-LIKE (D14L) are involved in pre-symbiotic fungal perception. After 6 wk post-inoculation with Rhizophagus irregularis, root developmental responses, fungal colonization and transcriptional responses were monitored in two independent cerk1 null mutants; a deletion mutant lacking D14L, and with D14L complemented as well as their respective wild-type cultivars (cv Nipponbare and Nihonmasari). Here we show that although essential for symbiosis, D14L is dispensable for AMF-induced root architectural modulation, which conversely relies on CERK1. Our results demonstrate uncoupling of symbiosis and the symbiotic root developmental signalling during pre-symbiosis with CERK1 required for AMF-induced root architectural changes. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  11. World, We Have Problems: Simulation for Large Complex, Risky Projects, and Events

    Science.gov (United States)

    Elfrey, Priscilla

    2010-01-01

    Prior to a spacewalk during the NASA STS/129 mission in November 2009, Columbia Broadcasting System (CBS) correspondent William Harwood reported astronauts, "were awakened again", as they had been the day previously. Fearing something not properly connected was causing a leak, the crew, both on the ground and in space, stopped and checked everything. The alarm proved false. The crew did complete its work ahead of schedule, but the incident reminds us that correctly connecting hundreds and thousands of entities, subsystems and systems, finding leaks, loosening stuck valves, and adding replacements to very large complex systems over time does not occur magically. Everywhere major projects present similar pressures. Lives are at - risk. Responsibility is heavy. Large natural and human-created disasters introduce parallel difficulties as people work across boundaries their countries, disciplines, languages, and cultures with known immediate dangers as well as the unexpected. NASA has long accepted that when humans have to go where humans cannot go that simulation is the sole solution. The Agency uses simulation to achieve consensus, reduce ambiguity and uncertainty, understand problems, make decisions, support design, do planning and troubleshooting, as well as for operations, training, testing, and evaluation. Simulation is at the heart of all such complex systems, products, projects, programs, and events. Difficult, hazardous short and, especially, long-term activities have a persistent need for simulation from the first insight into a possibly workable idea or answer until the final report perhaps beyond our lifetime is put in the archive. With simulation we create a common mental model, try-out breakdowns of machinery or teamwork, and find opportunity for improvement. Lifecycle simulation proves to be increasingly important as risks and consequences intensify. Across the world, disasters are increasing. We anticipate more of them, as the results of global warming

  12. Examining Food Risk in the Large using a Complex, Networked System-of-sytems Approach

    Energy Technology Data Exchange (ETDEWEB)

    Ambrosiano, John [Los Alamos National Laboratory; Newkirk, Ryan [U OF MINNESOTA; Mc Donald, Mark P [VANDERBILT U

    2010-12-03

    The food production infrastructure is a highly complex system of systems. Characterizing the risks of intentional contamination in multi-ingredient manufactured foods is extremely challenging because the risks depend on the vulnerabilities of food processing facilities and on the intricacies of the supply-distribution networks that link them. A pure engineering approach to modeling the system is impractical because of the overall system complexity and paucity of data. A methodology is needed to assess food contamination risk 'in the large', based on current, high-level information about manufacturing facilities, corrunodities and markets, that will indicate which food categories are most at risk of intentional contamination and warrant deeper analysis. The approach begins by decomposing the system for producing a multi-ingredient food into instances of two subsystem archetypes: (1) the relevant manufacturing and processing facilities, and (2) the networked corrunodity flows that link them to each other and consumers. Ingredient manufacturing subsystems are modeled as generic systems dynamics models with distributions of key parameters that span the configurations of real facilities. Networks representing the distribution systems are synthesized from general information about food corrunodities. This is done in a series of steps. First, probability networks representing the aggregated flows of food from manufacturers to wholesalers, retailers, other manufacturers, and direct consumers are inferred from high-level approximate information. This is followed by disaggregation of the general flows into flows connecting 'large' and 'small' categories of manufacturers, wholesalers, retailers, and consumers. Optimization methods are then used to determine the most likely network flows consistent with given data. Vulnerability can be assessed for a potential contamination point using a modified CARVER + Shock model. Once the facility and

  13. Canonical TGF-β Signaling Negatively Regulates Neuronal Morphogenesis through TGIF/Smad Complex-Mediated CRMP2 Suppression.

    Science.gov (United States)

    Nakashima, Hideyuki; Tsujimura, Keita; Irie, Koichiro; Ishizu, Masataka; Pan, Miao; Kameda, Tomonori; Nakashima, Kinichi

    2018-05-16

    Functional neuronal connectivity requires proper neuronal morphogenesis and its dysregulation causes neurodevelopmental diseases. Transforming growth factor-β (TGF-β) family cytokines play pivotal roles in development, but little is known about their contribution to morphological development of neurons. Here we show that the Smad-dependent canonical signaling of TGF-β family cytokines negatively regulates neuronal morphogenesis during brain development. Mechanistically, activated Smads form a complex with transcriptional repressor TG-interacting factor (TGIF), and downregulate the expression of a neuronal polarity regulator, collapsin response mediator protein 2. We also demonstrate that TGF-β family signaling inhibits neurite elongation of human induced pluripotent stem cell-derived neurons. Furthermore, the expression of TGF-β receptor 1, Smad4, or TGIF, which have mutations found in patients with neurodevelopmental disorders, disrupted neuronal morphogenesis in both mouse (male and female) and human (female) neurons. Together, these findings suggest that the regulation of neuronal morphogenesis by an evolutionarily conserved function of TGF-β signaling is involved in the pathogenesis of neurodevelopmental diseases. SIGNIFICANCE STATEMENT Canonical transforming growth factor-β (TGF-β) signaling plays a crucial role in multiple organ development, including brain, and mutations in components of the signaling pathway associated with several human developmental disorders. In this study, we found that Smads/TG-interacting factor-dependent canonical TGF-β signaling regulates neuronal morphogenesis through the suppression of collapsin response mediator protein-2 (CRMP2) expression during brain development, and that function of this signaling is evolutionarily conserved in the mammalian brain. Mutations in canonical TGF-β signaling factors identified in patients with neurodevelopmental disorders disrupt the morphological development of neurons. Thus, our

  14. Large-Scale Transport Model Uncertainty and Sensitivity Analysis: Distributed Sources in Complex Hydrogeologic Systems

    International Nuclear Information System (INIS)

    Sig Drellack, Lance Prothro

    2007-01-01

    The Underground Test Area (UGTA) Project of the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office is in the process of assessing and developing regulatory decision options based on modeling predictions of contaminant transport from underground testing of nuclear weapons at the Nevada Test Site (NTS). The UGTA Project is attempting to develop an effective modeling strategy that addresses and quantifies multiple components of uncertainty including natural variability, parameter uncertainty, conceptual/model uncertainty, and decision uncertainty in translating model results into regulatory requirements. The modeling task presents multiple unique challenges to the hydrological sciences as a result of the complex fractured and faulted hydrostratigraphy, the distributed locations of sources, the suite of reactive and non-reactive radionuclides, and uncertainty in conceptual models. Characterization of the hydrogeologic system is difficult and expensive because of deep groundwater in the arid desert setting and the large spatial setting of the NTS. Therefore, conceptual model uncertainty is partially addressed through the development of multiple alternative conceptual models of the hydrostratigraphic framework and multiple alternative models of recharge and discharge. Uncertainty in boundary conditions is assessed through development of alternative groundwater fluxes through multiple simulations using the regional groundwater flow model. Calibration of alternative models to heads and measured or inferred fluxes has not proven to provide clear measures of model quality. Therefore, model screening by comparison to independently-derived natural geochemical mixing targets through cluster analysis has also been invoked to evaluate differences between alternative conceptual models. Advancing multiple alternative flow models, sensitivity of transport predictions to parameter uncertainty is assessed through Monte Carlo simulations. The

  15. Correlations between the signal complexity of cerebral and cardiac electrical activity: a multiscale entropy analysis.

    Directory of Open Access Journals (Sweden)

    Pei-Feng Lin

    Full Text Available The heart begins to beat before the brain is formed. Whether conventional hierarchical central commands sent by the brain to the heart alone explain all the interplay between these two organs should be reconsidered. Here, we demonstrate correlations between the signal complexity of brain and cardiac activity. Eighty-seven geriatric outpatients with healthy hearts and varied cognitive abilities each provided a 24-hour electrocardiography (ECG and a 19-channel eye-closed routine electroencephalography (EEG. Multiscale entropy (MSE analysis was applied to three epochs (resting-awake state, photic stimulation of fast frequencies (fast-PS, and photic stimulation of slow frequencies (slow-PS of EEG in the 1-58 Hz frequency range, and three RR interval (RRI time series (awake-state, sleep and that concomitant with the EEG for each subject. The low-to-high frequency power (LF/HF ratio of RRI was calculated to represent sympatho-vagal balance. With statistics after Bonferroni corrections, we found that: (a the summed MSE value on coarse scales of the awake RRI (scales 11-20, RRI-MSE-coarse were inversely correlated with the summed MSE value on coarse scales of the resting-awake EEG (scales 6-20, EEG-MSE-coarse at Fp2, C4, T6 and T4; (b the awake RRI-MSE-coarse was inversely correlated with the fast-PS EEG-MSE-coarse at O1, O2 and C4; (c the sleep RRI-MSE-coarse was inversely correlated with the slow-PS EEG-MSE-coarse at Fp2; (d the RRI-MSE-coarse and LF/HF ratio of the awake RRI were correlated positively to each other; (e the EEG-MSE-coarse at F8 was proportional to the cognitive test score; (f the results conform to the cholinergic hypothesis which states that cognitive impairment causes reduction in vagal cardiac modulation; (g fast-PS significantly lowered the EEG-MSE-coarse globally. Whether these heart-brain correlations could be fully explained by the central autonomic network is unknown and needs further exploration.

  16. Persistent activation of DNA damage signaling in response to complex mixtures of PAHs in air particulate matter

    Energy Technology Data Exchange (ETDEWEB)

    Jarvis, Ian W.H., E-mail: Ian.Jarvis@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden); Bergvall, Christoffer, E-mail: Christoffer.Bergvall@anchem.su.se [Department of Analytical Chemistry, Stockholm University, Svante Arrhenius väg 16, SE-106 91 Stockholm (Sweden); Bottai, Matteo, E-mail: Matteo.Bottai@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden); Westerholm, Roger, E-mail: Roger.Westerholm@anchem.su.se [Department of Analytical Chemistry, Stockholm University, Svante Arrhenius väg 16, SE-106 91 Stockholm (Sweden); Stenius, Ulla, E-mail: Ulla.Stenius@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden); Dreij, Kristian, E-mail: Kristian.Dreij@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden)

    2013-02-01

    Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are present in air particulate matter (PM) and have been associated with many adverse human health effects including cancer and respiratory disease. However, due to their complexity, the risk of exposure to mixtures is difficult to estimate. In the present study the effects of binary mixtures of benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) and complex mixtures of PAHs in urban air PM extracts on DNA damage signaling was investigated. Applying a statistical model to the data we observed a more than additive response for binary mixtures of BP and DBP on activation of DNA damage signaling. Persistent activation of checkpoint kinase 1 (Chk1) was observed at significantly lower BP equivalent concentrations in air PM extracts than BP alone. Activation of DNA damage signaling was also more persistent in air PM fractions containing PAHs with more than four aromatic rings suggesting larger PAHs contribute a greater risk to human health. Altogether our data suggests that human health risk assessment based on additivity such as toxicity equivalency factor scales may significantly underestimate the risk of exposure to complex mixtures of PAHs. The data confirms our previous findings with PAH-contaminated soil (Niziolek-Kierecka et al., 2012) and suggests a possible role for Chk1 Ser317 phosphorylation as a biological marker for future analyses of complex mixtures of PAHs. -- Highlights: ► Benzo[a]pyrene (BP), dibenzo[a,l]pyrene (DBP) and air PM PAH extracts were compared. ► Binary mixture of BP and DBP induced a more than additive DNA damage response. ► Air PM PAH extracts were more potent than toxicity equivalency factor estimates. ► Larger PAHs (> 4 rings) contribute more to the genotoxicity of PAHs in air PM. ► Chk1 is a sensitive marker for persistent activation of DNA damage signaling from PAH mixtures.

  17. Persistent activation of DNA damage signaling in response to complex mixtures of PAHs in air particulate matter

    International Nuclear Information System (INIS)

    Jarvis, Ian W.H.; Bergvall, Christoffer; Bottai, Matteo; Westerholm, Roger; Stenius, Ulla; Dreij, Kristian

    2013-01-01

    Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are present in air particulate matter (PM) and have been associated with many adverse human health effects including cancer and respiratory disease. However, due to their complexity, the risk of exposure to mixtures is difficult to estimate. In the present study the effects of binary mixtures of benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) and complex mixtures of PAHs in urban air PM extracts on DNA damage signaling was investigated. Applying a statistical model to the data we observed a more than additive response for binary mixtures of BP and DBP on activation of DNA damage signaling. Persistent activation of checkpoint kinase 1 (Chk1) was observed at significantly lower BP equivalent concentrations in air PM extracts than BP alone. Activation of DNA damage signaling was also more persistent in air PM fractions containing PAHs with more than four aromatic rings suggesting larger PAHs contribute a greater risk to human health. Altogether our data suggests that human health risk assessment based on additivity such as toxicity equivalency factor scales may significantly underestimate the risk of exposure to complex mixtures of PAHs. The data confirms our previous findings with PAH-contaminated soil (Niziolek-Kierecka et al., 2012) and suggests a possible role for Chk1 Ser317 phosphorylation as a biological marker for future analyses of complex mixtures of PAHs. -- Highlights: ► Benzo[a]pyrene (BP), dibenzo[a,l]pyrene (DBP) and air PM PAH extracts were compared. ► Binary mixture of BP and DBP induced a more than additive DNA damage response. ► Air PM PAH extracts were more potent than toxicity equivalency factor estimates. ► Larger PAHs (> 4 rings) contribute more to the genotoxicity of PAHs in air PM. ► Chk1 is a sensitive marker for persistent activation of DNA damage signaling from PAH mixtures.

  18. Magnetoelectric coupling study in multiferroic Pb(Fe0.5Nb0.5)O3 ceramics through small and large electric signal standard measurements

    International Nuclear Information System (INIS)

    Raymond, Oscar; Siqueiros, Jesus M.; Font, Reynaldo; Portelles, Jorge

    2011-01-01

    Multifunctional multiferroic materials such as the single phase compound Pb(Fe 0.5 Nb 0.5 )O 3 (PFN), where ferroelectric and antiferromagnetic order coexist, are very promising and have great interest from the academic and technological points of view. In this work, coupling of the ferroelectric and magnetic moments is reported. For this study, a combination of the small signal response using the impedance spectroscopy technique and the electromechanical resonance method with the large signal response through standard ferroelectric hysteresis measurement, has been used with and without an applied magnetic field. The measurements to determine the electrical properties of the ceramic were performed as functions of the bias and poling electric fields. A simultaneous analysis of the complex dielectric constant ε-tilde, impedance Z-tilde, electric modulus M-tilde, admittance Y-tilde, and the electromechanical parameters and coupling factors is presented. The results are correlated with a previous study of structural, morphological, small signal dielectric frequency-temperature response, and the ferroelectric hysteretic, magnetic and magnetodielectric behaviors. The observed shifts of the resonance and antiresonance frequency values can be associated with change of the ferroelectric domain size favored by the readjustment of the oxygen octahedron when the magnetic field is applied. From P-E hysteresis loops obtained without and with an external applied magnetic field, a dc magnetoelectric coupling effect with maximum value of 4 kV/cm T (400 mV/cm Oe) was obtained.

  19. Background Noises Versus Intraseasonal Variation Signals: Small vs. Large Convective Cloud Objects From CERES Aqua Observations

    Science.gov (United States)

    Xu, Kuan-Man

    2015-01-01

    During inactive phases of Madden-Julian Oscillation (MJO), there are plenty of deep but small convective systems and far fewer deep and large ones. During active phases of MJO, a manifestation of an increase in the occurrence of large and deep cloud clusters results from an amplification of large-scale motions by stronger convective heating. This study is designed to quantitatively examine the roles of small and large cloud clusters during the MJO life cycle. We analyze the cloud object data from Aqua CERES (Clouds and the Earth's Radiant Energy System) observations between July 2006 and June 2010 for tropical deep convective (DC) and cirrostratus (CS) cloud object types according to the real-time multivariate MJO index, which assigns the tropics to one of the eight MJO phases each day. The cloud object is a contiguous region of the earth with a single dominant cloud-system type. The criteria for defining these cloud types are overcast footprints and cloud top pressures less than 400 hPa, but DC has higher cloud optical depths (=10) than those of CS (background noises resulting from various types of the tropical waves with different wavenumbers and propagation speeds/directions.

  20. A large-signal dynamic simulation for the series resonant converter

    Science.gov (United States)

    King, R. J.; Stuart, T. A.

    1983-01-01

    A simple nonlinear discrete-time dynamic model for the series resonant dc-dc converter is derived using approximations appropriate to most power converters. This model is useful for the dynamic simulation of a series resonant converter using only a desktop calculator. The model is compared with a laboratory converter for a large transient event.

  1. Maize and Arabidopsis ARGOS Proteins Interact with Ethylene Receptor Signaling Complex, Supporting a Regulatory Role for ARGOS in Ethylene Signal Transduction[OPEN

    Science.gov (United States)

    Shi, Jinrui; Wang, Hongyu; Habben, Jeffrey E.

    2016-01-01

    The phytohormone ethylene regulates plant growth and development as well as plant response to environmental cues. ARGOS genes reduce plant sensitivity to ethylene when overexpressed in transgenic Arabidopsis (Arabidopsis thaliana) and maize (Zea mays). A previous genetic study suggested that the endoplasmic reticulum and Golgi-localized maize ARGOS1 targets the ethylene signal transduction components at or upstream of CONSTITUTIVE TRIPLE RESPONSE1, but the mechanism of ARGOS modulating ethylene signaling is unknown. Here, we demonstrate in Arabidopsis that ZmARGOS1, as well as the Arabidopsis ARGOS homolog ORGAN SIZE RELATED1, physically interacts with Arabidopsis REVERSION-TO-ETHYLENE SENSITIVITY1 (RTE1), an ethylene receptor interacting protein that regulates the activity of ETHYLENE RESPONSE1. The protein-protein interaction was also detected with the yeast split-ubiquitin two-hybrid system. Using the same yeast assay, we found that maize RTE1 homolog REVERSION-TO-ETHYLENE SENSITIVITY1 LIKE4 (ZmRTL4) and ZmRTL2 also interact with maize and Arabidopsis ARGOS proteins. Like AtRTE1 in Arabidopsis, ZmRTL4 and ZmRTL2 reduce ethylene responses when overexpressed in maize, indicating a similar mechanism for ARGOS regulating ethylene signaling in maize. A polypeptide fragment derived from ZmARGOS8, consisting of a Pro-rich motif flanked by two transmembrane helices that are conserved among members of the ARGOS family, can interact with AtRTE1 and maize RTL proteins in Arabidopsis. The conserved domain is necessary and sufficient to reduce ethylene sensitivity in Arabidopsis and maize. Overall, these results suggest a physical association between ARGOS and the ethylene receptor signaling complex via AtRTE1 and maize RTL proteins, supporting a role for ARGOS in regulating ethylene perception and the early steps of signal transduction in Arabidopsis and maize. PMID:27268962

  2. Deciphering complex dynamics of water counteraction around secondary structural elements of allosteric protein complex: Case study of SAP-SLAM system in signal transduction cascade.

    Science.gov (United States)

    Samanta, Sudipta; Mukherjee, Sanchita

    2018-01-28

    The first hydration shell of a protein exhibits heterogeneous behavior owing to several attributes, majorly local polarity and structural flexibility as revealed by solvation dynamics of secondary structural elements. We attempt to recognize the change in complex water counteraction generated due to substantial alteration in flexibility during protein complex formation. The investigation is carried out with the signaling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, and interacting with SLAM-associated protein (SAP), composed of one SH2 domain. All atom molecular dynamics simulations are employed to the aqueous solutions of free SAP and SLAM-peptide bound SAP. We observed that water dynamics around different secondary structural elements became highly affected as well as nicely correlated with the SLAM-peptide induced change in structural rigidity obtained by thermodynamic quantification. A few instances of contradictory dynamic features of water to the change in structural flexibility are explained by means of occluded polar residues by the peptide. For βD, EFloop, and BGloop, both structural flexibility and solvent accessibility of the residues confirm the obvious contribution. Most importantly, we have quantified enhanced restriction in water dynamics around the second Fyn-binding site of the SAP due to SAP-SLAM complexation, even prior to the presence of Fyn. This observation leads to a novel argument that SLAM induced more restricted water molecules could offer more water entropic contribution during the subsequent Fyn binding and provide enhanced stability to the SAP-Fyn complex in the signaling cascade. Finally, SLAM induced water counteraction around the second binding site of the SAP sheds light on the allosteric property of the SAP, which becomes an integral part of the underlying signal transduction mechanism.

  3. Deciphering complex dynamics of water counteraction around secondary structural elements of allosteric protein complex: Case study of SAP-SLAM system in signal transduction cascade

    Science.gov (United States)

    Samanta, Sudipta; Mukherjee, Sanchita

    2018-01-01

    The first hydration shell of a protein exhibits heterogeneous behavior owing to several attributes, majorly local polarity and structural flexibility as revealed by solvation dynamics of secondary structural elements. We attempt to recognize the change in complex water counteraction generated due to substantial alteration in flexibility during protein complex formation. The investigation is carried out with the signaling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, and interacting with SLAM-associated protein (SAP), composed of one SH2 domain. All atom molecular dynamics simulations are employed to the aqueous solutions of free SAP and SLAM-peptide bound SAP. We observed that water dynamics around different secondary structural elements became highly affected as well as nicely correlated with the SLAM-peptide induced change in structural rigidity obtained by thermodynamic quantification. A few instances of contradictory dynamic features of water to the change in structural flexibility are explained by means of occluded polar residues by the peptide. For βD, EFloop, and BGloop, both structural flexibility and solvent accessibility of the residues confirm the obvious contribution. Most importantly, we have quantified enhanced restriction in water dynamics around the second Fyn-binding site of the SAP due to SAP-SLAM complexation, even prior to the presence of Fyn. This observation leads to a novel argument that SLAM induced more restricted water molecules could offer more water entropic contribution during the subsequent Fyn binding and provide enhanced stability to the SAP-Fyn complex in the signaling cascade. Finally, SLAM induced water counteraction around the second binding site of the SAP sheds light on the allosteric property of the SAP, which becomes an integral part of the underlying signal transduction mechanism.

  4. Facilitated assignment of large protein NMR signals with covariance sequential spectra using spectral derivatives.

    Science.gov (United States)

    Harden, Bradley J; Nichols, Scott R; Frueh, Dominique P

    2014-09-24

    Nuclear magnetic resonance (NMR) studies of larger proteins are hampered by difficulties in assigning NMR resonances. Human intervention is typically required to identify NMR signals in 3D spectra, and subsequent procedures depend on the accuracy of this so-called peak picking. We present a method that provides sequential connectivities through correlation maps constructed with covariance NMR, bypassing the need for preliminary peak picking. We introduce two novel techniques to minimize false correlations and merge the information from all original 3D spectra. First, we take spectral derivatives prior to performing covariance to emphasize coincident peak maxima. Second, we multiply covariance maps calculated with different 3D spectra to destroy erroneous sequential correlations. The maps are easy to use and can readily be generated from conventional triple-resonance experiments. Advantages of the method are demonstrated on a 37 kDa nonribosomal peptide synthetase domain subject to spectral overlap.

  5. A Linearized Large Signal Model of an LCL-Type Resonant Converter

    Directory of Open Access Journals (Sweden)

    Hong-Yu Li

    2015-03-01

    Full Text Available In this work, an LCL-type resonant dc/dc converter with a capacitive output filter is modeled in two stages. In the first high-frequency ac stage, all ac signals are decomposed into two orthogonal vectors in a synchronous rotating d–q frame using multi-frequency modeling. In the dc stage, all dc quantities are represented by their average values with average state-space modeling. A nonlinear two-stage model is then created by means of a non-linear link. By aligning the transformer voltage on the d-axis, the nonlinear link can be eliminated, and the whole converter can be modeled by a single set of linear state-space equations. Furthermore, a feedback control scheme can be formed according to the steady-state solutions. Simulation and experimental results have proven that the resulted model is good for fast simulation and state variable estimation.

  6. Investigating complex patterns of blocked intestinal artery blood pressure signals by empirical mode decomposition and linguistic analysis

    International Nuclear Information System (INIS)

    Yeh, J-R; Lin, T-Y; Shieh, J-S; Chen, Y; Huang, N E; Wu, Z; Peng, C-K

    2008-01-01

    In this investigation, surgical operations of blocked intestinal artery have been conducted on pigs to simulate the condition of acute mesenteric arterial occlusion. The empirical mode decomposition method and the algorithm of linguistic analysis were applied to verify the blood pressure signals in simulated situation. We assumed that there was some information hidden in the high-frequency part of the blood pressure signal when an intestinal artery is blocked. The empirical mode decomposition method (EMD) has been applied to decompose the intrinsic mode functions (IMF) from a complex time series. But, the end effects and phenomenon of intermittence damage the consistence of each IMF. Thus, we proposed the complementary ensemble empirical mode decomposition method (CEEMD) to solve the problems of end effects and the phenomenon of intermittence. The main wave of blood pressure signals can be reconstructed by the main components, identified by Monte Carlo verification, and removed from the original signal to derive a riding wave. Furthermore, the concept of linguistic analysis was applied to design the blocking index to verify the pattern of riding wave of blood pressure using the measurements of dissimilarity. Blocking index works well to identify the situation in which the sampled time series of blood pressure signal was recorded. Here, these two totally different algorithms are successfully integrated and the existence of the existence of information hidden in high-frequency part of blood pressure signal has been proven

  7. Investigating complex patterns of blocked intestinal artery blood pressure signals by empirical mode decomposition and linguistic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, J-R; Lin, T-Y; Shieh, J-S [Department of Mechanical Engineering, Yuan Ze University, 135 Far-East Road, Chung-Li, Taoyuan, Taiwan (China); Chen, Y [Far Eastern Memorial Hospital, Taiwan (China); Huang, N E [Research Center for Adaptive Data Analysis, National Central University, Taiwan (China); Wu, Z [Center for Ocean-Land-Atmosphere Studies (United States); Peng, C-K [Beth Israel Deaconess Medical Center, Harvard Medical School (United States)], E-mail: s939205@ mail.yzu.edu.tw

    2008-02-15

    In this investigation, surgical operations of blocked intestinal artery have been conducted on pigs to simulate the condition of acute mesenteric arterial occlusion. The empirical mode decomposition method and the algorithm of linguistic analysis were applied to verify the blood pressure signals in simulated situation. We assumed that there was some information hidden in the high-frequency part of the blood pressure signal when an intestinal artery is blocked. The empirical mode decomposition method (EMD) has been applied to decompose the intrinsic mode functions (IMF) from a complex time series. But, the end effects and phenomenon of intermittence damage the consistence of each IMF. Thus, we proposed the complementary ensemble empirical mode decomposition method (CEEMD) to solve the problems of end effects and the phenomenon of intermittence. The main wave of blood pressure signals can be reconstructed by the main components, identified by Monte Carlo verification, and removed from the original signal to derive a riding wave. Furthermore, the concept of linguistic analysis was applied to design the blocking index to verify the pattern of riding wave of blood pressure using the measurements of dissimilarity. Blocking index works well to identify the situation in which the sampled time series of blood pressure signal was recorded. Here, these two totally different algorithms are successfully integrated and the existence of the existence of information hidden in high-frequency part of blood pressure signal has been proven.

  8. THE GOULD'S BELT VERY LARGE ARRAY SURVEY. IV. THE TAURUS-AURIGA COMPLEX

    Energy Technology Data Exchange (ETDEWEB)

    Dzib, Sergio A. [Max Planck Institut für Radioastronomie, Auf dem Hügel 69, D-53121 Bonn (Germany); Loinard, Laurent; Rodríguez, Luis F.; Ortiz-León, Gisela N.; Pech, Gerardo; Rivera, Juana L. [Centro de Radioastronomía y Astrofísica, Universidad Nacional Autónoma de México Apartado Postal 3-72, 58090 Morelia, Michoacán (Mexico); Mioduszewski, Amy J. [National Radio Astronomy Observatory, Domenici Science Operations Center, 1003 Lopezville Road, Socorro, NM 87801 (United States); Kounkel, Marina A.; Hartmann, Lee [Department of Astronomy, University of Michigan, 500 Church Street, Ann Arbor, MI 48105 (United States); Torres, Rosa M. [Instituto de Astronomía y Meteorología, Universidad de Guadalajara, Avenida Vallarta No. 2602, Col. Arcos Vallarta, CP 44130 Guadalajara, Jalisco, México (Mexico); Boden, Andrew F. [Division of Physics, Math, and Astronomy, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125 (United States); Evans II, Neal J. [Department of Astronomy, The University of Texas at Austin, 1 University Station, C1400, Austin, TX 78712 (United States); Briceño, Cesar [Cerro Tololo Interamerican Observatory, Casilla 603, La Serena (Chile); Tobin, John, E-mail: sdzib@mpifr-bonn.mpg.de [Leiden Observatory, Leiden University, P.O. Box 9513, 2300 RA Leiden (Netherlands)

    2015-03-10

    We present a multi-epoch radio study of the Taurus-Auriga star-forming complex made with the Karl G. Jansky Very Large Array at frequencies of 4.5 GHz and 7.5 GHz. We detect a total of 610 sources, 59 of which are related to young stellar objects (YSOs) and 18 to field stars. The properties of 56% of the young stars are compatible with non-thermal radio emission. We also show that the radio emission of more evolved YSOs tends to be more non-thermal in origin and, in general, that their radio properties are compatible with those found in other star-forming regions. By comparing our results with previously reported X-ray observations, we notice that YSOs in Taurus-Auriga follow a Güdel-Benz relation with κ = 0.03, as we previously suggested for other regions of star formation. In general, YSOs in Taurus-Auriga and in all the previous studied regions seem to follow this relation with a dispersion of ∼1 dex. Finally, we propose that most of the remaining sources are related with extragalactic objects but provide a list of 46 unidentified radio sources whose radio properties are compatible with a YSO nature.

  9. THE GOULD'S BELT VERY LARGE ARRAY SURVEY. IV. THE TAURUS-AURIGA COMPLEX

    International Nuclear Information System (INIS)

    Dzib, Sergio A.; Loinard, Laurent; Rodríguez, Luis F.; Ortiz-León, Gisela N.; Pech, Gerardo; Rivera, Juana L.; Mioduszewski, Amy J.; Kounkel, Marina A.; Hartmann, Lee; Torres, Rosa M.; Boden, Andrew F.; Evans II, Neal J.; Briceño, Cesar; Tobin, John

    2015-01-01

    We present a multi-epoch radio study of the Taurus-Auriga star-forming complex made with the Karl G. Jansky Very Large Array at frequencies of 4.5 GHz and 7.5 GHz. We detect a total of 610 sources, 59 of which are related to young stellar objects (YSOs) and 18 to field stars. The properties of 56% of the young stars are compatible with non-thermal radio emission. We also show that the radio emission of more evolved YSOs tends to be more non-thermal in origin and, in general, that their radio properties are compatible with those found in other star-forming regions. By comparing our results with previously reported X-ray observations, we notice that YSOs in Taurus-Auriga follow a Güdel-Benz relation with κ = 0.03, as we previously suggested for other regions of star formation. In general, YSOs in Taurus-Auriga and in all the previous studied regions seem to follow this relation with a dispersion of ∼1 dex. Finally, we propose that most of the remaining sources are related with extragalactic objects but provide a list of 46 unidentified radio sources whose radio properties are compatible with a YSO nature

  10. DnaSAM: Software to perform neutrality testing for large datasets with complex null models.

    Science.gov (United States)

    Eckert, Andrew J; Liechty, John D; Tearse, Brandon R; Pande, Barnaly; Neale, David B

    2010-05-01

    Patterns of DNA sequence polymorphisms can be used to understand the processes of demography and adaptation within natural populations. High-throughput generation of DNA sequence data has historically been the bottleneck with respect to data processing and experimental inference. Advances in marker technologies have largely solved this problem. Currently, the limiting step is computational, with most molecular population genetic software allowing a gene-by-gene analysis through a graphical user interface. An easy-to-use analysis program that allows both high-throughput processing of multiple sequence alignments along with the flexibility to simulate data under complex demographic scenarios is currently lacking. We introduce a new program, named DnaSAM, which allows high-throughput estimation of DNA sequence diversity and neutrality statistics from experimental data along with the ability to test those statistics via Monte Carlo coalescent simulations. These simulations are conducted using the ms program, which is able to incorporate several genetic parameters (e.g. recombination) and demographic scenarios (e.g. population bottlenecks). The output is a set of diversity and neutrality statistics with associated probability values under a user-specified null model that are stored in easy to manipulate text file. © 2009 Blackwell Publishing Ltd.

  11. A Modified Differential Coherent Bit Synchronization Algorithm for BeiDou Weak Signals with Large Frequency Deviation.

    Science.gov (United States)

    Han, Zhifeng; Liu, Jianye; Li, Rongbing; Zeng, Qinghua; Wang, Yi

    2017-07-04

    BeiDou system navigation messages are modulated with a secondary NH (Neumann-Hoffman) code of 1 kbps, where frequent bit transitions limit the coherent integration time to 1 millisecond. Therefore, a bit synchronization algorithm is necessary to obtain bit edges and NH code phases. In order to realize bit synchronization for BeiDou weak signals with large frequency deviation, a bit synchronization algorithm based on differential coherent and maximum likelihood is proposed. Firstly, a differential coherent approach is used to remove the effect of frequency deviation, and the differential delay time is set to be a multiple of bit cycle to remove the influence of NH code. Secondly, the maximum likelihood function detection is used to improve the detection probability of weak signals. Finally, Monte Carlo simulations are conducted to analyze the detection performance of the proposed algorithm compared with a traditional algorithm under the CN0s of 20~40 dB-Hz and different frequency deviations. The results show that the proposed algorithm outperforms the traditional method with a frequency deviation of 50 Hz. This algorithm can remove the effect of BeiDou NH code effectively and weaken the influence of frequency deviation. To confirm the feasibility of the proposed algorithm, real data tests are conducted. The proposed algorithm is suitable for BeiDou weak signal bit synchronization with large frequency deviation.

  12. Preprotein import into chloroplasts via the Toc and Tic complexes is regulated by redox signals in Pisum sativum.

    Science.gov (United States)

    Stengel, Anna; Benz, J Philipp; Buchanan, Bob B; Soll, Jürgen; Bölter, Bettina

    2009-11-01

    The import of nuclear-encoded preproteins is necessary to maintain chloroplast function. The recognition and transfer of most precursor proteins across the chloroplast envelopes are facilitated by two membrane-inserted protein complexes, the translocons of the chloroplast outer and inner envelope (Toc and Tic complexes, respectively). Several signals have been invoked to regulate the import of preproteins. In our study, we were interested in redox-based import regulation mediated by two signals: regulation based on thiols and on the metabolic NADP+/NADPH ratio. We sought to identify the proteins participating in the regulation of these transport pathways and to characterize the preprotein subgroups whose import is redox-dependent. Our results provide evidence that the formation and reduction of disulfide bridges in the Toc receptors and Toc translocation channel have a strong influence on import yield of all tested preproteins that depend on the Toc complex for translocation. Furthermore, the metabolic NADP+/NADPH ratio influences not only the composition of the Tic complex, but also the import efficiency of most, but not all, preproteins tested. Thus, several Tic subcomplexes appear to participate in the translocation of different preprotein subgroups, and the redox-active components of these complexes likely play a role in regulating transport.

  13. Large-Area All-Textile Pressure Sensors for Monitoring Human Motion and Physiological Signals.

    Science.gov (United States)

    Liu, Mengmeng; Pu, Xiong; Jiang, Chunyan; Liu, Ting; Huang, Xin; Chen, Libo; Du, Chunhua; Sun, Jiangman; Hu, Weiguo; Wang, Zhong Lin

    2017-11-01

    Wearable pressure sensors, which can perceive and respond to environmental stimuli, are essential components of smart textiles. Here, large-area all-textile-based pressure-sensor arrays are successfully realized on common fabric substrates. The textile sensor unit achieves high sensitivity (14.4 kPa -1 ), low detection limit (2 Pa), fast response (≈24 ms), low power consumption (sensor is demonstrated to be able to recognize finger movement, hand gestures, acoustic vibrations, and real-time pulse wave. Furthermore, large-area sensor arrays are successfully fabricated on one textile substrate to spatially map tactile stimuli and can be directly incorporated into a fabric garment for stylish designs without sacrifice of comfort, suggesting great potential in smart textiles or wearable electronics. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Jet signals for low mass strings at the large hadron collider.

    Science.gov (United States)

    Anchordoqui, Luis A; Goldberg, Haim; Nawata, Satoshi; Taylor, Tomasz R

    2008-05-02

    The mass scale M{s} of superstring theory is an arbitrary parameter that can be as low as few TeVs if the Universe contains large extra dimensions. We propose a search for the effects of Regge excitations of fundamental strings at the CERN Large Hadron Collider (LHC), in the process pp-->gamma+jet. The underlying parton process is dominantly the single photon production in gluon fusion, gg-->gammag, with open string states propagating in intermediate channels. If the photon mixes with the gauge boson of the baryon number, which is a common feature of D-brane quivers, the amplitude appears already at the string disk level. It is completely determined by the mixing parameter-and it is otherwise model (compactification) independent. Even for relatively small mixing, 100 fb{-1} of LHC data could probe deviations from standard model physics, at a 5sigma significance, for M{s} as large as 3.3 TeV.

  15. Effect of harmonicity on the detection of a signal in a complex masker and on spatial release from masking.

    Directory of Open Access Journals (Sweden)

    Astrid Klinge

    Full Text Available The amount of masking of sounds from one source (signals by sounds from a competing source (maskers heavily depends on the sound characteristics of the masker and the signal and on their relative spatial location. Numerous studies investigated the ability to detect a signal in a speech or a noise masker or the effect of spatial separation of signal and masker on the amount of masking, but there is a lack of studies investigating the combined effects of many cues on the masking as is typical for natural listening situations. The current study using free-field listening systematically evaluates the combined effects of harmonicity and inharmonicity cues in multi-tone maskers and cues resulting from spatial separation of target signal and masker on the detection of a pure tone in a multi-tone or a noise masker. A linear binaural processing model was implemented to predict the masked thresholds in order to estimate whether the observed thresholds can be accounted for by energetic masking in the auditory periphery or whether other effects are involved. Thresholds were determined for combinations of two target frequencies (1 and 8 kHz, two spatial configurations (masker and target either co-located or spatially separated by 90 degrees azimuth, and five different masker types (four complex multi-tone stimuli, one noise masker. A spatial separation of target and masker resulted in a release from masking for all masker types. The amount of masking significantly depended on the masker type and frequency range. The various harmonic and inharmonic relations between target and masker or between components of the masker resulted in a complex pattern of increased or decreased masked thresholds in comparison to the predicted energetic masking. The results indicate that harmonicity cues affect the detectability of a tonal target in a complex masker.

  16. Entamoeba histolytica: a beta 1 integrin-like fibronectin receptor assembles a signaling complex similar to those of mammalian cells.

    Science.gov (United States)

    Flores-Robles, Donaciano; Rosales, Carlos; Rosales-Encina, José Luis; Talamás-Rohana, Patricia

    2003-01-01

    During tissue invasion, Entamoeba histolytica trophozoites interact with endothelial cells and extracellular matrix (ECM) proteins such as fibronectin (FN), collagen, and laminin. It has been demonstrated that trophozoites interact with FN through a beta1 integrin-like FN receptor (beta 1EhFNR), activating tyrosine kinases. In order to characterize the signaling process triggered by the amoebic receptor, activation, and association of tyrosine kinases and structural proteins were determined. As a result of FN binding by the beta 1EhFNR, the receptor itself, FAK, and paxillin were phosphorylated in tyrosine. Co-immunoprecipitation experiments showed that a multimolecular signaling complex was formed by the amoebic FN receptor, FAK, paxillin, and vinculin. These results strongly suggest that a signaling pathway, similar to the one used in mammalian cells, is activated when E. histolytica trophozoites adhere to FN.

  17. Applying Statistical and Complex Network Methods to Explore the Key Signaling Molecules of Acupuncture Regulating Neuroendocrine-Immune Network

    Directory of Open Access Journals (Sweden)

    Kuo Zhang

    2018-01-01

    Full Text Available The mechanisms of acupuncture are still unclear. In order to reveal the regulatory effect of manual acupuncture (MA on the neuroendocrine-immune (NEI network and identify the key signaling molecules during MA modulating NEI network, we used a rat complete Freund’s adjuvant (CFA model to observe the analgesic and anti-inflammatory effect of MA, and, what is more, we used statistical and complex network methods to analyze the data about the expression of 55 common signaling molecules of NEI network in ST36 (Zusanli acupoint, and serum and hind foot pad tissue. The results indicate that MA had significant analgesic, anti-inflammatory effects on CFA rats; the key signaling molecules may play a key role during MA regulating NEI network, but further research is needed.

  18. Signal Formation Processes in Micromegas Detectors and Quality Control for large size Detector Construction for the ATLAS New Small Wheel

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00387450; Rembser, Christoph

    2017-08-04

    The Micromegas technology is one of the most successful modern gaseous detector concepts and widely utilized in nuclear and particle physics experiments. Twenty years of R & D rendered the technology sufficiently mature to be selected as precision tracking detector for the New Small Wheel (NSW) upgrade of the ATLAS Muon spectrometer. This will be the first large scale application of Micromegas in one of the major LHC experiments. However, many of the fundamental microscopic processes in these gaseous detectors are still not fully understood and studies on several detector aspects, like the micromesh geometry, have never been addressed systematically. The studies on signal formation in Micromegas, presented in the first part of this thesis, focuses on the microscopic signal electron loss mechanisms and the amplification processes in electron gas interaction. Based on a detailed model of detector parameter dependencies, these processes are scrutinized in an iterating comparison between exper- imental result...

  19. CYLD Limits Lys63- and Met1-Linked Ubiquitin at Receptor Complexes to Regulate Innate Immune Signaling

    Directory of Open Access Journals (Sweden)

    Matous Hrdinka

    2016-03-01

    Full Text Available Innate immune signaling relies on the deposition of non-degradative polyubiquitin at receptor-signaling complexes, but how these ubiquitin modifications are regulated by deubiquitinases remains incompletely understood. Met1-linked ubiquitin (Met1-Ub is assembled by the linear ubiquitin assembly complex (LUBAC, and this is counteracted by the Met1-Ub-specific deubiquitinase OTULIN, which binds to the catalytic LUBAC subunit HOIP. In this study, we report that HOIP also interacts with the deubiquitinase CYLD but that CYLD does not regulate ubiquitination of LUBAC components. Instead, CYLD limits extension of Lys63-Ub and Met1-Ub conjugated to RIPK2 to restrict signaling and cytokine production. Accordingly, Met1-Ub and Lys63-Ub were individually required for productive NOD2 signaling. Our study thus suggests that LUBAC, through its associated deubiquitinases, coordinates the deposition of not only Met1-Ub but also Lys63-Ub to ensure an appropriate response to innate immune receptor activation.

  20. Evaluation of infrasound signals from the shuttle Atlantis using a large seismic network.

    Science.gov (United States)

    de Groot-Hedlin, Catherine D; Hedlin, Michael A H; Walker, Kristoffer T; Drob, Douglas P; Zumberge, Mark A

    2008-09-01

    Inclement weather in Florida forced the space shuttle "Atlantis" to land at Edwards Air Force Base in southern California on June 22, 2007, passing near three infrasound stations and several hundred seismic stations in northern Mexico, southern California, and Nevada. The high signal-to-noise ratio, broad receiver coverage, and Atlantis' positional information allow for the testing of infrasound propagation modeling capabilities through the atmosphere to regional distances. Shadow zones and arrival times are predicted by tracing rays that are launched at right angles to the conical shock front surrounding the shuttle through a standard climatological model as well as a global ground to space model. The predictions and observations compare favorably over much of the study area for both atmospheric specifications. To the east of the shuttle trajectory, there were no detections beyond the primary acoustic carpet. Infrasound energy was detected hundreds of kilometers to the west and northwest (NW) of the shuttle trajectory, consistent with the predictions of ducting due to the westward summer-time stratospheric jet. Both atmospheric models predict alternating regions of high and low ensonifications to the NW. However, infrasound energy was detected tens of kilometers beyond the predicted zones of ensonification, possibly due to uncertainties in stratospheric wind speeds.

  1. Conformational coupling between receptor and kinase binding sites through a conserved salt bridge in a signaling complex scaffold protein.

    Directory of Open Access Journals (Sweden)

    Davi R Ortega

    Full Text Available Bacterial chemotaxis is one of the best studied signal transduction pathways. CheW is a scaffold protein that mediates the association of the chemoreceptors and the CheA kinase in a ternary signaling complex. The effects of replacing conserved Arg62 of CheW with other residues suggested that the scaffold protein plays a more complex role than simply binding its partner proteins. Although R62A CheW had essentially the same affinity for chemoreceptors and CheA, cells expressing the mutant protein are impaired in chemotaxis. Using a combination of molecular dynamics simulations (MD, NMR spectroscopy, and circular dichroism (CD, we addressed the role of Arg62. Here we show that Arg62 forms a salt bridge with another highly conserved residue, Glu38. Although this interaction is unimportant for overall protein stability, it is essential to maintain the correct alignment of the chemoreceptor and kinase binding sites of CheW. Computational and experimental data suggest that the role of the salt bridge in maintaining the alignment of the two partner binding sites is fundamental to the function of the signaling complex but not to its assembly. We conclude that a key feature of CheW is to maintain the specific geometry between the two interaction sites required for its function as a scaffold.

  2. CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma

    DEFF Research Database (Denmark)

    Graversen, Jonas Heilskov; Madsen, Mette; Moestrup, Søren K

    2002-01-01

    as the endocytic receptor binding hemoglobin (Hb) in complex with the plasma protein haptoglobin (Hp). This specific receptor-ligand interaction leading to removal from plasma of the Hp-Hb complex-but not free Hp or Hb-now explains the depletion of circulating Hp in individuals with increased intravascular...

  3. Wing, tail, and vocal contributions to the complex acoustic signals of courting Calliope hummingbirds

    Directory of Open Access Journals (Sweden)

    Christopher James CLARK

    2011-04-01

    Full Text Available Multi-component signals contain multiple signal parts expressed in the same physical modality. One way to identify individual components is if they are produced by different physical mechanisms. Here, I studied the mechanisms generating acoustic signals in the courtship displays of the Calliope hummingbird Stellula calliope. Display dives consisted of three synchronized sound elements, a high-frequency tone (hft, a low frequency tone (lft, and atonal sound pulses (asp, which were then followed by a frequency-modulated fall. Manipulating any of the rectrices (tail-feathers of wild males impaired production of the lft and asp but not the hft or fall, which are apparently vocal. I tested the sound production capabilities of the rectrices in a wind tunnel. Single rectrices could generate the lft but not the asp, whereas multiple rectrices tested together produced sounds similar to the asp when they fluttered and collided with their neighbors percussively, representing a previously unknown mechanism of sound production. During the shuttle display, a trill is generated by the wings during pulses in which the wingbeat frequency is elevated to 95 Hz, 40% higher than the typical hovering wingbeat frequency. The Calliope hummingbird courtship displays include sounds produced by three independent mechanisms, and thus include a minimum of three acoustic signal components. These acoustic mechanisms have different constraints and thus potentially contain different messages. Producing multiple acoustic signals via multiple mechanisms may be a way to escape the constraints present in any single mechanism [Current Zoology 57 (2: 187–196, 2011].

  4. Regulation of neurite morphogenesis by interaction between R7 regulator of G protein signaling complexes and G protein subunit Gα13.

    Science.gov (United States)

    Scherer, Stephanie L; Cain, Matthew D; Kanai, Stanley M; Kaltenbronn, Kevin M; Blumer, Kendall J

    2017-06-16

    The R7 regulator of G protein signaling family (R7-RGS) critically regulates nervous system development and function. Mice lacking all R7-RGS subtypes exhibit diverse neurological phenotypes, and humans bearing mutations in the retinal R7-RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms heterotrimeric complexes with Gβ 5 and R7-RGS-binding protein (R7BP) that regulate G protein-coupled receptor signaling by accelerating deactivation of G i/o α-subunits, several neurological phenotypes of R7-RGS knock-out mice are not readily explained by dysregulated G i/o signaling. Accordingly, we used tandem affinity purification and LC-MS/MS to search for novel proteins that interact with R7-RGS heterotrimers in the mouse brain. Among several proteins detected, we focused on Gα 13 because it had not been linked to R7-RGS complexes before. Split-luciferase complementation assays indicated that Gα 13 in its active or inactive state interacts with R7-RGS heterotrimers containing any R7-RGS isoform. LARG (leukemia-associated Rho guanine nucleotide exchange factor (GEF)), PDZ-RhoGEF, and p115RhoGEF augmented interaction between activated Gα 13 and R7-RGS heterotrimers, indicating that these effector RhoGEFs can engage Gα 13 ·R7-RGS complexes. Because Gα 13 /R7-RGS interaction required R7BP, we analyzed phenotypes of neuronal cell lines expressing RGS7 and Gβ 5 with or without R7BP. We found that neurite retraction evoked by Gα 12/13 -dependent lysophosphatidic acid receptors was augmented in R7BP-expressing cells. R7BP expression blunted neurite formation evoked by serum starvation by signaling mechanisms involving Gα 12/13 but not Gα i/o These findings provide the first evidence that R7-RGS heterotrimers interact with Gα 13 to augment signaling pathways that regulate neurite morphogenesis. This mechanism expands the diversity of functions whereby R7-RGS complexes regulate critical aspects of nervous system development and function. © 2017 by

  5. the Preliminary Research Based on Seismic Signals Generated by Hutubi Transmitting Seismic Station with One Large-volume Airgun Array

    Science.gov (United States)

    Wang, Q.; Su, J.; Wei, Y.; Zhang, W.; Wang, H.; Wang, B.; Ji, Z.

    2017-12-01

    For studying the subsurface structure and its subtle changes, we built the Hutubi transmitting seismic station with one large-volume airgun array at one artificial water pool in the northern segment of Tianshan mountain, where earthquakes occurred frequently. The airgun array consists of six airguns with every airgun capacity of 2000in3, and the artificial water pool with the top diameter of 100m, bottom diameter of 20m and the depth of 18m.We started the regular excitation experiment with the large-volume airgun source every week since June, 2013. Using seismic signals geneated by the Hutubi airgun source, we made the preliminary research on the airgun source, waveform characteristics and the subsurface velocity changes in the northern Tiansh mountain. The results are as follows: The seismic signal exited by the airgun source is characteristic of low-frequency ,and the dominant frequency is in the range of 2 6Hz. The Hutubi transmitting seismic station can continuously generate long-distance detectable and highly repeatable signals, and the correlation coefficient of sigals is greater than 0.95; and the longest propagation distance arrives to 380km, in addition, the 5000-shot stacked sigal using the phase weighted stack technique can be identified in the station, which is about 1300km from the Hutubi transmitting seismic station. Hutubi large-volume airgun source is fitted to detect and monitor the regional-scale subsurface stress state. Applying correlation test method, we measured weak subsurface velocity changes in the northern Tianshan mountain, and found that the several stations, which are within 150km from the the Hutubi transmitting seismic station, appeared 0.1 0.2% relative velocity changes before the Hutubi MS6.2 earthquake on Dec.8, 2016.

  6. SV40 large T-p53 complex: evidence for the presence of two immunologically distinct forms of p53

    International Nuclear Information System (INIS)

    Milner, J.; Gamble, J.

    1985-01-01

    The transforming protein of SV40 is the large T antigen. Large T binds a cellular protein, p53, which is potentially oncogenic by virtue of its functional involvement in the control of cell proliferation. This raises the possibility that p53 may mediate, in part, the transforming function of SV40 large T. Two immunologically distinct forms of p53 have been identified in normal cells: the forms are cell-cycle dependent, one being restricted to nondividing cells (p53-Go) and the second to dividing cells (p53-G divided by). The authors have now dissociated and probed the multimeric complex of SV40 large T-p53 for the presence of immunologically distinct forms of p53. Here they present evidence for the presence of p53-Go and p53-G divided by complexed with SV40 large T

  7. Detection of large numbers of novel sequences in the metatranscriptomes of complex marine microbial communities.

    Science.gov (United States)

    Gilbert, Jack A; Field, Dawn; Huang, Ying; Edwards, Rob; Li, Weizhong; Gilna, Paul; Joint, Ian

    2008-08-22

    Sequencing the expressed genetic information of an ecosystem (metatranscriptome) can provide information about the response of organisms to varying environmental conditions. Until recently, metatranscriptomics has been limited to microarray technology and random cloning methodologies. The application of high-throughput sequencing technology is now enabling access to both known and previously unknown transcripts in natural communities. We present a study of a complex marine metatranscriptome obtained from random whole-community mRNA using the GS-FLX Pyrosequencing technology. Eight samples, four DNA and four mRNA, were processed from two time points in a controlled coastal ocean mesocosm study (Bergen, Norway) involving an induced phytoplankton bloom producing a total of 323,161,989 base pairs. Our study confirms the finding of the first published metatranscriptomic studies of marine and soil environments that metatranscriptomics targets highly expressed sequences which are frequently novel. Our alternative methodology increases the range of experimental options available for conducting such studies and is characterized by an exceptional enrichment of mRNA (99.92%) versus ribosomal RNA. Analysis of corresponding metagenomes confirms much higher levels of assembly in the metatranscriptomic samples and a far higher yield of large gene families with >100 members, approximately 91% of which were novel. This study provides further evidence that metatranscriptomic studies of natural microbial communities are not only feasible, but when paired with metagenomic data sets, offer an unprecedented opportunity to explore both structure and function of microbial communities--if we can overcome the challenges of elucidating the functions of so many never-seen-before gene families.

  8. Precise Temporal Profiling of Signaling Complexes in Primary Cells Using SWATH Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Etienne Caron

    2017-03-01

    Full Text Available Spatiotemporal organization of protein interactions in cell signaling is a fundamental process that drives cellular functions. Given differential protein expression across tissues and developmental stages, the architecture and dynamics of signaling interaction proteomes is, likely, highly context dependent. However, current interaction information has been almost exclusively obtained from transformed cells. In this study, we applied an advanced and robust workflow combining mouse genetics and affinity purification (AP-SWATH mass spectrometry to profile the dynamics of 53 high-confidence protein interactions in primary T cells, using the scaffold protein GRB2 as a model. The workflow also provided a sufficient level of robustness to pinpoint differential interaction dynamics between two similar, but functionally distinct, primary T cell populations. Altogether, we demonstrated that precise and reproducible quantitative measurements of protein interaction dynamics can be achieved in primary cells isolated from mammalian tissues, allowing resolution of the tissue-specific context of cell-signaling events.

  9. Large-signal modeling of multi-finger InP DHBT devices at millimeter-wave frequencies

    DEFF Research Database (Denmark)

    Johansen, Tom Keinicke; Midili, Virginio; Squartecchia, Michele

    2017-01-01

    A large-signal modeling approach has been developed for multi-finger devices fabricated in an Indium Phosphide (InP) Double Heterojunction Bipolar Transistor (DHBT) process. The approach utilizes unit-finger device models embedded in a multi-port parasitic network. The unit-finger model is based...... on an improved UCSD HBT model formulation avoiding an erroneous RciCbci transit-time contribution from the intrinsic collector region as found in other III-V based HBT models. The mutual heating between fingers is modeled by a thermal coupling network with parameters extracted from electro-thermal simulations...

  10. Performance of the front-end signal processing electronics for the drift chambers of the Stanford Large Detector

    International Nuclear Information System (INIS)

    Honma, A.; Haller, G.M.; Usher, T.; Shypit, R.

    1990-10-01

    This paper reports on the performance of the front-end analog and digital signal processing electronics for the drift chambers of the Stanford Large Detector (SLD) detector at the Stanford Linear Collider. The electronics mounted on printed circuit boards include up to 64 channels of transimpedance amplification, analog sampling, A/D conversion, and associated control circuitry. Measurements of the time resolution, gain, noise, linearity, crosstalk, and stability of the readout electronics are described and presented. The expected contribution of the electronics to the relevant drift chamber measurement resolutions (i.e., timing and charge division) is given

  11. The biology of skin wetness perception and its implications in manual function and for reproducing complex somatosensory signals in neuroprosthetics

    Science.gov (United States)

    Ackerley, Rochelle

    2017-01-01

    Our perception of skin wetness is generated readily, yet humans have no known receptor (hygroreceptor) to signal this directly. It is easy to imagine the sensation of water running over our hands or the feel of rain on our skin. The synthetic sensation of wetness is thought to be produced from a combination of specific skin thermal and tactile inputs, registered through thermoreceptors and mechanoreceptors, respectively. The present review explores how thermal and tactile afference from the periphery can generate the percept of wetness centrally. We propose that the main signals include information about skin cooling, signaled primarily by thinly myelinated thermoreceptors, and rapid changes in touch, through fast-conducting, myelinated mechanoreceptors. Potential central sites for integration of these signals, and thus the perception of skin wetness, include the primary and secondary somatosensory cortices and the insula cortex. The interactions underlying these processes can also be modeled to aid in understanding and engineering the mechanisms. Furthermore, we discuss the role that sensing wetness could play in precision grip and the dexterous manipulation of objects. We expand on these lines of inquiry to the application of the knowledge in designing and creating skin sensory feedback in prosthetics. The addition of real-time, complex sensory signals would mark a significant advance in the use and incorporation of prosthetic body parts for amputees in everyday life. PMID:28123008

  12. [Dinitrosyl iron complexes are endogenous signaling agents in animal and human cells and tissues (a hypothesis)].

    Science.gov (United States)

    Vanin, A F

    2004-01-01

    The hypothesis was advanced that dinitrosyl iron complexes generated in animal and human cells and tissues producing nitric oxide can function as endogenous universal regulators of biochemical and physiological processes. This function is realized by the ability of dinitrosyl iron complexes to act as donors of free nitric oxide molecules interacting with the heme groups of proteins, nitrosonium ions, or Fe+(NO+)2 interacting with the thiol groups of proteins. The effect of dinitrosyl iron complexes on the activity of some enzymes and the expression of the genome at the translation and transcription levels was considered.

  13. Temporal signal energy correction and low-complexity encoder feedback for lossy scalable video coding

    NARCIS (Netherlands)

    Loomans, M.J.H.; Koeleman, C.J.; With, de P.H.N.

    2010-01-01

    In this paper, we address two problems found in embedded implementations of Scalable Video Codecs (SVCs): the temporal signal energy distribution and frame-to-frame quality fluctuations. The unequal energy distribution between the low- and high-pass band with integer-based wavelets leads to

  14. Conceptualization of the Complex Outcomes of Sexual Abuse: A Signal Detection Analysis

    Science.gov (United States)

    Pechtel, Pia; Evans, Ian M.; Podd, John V.

    2011-01-01

    Eighty-five New Zealand based practitioners experienced in treating adults with a history of child sexual abuse participated in an online judgment study of child sexual abuse outcomes using signal detection theory methodology. Participants' level of sensitivity was assessed independent of their degree of response bias when discriminating (a) known…

  15. Signal-to-Noise ratio and design complexity based on Unified Loss ...

    African Journals Online (AJOL)

    Taguchi's quality loss function for larger-the-better performance characteristics uses a reciprocal transformation to compute quality loss. This paper suggests that reciprocal transformation unnecessarily complicates and may distort results. Examples of this distortion include the signal-to-noise ratio based on mean squared ...

  16. Cytoplasmic organelles determine complexity and specificity of calcium signalling in adrenal chromaffin cells

    Czech Academy of Sciences Publication Activity Database

    Garsia-Sancho, J.; Verkhratsky, Alexei

    2008-01-01

    Roč. 192, č. 2 (2008), s. 263-271 ISSN 1748-1708 Institutional research plan: CEZ:AV0Z50390512 Keywords : Ca2+ signalling * calcium microdomains * chromaffin cells Subject RIV: JE - Non-nuclear Energetics, Energy Consumption ; Use Impact factor: 2.455, year: 2008

  17. Large Signal Stabilization of Hybrid AC/DC Micro-Grids Using Nonlinear Robust Controller

    Directory of Open Access Journals (Sweden)

    Reza Pejmanfar

    2017-12-01

    Full Text Available This paper presents a robust nonlinear integrated controller to improve stability of hybrid AC/DC micro-grids under islanding mode. The proposed controller includes two independent controllers where each one is responsible to control one part of the system. First controller will improve the stability of input DC/DC converter. Using this controller, the voltage of DC bus is fully stabilized such that when a large disturbance occurs, its voltage will become constant without any significant dynamic. The necessity of DC bus regulation which has not been considered in previous studies, is imminent as it not only improves voltage stability of the micro-grid but also protects consumers which are directly connected to the DC bus, against voltage variations. Frequency stability of the micro-grid is provided by the second proposed controller which is applied to output DC/AC converter of the micro-grid. Adaptive method is used to make the controllers proposed in this paper, robust. Duty cycle of converters switches are adjusted such that voltage and frequency of the micro-grid are set on the desired value in minimum possible time under transient disturbances and uncertainty of the loads as well as micro-sources characteristics.

  18. Orphan receptor GPR179 forms macromolecular complexes with components of metabotropic signaling cascade in retina ON-bipolar neurons.

    Science.gov (United States)

    Orlandi, Cesare; Cao, Yan; Martemyanov, Kirill A

    2013-10-29

    In the mammalian retina, synaptic transmission between light-excited rod photoreceptors and downstream ON-bipolar neurons is indispensable for dim vision, and disruption of this process leads to congenital stationary night blindness in human patients. The ON-bipolar neurons use the metabotropic signaling cascade, initiated by the mGluR6 receptor, to generate depolarizing responses to light-induced changes in neurotransmitter glutamate release from the photoreceptor axonal terminals. Evidence for the identity of the components involved in transducing these signals is growing rapidly. Recently, the orphan receptor, GPR179, a member of the G protein-coupled receptor (GPCR) superfamily, has been shown to be indispensable for the synaptic responses of ON-bipolar cells. In our study, we investigated the interaction of GPR179 with principle components of the signal transduction cascade. We used immunoprecipitation and proximity ligation assays in transfected cells and native retinas to characterize the protein-protein interactions involving GPR179. The influence of cascade components on GPR179 localization was examined through immunohistochemical staining of the retinas from genetic mouse models. We demonstrated that, in mouse retinas, GPR179 forms physical complexes with the main components of the metabotropic cascade, recruiting mGluR6, TRPM1, and the RGS proteins. Elimination of mGluR6 or RGS proteins, but not TRPM1, detrimentally affects postsynaptic targeting or GPR179 expression. These observations suggest that the mGluR6 signaling cascade is scaffolded as a macromolecular complex in which the interactions between the components ensure the optimal spatiotemporal characteristics of signal transduction.

  19. Mono-jet, -photon and -Z signals of a supersymmetric (B−L) model at the Large Hadron Collider

    Energy Technology Data Exchange (ETDEWEB)

    Abdallah, W. [Center for Fundamental Physics, Zewail City of Science and Technology,6 October City, Giza (Egypt); Department of Mathematics, Faculty of Science, Cairo University,Giza (Egypt); Fiaschi, J. [School of Physics and Astronomy, University of Southampton,Highfield, Southampton (United Kingdom); Khalil, S. [Center for Fundamental Physics, Zewail City of Science and Technology,6 October City, Giza (Egypt); Moretti, S. [School of Physics and Astronomy, University of Southampton,Highfield, Southampton (United Kingdom)

    2016-02-23

    Search for invisible final states produced at the Large Hadron Collider (LHC) by new physics scenarios are normally carried out resorting to a variety of probes emerging from the initial state, in the form of single-jet, -photon and -Z boson signatures. These are particularly effective for models of Supersymmetry (SUSY) in presence of R-parity conservation, owing to the presence in their spectra of a stable neutralino as a Dark Matter (DM) candidate. We assume here as theoretical framework the Supersymmetric version of the (B−L) extension of the Standard Model (BLSSM), wherein a mediator for invisible decays can be the Z{sup ′} boson present in this scenario. The peculiarity of the signal is thus that the final state objects carry a very large (transverse) missing energy, since the Z{sup ′} is naturally massive and constrained by direct searches and Electro-Weak Precision Tests (EWPTs) to be at least in the TeV scale region. Under these circumstances the efficiency in accessing the invisible final state and rejecting the Standard Model (SM) background is very high. This somehow compensates the rather meagre production rates. Another special feature of this invisible BLSSM signal is its composition, which is often dominated by sneutrino decays (alongside the more traditional neutrino and neutralino modes). Sensitivity of the CERN machine to these two features can therefore help disentangling the BLSSM from more popular SUSY models. We assess in this analysis the scope of the LHC in establishing the aforementioned invisible signals through a sophisticated signal-to-background simulation carried out in presence of parton shower, hadronisation as well as detector effects. We find that significant sensitivity exists already after 300 fb{sup −1} during Run 2. We find that mono-jet events can be readily accessible at the LHC, so as to enable one to claim a prompt discovery, while mono-photon and -Z signals can be used as diagnostic tools of the underlying scenario.

  20. Investigations of anomalous gravity signals prior to 71 large earthquakes based on a 4-years long superconducting gravimeter records

    Directory of Open Access Journals (Sweden)

    Dijin Wang

    2017-09-01

    Full Text Available Using continuous 1-Hz sampling time-series recorded by a SG (superconducting gravimeter at Hsinchu station, Taiwan of China, we investigate the anomalous gravity signals prior to 71 large earthquakes with moment magnitude larger than 7.0 (Mw7.0 occurred between 1 Jan 2008 and 31 Dec 2011. We firstly evaluate the noise level of the SG records at Hsinchu (HS station in microseismic bands from 0.05 Hz to 0.1 Hz by computing the PSD (power spectral density of seismically quiet days selected based on the RMS of records. Based on the analysis of the noise level and the spectral features of the seismically quiet SG records at HS station, we detect AGSs (anomalous gravity signals prior to large earthquakes. We apply HHT (Hilbert-Huang transformation to establish the TFEP (time-frequency-energy paradigms and MS (marginal spectra of the SG data before the large earthquakes, and the characteristics of TFEP and MS of the SGs data during the typhoon event are also analyzed. By comparing the spectral characteristics of the SGs data during seismically quiet period, three types of AGSs are found; and the occurrence rate of AGSs before 71 earthquakes is given in terms of the cases with different epicenter distance and different focal depth. The statistical results show that 56.3% of all the examined large earthquakes were preceded by AGSs; and if we constrain the epicenter distance to be smaller than 3500 km and focal depth less than 300 km, 75.3% of the examined large earthquakes can be associated with the AGSs. Especially, we note that for all the large earthquakes occurred in the Eurasian plate in recent four years, the precursory AGSs can always be found in the SG data recorded at HS station. Our investigations suggest that the AGSs prior to large earthquakes may be related to focal depth, epicentre distance and location.

  1. Switch I-dependent allosteric signaling in a G-protein chaperone-B12 enzyme complex.

    Science.gov (United States)

    Campanello, Gregory C; Lofgren, Michael; Yokom, Adam L; Southworth, Daniel R; Banerjee, Ruma

    2017-10-27

    G-proteins regulate various processes ranging from DNA replication and protein synthesis to cytoskeletal dynamics and cofactor assimilation and serve as models for uncovering strategies deployed for allosteric signal transduction. MeaB is a multifunctional G-protein chaperone, which gates loading of the active 5'-deoxyadenosylcobalamin cofactor onto methylmalonyl-CoA mutase (MCM) and precludes loading of inactive cofactor forms. MeaB also safeguards MCM, which uses radical chemistry, against inactivation and rescues MCM inactivated during catalytic turnover by using the GTP-binding energy to offload inactive cofactor. The conserved switch I and II signaling motifs used by G-proteins are predicted to mediate allosteric regulation in response to nucleotide binding and hydrolysis in MeaB. Herein, we targeted conserved residues in the MeaB switch I motif to interrogate the function of this loop. Unexpectedly, the switch I mutations had only modest effects on GTP binding and on GTPase activity and did not perturb stability of the MCM-MeaB complex. However, these mutations disrupted multiple MeaB chaperone functions, including cofactor editing, loading, and offloading. Hence, although residues in the switch I motif are not essential for catalysis, they are important for allosteric regulation. Furthermore, single-particle EM analysis revealed, for the first time, the overall architecture of the MCM-MeaB complex, which exhibits a 2:1 stoichiometry. These EM studies also demonstrate that the complex exhibits considerable conformational flexibility. In conclusion, the switch I element does not significantly stabilize the MCM-MeaB complex or influence the affinity of MeaB for GTP but is required for transducing signals between MeaB and MCM. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Si/SiC-based DD hetero-structure IMPATTs as MM-wave power-source: a generalized large-signal analysis

    International Nuclear Information System (INIS)

    Mukherjee, Moumita; Tripathy, P. R.; Pati, S. P.

    2015-01-01

    A full-scale, self-consistent, non-linear, large-signal model of double-drift hetero-structure IMPATT diode with general doping profile is derived. This newly developed model, for the first time, has been used to analyze the large-signal characteristics of hexagonal SiC-based double-drift IMPATT diode. Considering the fabrication feasibility, the authors have studied the large-signal characteristics of Si/SiC-based hetero-structure devices. Under small-voltage modulation (∼ 2%, i.e. small-signal conditions) results are in good agreement with calculations done using a linearised small-signal model. The large-signal values of the diode's negative conductance (5 × 10 6 S/m 2 ), susceptance (10.4 × 10 7 S/m 2 ), average breakdown voltage (207.6 V), and power generating efficiency (15%, RF power: 25.0 W at 94 GHz) are obtained as a function of oscillation amplitude (50% of DC breakdown voltage) for a fixed average current density. The large-signal calculations exhibit power and efficiency saturation for large-signal (> 50%) voltage modulation and thereafter decrease gradually with further increasing voltage-modulation. This generalized large-signal formulation is applicable for all types of IMPATT structures with distributed and narrow avalanche zones. The simulator is made more realistic by incorporating the space-charge effects, realistic field and temperature dependent material parameters in Si and SiC. The electric field snap-shots and the large-signal impedance and admittance of the diode with current excitation are expressed in closed loop form. This study will act as a guide for researchers to fabricate a high-power Si/SiC-based IMPATT for possible application in high-power MM-wave communication systems. (paper)

  3. Feasibility study in the application of optical signal analysis to non-destructive testing of complex structures

    Science.gov (United States)

    Baker, B.; Brown, H.

    1974-01-01

    Advantages of the large time bandwidth product of optical processing are presented. Experiments were performed to study the feasibility of the use of optical spectral analysis for detection of flaws in structural elements excited by random noise. Photographic and electronic methods of comparison of complex spectra were developed. Limitations were explored, and suggestions for further work are offered.

  4. Large scale IRAM 30 m CO-observations in the giant molecular cloud complex W43

    Science.gov (United States)

    Carlhoff, P.; Nguyen Luong, Q.; Schilke, P.; Motte, F.; Schneider, N.; Beuther, H.; Bontemps, S.; Heitsch, F.; Hill, T.; Kramer, C.; Ossenkopf, V.; Schuller, F.; Simon, R.; Wyrowski, F.

    2013-12-01

    We aim to fully describe the distribution and location of dense molecular clouds in the giant molecular cloud complex W43. It was previously identified as one of the most massive star-forming regions in our Galaxy. To trace the moderately dense molecular clouds in the W43 region, we initiated W43-HERO, a large program using the IRAM 30 m telescope, which covers a wide dynamic range of scales from 0.3 to 140 pc. We obtained on-the-fly-maps in 13CO (2-1) and C18O (2-1) with a high spectral resolution of 0.1 km s-1 and a spatial resolution of 12''. These maps cover an area of ~1.5 square degrees and include the two main clouds of W43 and the lower density gas surrounding them. A comparison to Galactic models and previous distance calculations confirms the location of W43 near the tangential point of the Scutum arm at approximately 6 kpc from the Sun. The resulting intensity cubes of the observed region are separated into subcubes, which are centered on single clouds and then analyzed in detail. The optical depth, excitation temperature, and H2 column density maps are derived out of the 13CO and C18O data. These results are then compared to those derived from Herschel dust maps. The mass of a typical cloud is several 104 M⊙ while the total mass in the dense molecular gas (>102 cm-3) in W43 is found to be ~1.9 × 106 M⊙. Probability distribution functions obtained from column density maps derived from molecular line data and Herschel imaging show a log-normal distribution for low column densities and a power-law tail for high densities. A flatter slope for the molecular line data probability distribution function may imply that those selectively show the gravitationally collapsing gas. Appendices are available in electronic form at http://www.aanda.orgThe final datacubes (13CO and C18O) for the entire survey are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/560/A24

  5. Complex signal-based optical coherence tomography angiography enables in vivo visualization of choriocapillaris in human choroid

    Science.gov (United States)

    Chu, Zhongdi; Chen, Chieh-Li; Zhang, Qinqin; Pepple, Kathryn; Durbin, Mary; Gregori, Giovanni; Wang, Ruikang K.

    2017-12-01

    The choriocapillaris (CC) plays an essential role in maintaining the normal functions of the human eye. There is increasing interest in the community to develop an imaging technique for visualizing the CC, yet this remains underexplored due to technical limitations. We propose an approach for the visualization of the CC in humans via a complex signal-based optical microangiography (OMAG) algorithm, based on commercially available spectral domain optical coherence tomography (SD-OCT). We show that the complex signal-based OMAG was superior to both the phase and amplitude signal-based approaches in detailing the vascular lobules previously seen with histological analysis. With this improved ability to visualize the lobular vascular networks, it is possible to identify the feeding arterioles and draining venules around the lobules, which is important in understanding the role of the CC in the pathogenesis of ocular diseases. With built-in FastTrac™ and montage scanning capabilities, we also demonstrate wide-field SD-OCT angiograms of the CC with a field of view at 9×11 mm2.

  6. Influence of multi-microphone signal enhancement algorithms on auditory movement detection in acoustically complex situations

    DEFF Research Database (Denmark)

    Lundbeck, Micha; Hartog, Laura; Grimm, Giso

    2017-01-01

    The influence of hearing aid (HA) signal processing on the perception of spatially dynamic sounds has not been systematically investigated so far. Previously, we observed that interfering sounds impaired the detectability of left-right source movements and reverberation that of near-far source...... movements for elderly hearing-impaired (EHI) listeners (Lundbeck et al., 2017). Here, we explored potential ways of improving these deficits with HAs. To that end, we carried out acoustic analyses to examine the impact of two beamforming algorithms and a binaural coherence-based noise reduction scheme...... on the cues underlying movement perception. While binaural cues remained mostly unchanged, there were greater monaural spectral changes and increases in signal-to-noise ratio and direct-to-reverberant sound ratio as a result of the applied processing. Based on these findings, we conducted a listening test...

  7. Acoustic wave focusing in complex media using Nonlinear Time Reversal coded signal processing

    Czech Academy of Sciences Publication Activity Database

    Dos Santos, S.; Dvořáková, Zuzana; Lints, M.; Kůs, V.; Salupere, A.; Převorovský, Zdeněk

    2014-01-01

    Roč. 19, č. 12 (2014) ISSN 1435-4934. [European Conference on Non-Destructive Testing (ECNDT 2014) /11./. Praha, 06.10.2014-10.10.2014] Institutional support: RVO:61388998 Keywords : ultrasonic testing (UT) * signal processing * TR- NEWS * nonlinear time reversal * NDT * nonlinear acoustics Subject RIV: BI - Acoustics http://www.ndt.net/events/ECNDT2014/app/content/Slides/590_DosSantos_Rev1.pdf

  8. Abnormal Cell Properties and Down-Regulated FAK-Src Complex Signaling in B Lymphoblasts of Autistic Subjects

    Science.gov (United States)

    Wei, Hongen; Malik, Mazhar; Sheikh, Ashfaq M.; Merz, George; Ted Brown, W.; Li, Xiaohong

    2011-01-01

    Recent studies suggest that one of the major pathways to the pathogenesis of autism is reduced cell migration. Focal adhesion kinase (FAK) has an important role in neural migration, dendritic morphological characteristics, axonal branching, and synapse formation. The FAK-Src complex, activated by upstream reelin and integrin β1, can initiate a cascade of phosphorylation events to trigger multiple intracellular pathways, including mitogen-activated protein kinase–extracellular signal–regulated kinase and phosphatidylinositol 3-kinase–Akt signaling. In this study, by using B lymphoblasts as a model, we tested whether integrin β1 and FAK-Src signaling are abnormally regulated in autism and whether abnormal FAK-Src signaling leads to defects in B-lymphoblast adhesion, migration, proliferation, and IgG production. To our knowledge, for the first time, we show that protein expression levels of both integrin β1 and FAK are significantly decreased in autistic lymphoblasts and that Src protein expression and the phosphorylation of an active site (Y416) are also significantly decreased. We also found that lymphoblasts from autistic subjects exhibit significantly decreased migration, increased adhesion properties, and an impaired capacity for IgG production. The overexpression of FAK in autistic lymphoblasts countered the adhesion and migration defects. In addition, we demonstrate that FAK mediates its effect through the activation of Src, phosphatidylinositol 3-kinase–Akt, and mitogen-activated protein kinase signaling cascades and that paxillin is also likely involved in the regulation of adhesion and migration in autistic lymphoblasts. PMID:21703394

  9. Improving the arterial input function in dynamic contrast enhanced MRI by fitting the signal in the complex plane.

    Science.gov (United States)

    Simonis, Frank F J; Sbrizzi, Alessandro; Beld, Ellis; Lagendijk, Jan J W; van den Berg, Cornelis A T

    2016-10-01

    Dynamic contrast enhanced (DCE) imaging is a widely used technique in oncologic imaging. An essential prerequisite for obtaining quantitative values from DCE-MRI is the determination of the arterial input function (AIF). However, it is very challenging to accurately estimate the AIF using MR. A comprehensive model, which uses complex data instead of either magnitude or phase, was developed to improve AIF estimation. The model was first applied to simulated data. Subsequently, the accuracy of the estimated contrast agent concentration was validated in a phantom. Finally the method was applied to existing DCE scans of 13 prostate cancer patients. The complex signal method combines the complementary strengths of the magnitude and phase method, increasing the precision and accuracy of concentration estimation in simulated and phantom data. The in vivo AIFs show a good agreement between arterial voxels (standard deviation in the peak and tail equal 0.4 mM and 0.12 mM, respectively). Furthermore, the dynamic behavior closely followed the AIF obtained with DCE-CT in the same patients (mean correlation coefficient: 0.92). By using the complex signal, the AIF estimation becomes more accurate and precise. This might enable patient specific AIFs, thereby improving the quantitative values obtained from DCE-MRI. Magn Reson Med 76:1236-1245, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  10. High frequency seismic signal generated by landslides on complex topographies: from point source to spatially distributed sources

    Science.gov (United States)

    Mangeney, A.; Kuehnert, J.; Capdeville, Y.; Durand, V.; Stutzmann, E.; Kone, E. H.; Sethi, S.

    2017-12-01

    During their flow along the topography, landslides generate seismic waves in a wide frequency range. These so called landquakes can be recorded at very large distances (a few hundreds of km for large landslides). The recorded signals depend on the landslide seismic source and the seismic wave propagation. If the wave propagation is well understood, the seismic signals can be inverted for the seismic source and thus can be used to get information on the landslide properties and dynamics. Analysis and modeling of long period seismic signals (10-150s) have helped in this way to discriminate between different landslide scenarios and to constrain rheological parameters (e.g. Favreau et al., 2010). This was possible as topography poorly affects wave propagation at these long periods and the landslide seismic source can be approximated as a point source. In the near-field and at higher frequencies (> 1 Hz) the spatial extent of the source has to be taken into account and the influence of the topography on the recorded seismic signal should be quantified in order to extract information on the landslide properties and dynamics. The characteristic signature of distributed sources and varying topographies is studied as a function of frequency and recording distance.The time dependent spatial distribution of the forces applied to the ground by the landslide are obtained using granular flow numerical modeling on 3D topography. The generated seismic waves are simulated using the spectral element method. The simulated seismic signal is compared to observed seismic data from rockfalls at the Dolomieu Crater of Piton de la Fournaise (La Réunion).Favreau, P., Mangeney, A., Lucas, A., Crosta, G., and Bouchut, F. (2010). Numerical modeling of landquakes. Geophysical Research Letters, 37(15):1-5.

  11. Failure of large transformation projects from the viewpoint of complex adaptive systems: Management principles for dealing with project dynamics

    NARCIS (Netherlands)

    Janssen, M.; Voort, H. van der; Veenstra, A.F.E. van

    2015-01-01

    Many large transformation projects do not result in the outcomes desired or envisioned by the stakeholders. This type of project is characterised by dynamics which are both caused by and result of uncertainties and unexpected behaviour. In this paper a complex adaptive system (CAS) view was adopted

  12. Large-scale grid-enabled lattice-Boltzmann simulations of complex fluid flow in porous media and under shear

    NARCIS (Netherlands)

    Harting, J.D.R.; Venturoli, M.; Coveney, P.V.

    2004-01-01

    Well–designed lattice Boltzmann codes exploit the essentially embarrassingly parallel features of the algorithm and so can be run with considerable efficiency on modern supercomputers. Such scalable codes permit us to simulate the behaviour of increasingly large quantities of complex condensed

  13. Max-Min SINR in Large-Scale Single-Cell MU-MIMO: Asymptotic Analysis and Low Complexity Transceivers

    KAUST Repository

    Sifaou, Houssem; Kammoun, Abla; Sanguinetti, Luca; Debbah, Merouane; Alouini, Mohamed-Slim

    2016-01-01

    This work focuses on the downlink and uplink of large-scale single-cell MU-MIMO systems in which the base station (BS) endowed with M antennas communicates with K single-antenna user equipments (UEs). Particularly, we aim at reducing the complexity

  14. The challenge for genetic epidemiologists: how to analyze large numbers of SNPs in relation to complex diseases

    NARCIS (Netherlands)

    Heidema, A.G.; Boer, J.M.A.; Nagelkerke, N.; Mariman, E.C.M.; A, van der D.L.; Feskens, E.J.M.

    2006-01-01

    Genetic epidemiologists have taken the challenge to identify genetic polymorphisms involved in the development of diseases. Many have collected data on large numbers of genetic markers but are not familiar with available methods to assess their association with complex diseases. Statistical methods

  15. Price computation in electricity auctions with complex rules: An analysis of investment signals

    International Nuclear Information System (INIS)

    Vazquez, Carlos; Hallack, Michelle; Vazquez, Miguel

    2017-01-01

    This paper discusses the problem of defining marginal costs when integer variables are present, in the context of short-term power auctions. Most of the proposals for price computation existing in the literature are concerned with short-term competitive equilibrium (generators should not be willing to change the dispatch assigned to them by the auctioneer), which implies operational-cost recovery for all of the generators accepted in the auction. However, this is in general not enough to choose between the different pricing schemes. We propose to include an additional criterion in order to discriminate among different pricing schemes: prices have to be also signals for generation expansion. Using this condition, we arrive to a single solution to the problem of defining prices, where they are computed as the shadow prices of the balance equations in a linear version of the unit commitment problem. Importantly, not every linearization of the unit commitment is valid; we develop the conditions for this linear model to provide adequate investment signals. Compared to other proposals in the literature, our results provide a strong motivation for the pricing scheme and a simple method for price computation. - Highlights: • Pricing proposals in power markets often deal with just accounting-cost recovery. • Including opportunity costs is an additional property required for efficient pricing. • We develop a framework to analyze the pricing proposals found in the literature. • We propose a pricing mechanism to include the costs of short-run integer decisions. • As it includes short-run opportunity costs, it provides efficient long-term signals.

  16. Mislocalization of the MRN complex prevents ATR signaling during adenovirus infection

    DEFF Research Database (Denmark)

    Carson, Christian T; Orazio, Nicole I; Lee, Darwin V

    2009-01-01

    The protein kinases ataxia-telangiectasia mutated (ATM) and ATM-Rad3 related (ATR) are activated in response to DNA damage, genotoxic stress and virus infections. Here we show that during infection with wild-type adenovirus, ATR and its cofactors RPA32, ATRIP and TopBP1 accumulate at viral...... during virus infection, which is independent of Mre11 nuclease activity and recruitment of RPA/ATR/ATRIP/TopBP1. Unlike other damage scenarios, we found that ATM and ATR signaling are not dependent on each other during infection. We identify a region of the viral E4orf3 protein responsible...

  17. Rotation analysis on large complex superconducting cables based on numerical modeling and experiments

    NARCIS (Netherlands)

    Qin, Jinggang; Yue, Donghua; Zhang, Xingyi; Wu, Yu; Liu, Xiaochuan; Liu, Huajun; Jin, Huan; Dai, Chao; Nijhuis, Arend; Zhou, Chao; Devred, Arnaud

    2018-01-01

    The conductors used in large fusion reactors, e.g. ITER, CFETR and DEMO, are made of cable-in-conduit conductor (CICC) with large diameters up to about 50 mm. The superconducting and copper strands are cabled around a central spiral and then wrapped with stainless-steel tape of 0.1 mm thickness. The

  18. Low-Complexity Iterative Receiver for Space-Time Coded Signals over Frequency Selective Channels

    Directory of Open Access Journals (Sweden)

    Mohamed Siala

    2002-05-01

    Full Text Available We propose a low-complexity turbo-detector scheme for frequency selective multiple-input multiple-output channels. The detection part of the receiver is based on a List-type MAP equalizer which is a state-reduction algorithm of the MAP algorithm using per-survivor technique. This alternative achieves a good tradeoff between performance and complexity provided a small amount of the channel is neglected. In order to induce the good performance of this equalizer, we propose to use a whitened matched filter (WMF which leads to a white-noise “minimum phase” channel model. Simulation results show that the use of the WMF yields significant improvement, particularly over severe channels. Thanks to the iterative turbo processing (detection and decoding are iterated several times, the performance loss due to the use of the suboptimum List-type equalizer is recovered.

  19. Broad-Complex acts downstream of Met in juvenile hormone signaling to coordinate primitive holometabolan metamorphosis

    Czech Academy of Sciences Publication Activity Database

    Konopová, Barbora; Jindra, Marek

    2008-01-01

    Roč. 135, č. 3 (2008), s. 559-568 ISSN 0950-1991 R&D Projects: GA ČR(CZ) GA204/07/1032; GA AV ČR IAA5007305; GA MŠk LC07032 Institutional research plan: CEZ:AV0Z50070508 Keywords : metamorphosis * juvenile hormone * broad-complex Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.812, year: 2008

  20. Gold nanoparticle-mediated laser stimulation causes a complex stress signal in neuronal cells

    Science.gov (United States)

    Johannsmeier, Sonja; Heeger, Patrick; Terakawa, Mitsuhiro; Kalies, Stefan; Heisterkamp, Alexander; Ripken, Tammo; Heinemann, Dag

    2017-07-01

    Gold nanoparticle mediated laser stimulation of neuronal cells allows for cell activation on a single-cell level. It could therefore be considered an alternative to classical electric neurostimulation. The physiological impact of this new approach has not been intensively studied so far. Here, we investigate the targeted cell's reaction to a laser stimulus based on its calcium response. A complex cellular reaction involving multiple sources has been revealed.

  1. Mapping multivalency and differential affinities within large intrinsically disordered protein complexes with segmental motion analysis.

    Science.gov (United States)

    Milles, Sigrid; Lemke, Edward A

    2014-07-07

    Intrinsically disordered proteins (IDPs) can bind to multiple interaction partners. Numerous binding regions in the IDP that act in concert through complex cooperative effects facilitate such interactions, but complicate studying IDP complexes. To address this challenge we developed a combined fluorescence correlation and time-resolved polarization spectroscopy approach to study the binding properties of the IDP nucleoporin153 (Nup153) to nuclear transport receptors (NTRs). The detection of segmental backbone mobility of Nup153 within the unperturbed complex provided a readout of local, region-specific binding properties that are usually masked in measurements of the whole IDP. The binding affinities of functionally and structurally diverse NTRs to distinct regions of Nup153 can differ by orders of magnitudes-a result with implications for the diversity of transport routes in nucleocytoplasmic transport. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. The biology of skin wetness perception and its implications in manual function and for reproducing complex somatosensory signals in neuroprosthetics.

    Science.gov (United States)

    Filingeri, Davide; Ackerley, Rochelle

    2017-04-01

    Our perception of skin wetness is generated readily, yet humans have no known receptor (hygroreceptor) to signal this directly. It is easy to imagine the sensation of water running over our hands or the feel of rain on our skin. The synthetic sensation of wetness is thought to be produced from a combination of specific skin thermal and tactile inputs, registered through thermoreceptors and mechanoreceptors, respectively. The present review explores how thermal and tactile afference from the periphery can generate the percept of wetness centrally. We propose that the main signals include information about skin cooling, signaled primarily by thinly myelinated thermoreceptors, and rapid changes in touch, through fast-conducting, myelinated mechanoreceptors. Potential central sites for integration of these signals, and thus the perception of skin wetness, include the primary and secondary somatosensory cortices and the insula cortex. The interactions underlying these processes can also be modeled to aid in understanding and engineering the mechanisms. Furthermore, we discuss the role that sensing wetness could play in precision grip and the dexterous manipulation of objects. We expand on these lines of inquiry to the application of the knowledge in designing and creating skin sensory feedback in prosthetics. The addition of real-time, complex sensory signals would mark a significant advance in the use and incorporation of prosthetic body parts for amputees in everyday life. NEW & NOTEWORTHY Little is known about the underlying mechanisms that generate the perception of skin wetness. Humans have no specific hygroreceptor, and thus temperature and touch information combine to produce wetness sensations. The present review covers the potential mechanisms leading to the perception of wetness, both peripherally and centrally, along with their implications for manual function. These insights are relevant to inform the design of neuroengineering interfaces, such as sensory

  3. Development of a RF large signal MOSFET model, based on an equivalent circuit, and comparison with the BSIM3v3 compact model.

    NARCIS (Netherlands)

    Vandamme, E.P.; Schreurs, D.; Dinther, van C.H.J.; Badenes, G.; Deferm, L.

    2002-01-01

    The improved RF performance of silicon-based technologies over the years and their potential use in telecommunication applications has increased the research in RF modelling of MOS transistors. Especially for analog circuits, accurate RF small signal and large signal transistor models are required.

  4. Complex active regions as the main source of extreme and large solar proton events

    Science.gov (United States)

    Ishkov, V. N.

    2013-12-01

    A study of solar proton sources indicated that solar flare events responsible for ≥2000 pfu proton fluxes mostly occur in complex active regions (CARs), i.e., in transition structures between active regions and activity complexes. Different classes of similar structures and their relation to solar proton events (SPEs) and evolution, depending on the origination conditions, are considered. Arguments in favor of the fact that sunspot groups with extreme dimensions are CARs are presented. An analysis of the flare activity in a CAR resulted in the detection of "physical" boundaries, which separate magnetic structures of the same polarity and are responsible for the independent development of each structure.

  5. The front-end analog and digital signal processing electronics for the drift chambers of the Stanford Large Detector

    International Nuclear Information System (INIS)

    Haller, G.M.; Freytag, D.R.; Fox, J.; Olsen, J.; Paffrath, L.; Yim, A.; Honma, A.

    1990-10-01

    The front-end signal processing electronics for the drift-chambers of the Stanford Large Detector (SLD) at the Stanford Linear Collider is described. The system is implemented with printed-circuit boards which are shaped for direct mounting on the detector. Typically, a motherboard comprises 64 channels of transimpedance amplification and analog waveform sampling, A/D conversion, and associated control and readout circuitry. The loaded motherboard thus forms a processor which records low-level wave forms from 64 detector channels and transforms the information into a 64 k-byte serial data stream. In addition, the package performs calibration functions, measures leakage currents on the wires, and generates wire hit patterns for triggering purposes. The construction and operation of the electronic circuits utilizing monolithic, hybridized, and programmable components are discussed

  6. Retention of habitat complexity minimizes disassembly of reef fish communities following disturbance: a large-scale natural experiment.

    Directory of Open Access Journals (Sweden)

    Michael J Emslie

    Full Text Available High biodiversity ecosystems are commonly associated with complex habitats. Coral reefs are highly diverse ecosystems, but are under increasing pressure from numerous stressors, many of which reduce live coral cover and habitat complexity with concomitant effects on other organisms such as reef fishes. While previous studies have highlighted the importance of habitat complexity in structuring reef fish communities, they employed gradient or meta-analyses which lacked a controlled experimental design over broad spatial scales to explicitly separate the influence of live coral cover from overall habitat complexity. Here a natural experiment using a long term (20 year, spatially extensive (∼ 115,000 kms(2 dataset from the Great Barrier Reef revealed the fundamental importance of overall habitat complexity for reef fishes. Reductions of both live coral cover and habitat complexity had substantial impacts on fish communities compared to relatively minor impacts after major reductions in coral cover but not habitat complexity. Where habitat complexity was substantially reduced, species abundances broadly declined and a far greater number of fish species were locally extirpated, including economically important fishes. This resulted in decreased species richness and a loss of diversity within functional groups. Our results suggest that the retention of habitat complexity following disturbances can ameliorate the impacts of coral declines on reef fishes, so preserving their capacity to perform important functional roles essential to reef resilience. These results add to a growing body of evidence about the importance of habitat complexity for reef fishes, and represent the first large-scale examination of this question on the Great Barrier Reef.

  7. 76 FR 21256 - Proposed Assessment Rate Adjustment Guidelines for Large and Highly Complex Institutions

    Science.gov (United States)

    2011-04-15

    ... and comment are not required and need not be employed to make future changes to the guidelines. [[Page..., including the materiality of guarantees and franchise value. Commenters on the proposed large bank pricing...

  8. Low-complexity R-peak detection in ECG signals: a preliminary step towards ambulatory fetal monitoring.

    Science.gov (United States)

    Rooijakkers, Michiel; Rabotti, Chiara; Bennebroek, Martijn; van Meerbergen, Jef; Mischi, Massimo

    2011-01-01

    Non-invasive fetal health monitoring during pregnancy has become increasingly important. Recent advances in signal processing technology have enabled fetal monitoring during pregnancy, using abdominal ECG recordings. Ubiquitous ambulatory monitoring for continuous fetal health measurement is however still unfeasible due to the computational complexity of noise robust solutions. In this paper an ECG R-peak detection algorithm for ambulatory R-peak detection is proposed, as part of a fetal ECG detection algorithm. The proposed algorithm is optimized to reduce computational complexity, while increasing the R-peak detection quality compared to existing R-peak detection schemes. Validation of the algorithm is performed on two manually annotated datasets, the MIT/BIH Arrhythmia database and an in-house abdominal database. Both R-peak detection quality and computational complexity are compared to state-of-the-art algorithms as described in the literature. With a detection error rate of 0.22% and 0.12% on the MIT/BIH Arrhythmia and in-house databases, respectively, the quality of the proposed algorithm is comparable to the best state-of-the-art algorithms, at a reduced computational complexity.

  9. A potential neural substrate for processing functional classes of complex acoustic signals.

    Directory of Open Access Journals (Sweden)

    Isabelle George

    Full Text Available Categorization is essential to all cognitive processes, but identifying the neural substrates underlying categorization processes is a real challenge. Among animals that have been shown to be able of categorization, songbirds are particularly interesting because they provide researchers with clear examples of categories of acoustic signals allowing different levels of recognition, and they possess a system of specialized brain structures found only in birds that learn to sing: the song system. Moreover, an avian brain nucleus that is analogous to the mammalian secondary auditory cortex (the caudo-medial nidopallium, or NCM has recently emerged as a plausible site for sensory representation of birdsong, and appears as a well positioned brain region for categorization of songs. Hence, we tested responses in this non-primary, associative area to clear and distinct classes of songs with different functions and social values, and for a possible correspondence between these responses and the functional aspects of songs, in a highly social songbird species: the European starling. Our results clearly show differential neuronal responses to the ethologically defined classes of songs, both in the number of neurons responding, and in the response magnitude of these neurons. Most importantly, these differential responses corresponded to the functional classes of songs, with increasing activation from non-specific to species-specific and from species-specific to individual-specific sounds. These data therefore suggest a potential neural substrate for sorting natural communication signals into categories, and for individual vocal recognition of same-species members. Given the many parallels that exist between birdsong and speech, these results may contribute to a better understanding of the neural bases of speech.

  10. Design of complete software GPS signal simulator with low complexity and precise multipath channel model

    Directory of Open Access Journals (Sweden)

    G. Arul Elango

    2016-09-01

    Full Text Available The need for GPS data simulators have become important due to the tremendous growth in the design of versatile GPS receivers. Commercial hardware and software based GPS simulators are expensive and time consuming. In this work, a low cost simple novel GPS L1 signal simulator is designed for testing and evaluating the performance of software GPS receiver in a laboratory environment. A typical real time paradigm, similar to actual satellite derived GPS signal is created on a computer generated scenario. In this paper, a GPS software simulator is proposed that may offer a lot of analysis and testing flexibility to the researchers and developers as it is totally software based primarily running on a laptop/personal computer without the requirement of any hardware. The proposed GPS simulator allows provision for re-configurability and test repeatability and is developed in VC++ platform to minimize the simulation time. It also incorporates Rayleigh multipath channel fading model under non-line of sight (NLOS conditions. In this work, to efficiently design the simulator, several Rayleigh fading models viz. Inverse Discrete Fourier Transform (IDFT, Filtering White Gaussian Noise (FWFN and modified Sum of Sinusoidal (SOS simulators are tested and compared in terms of accuracy of its first and second order statistical metrics, execution time and the later one is found to be as the best appropriate Rayleigh multipath model suitable for incorporating with GPS simulator. The fading model written in ‘MATLAB’ engine has been linked with software GPS simulator module enable to test GPS receiver’s functionality in different fading environments.

  11. IL-7 Induces an Epitope Masking of γc Protein in IL-7 Receptor Signaling Complex

    Directory of Open Access Journals (Sweden)

    Tae Sik Goh

    2017-01-01

    Full Text Available IL-7 signaling via IL-7Rα and common γ-chain (γc is necessary for the development and homeostasis of T cells. Although the delicate mechanism in which IL-7Rα downregulation allows the homeostasis of T cell with limited IL-7 has been well known, the exact mechanism behind the interaction between IL-7Rα and γc in the absence or presence of IL-7 remains unclear. Additionally, we are still uncertain as to how only IL-7Rα is separately downregulated by the binding of IL-7 from the IL-7Rα/γc complex. We demonstrate here that 4G3, TUGm2, and 3E12 epitope masking of γc protein are induced in the presence of IL-7, indicating that the epitope alteration is induced by IL-7 binding to the preassembled receptor core. Moreover, the epitope masking of γc protein is inversely correlated with the expression of IL-7Rα upon IL-7 binding, implying that the structural alteration of γc might be involved in the regulation of IL-7Rα expression. The conformational change in γc upon IL-7 binding may contribute not only to forming the functional IL-7 signaling complex but also to optimally regulating the expression of IL-7Rα.

  12. IL-7 Induces an Epitope Masking of γc Protein in IL-7 Receptor Signaling Complex

    Science.gov (United States)

    Goh, Tae Sik; Jo, Yuna; Lee, Byunghyuk; Kim, Geona; Hwang, Hyunju; Ko, Eunhee; Kang, Seung Wan; Oh, Sae-Ock; Baek, Sun-Yong; Yoon, Sik; Lee, Jung Sub

    2017-01-01

    IL-7 signaling via IL-7Rα and common γ-chain (γc) is necessary for the development and homeostasis of T cells. Although the delicate mechanism in which IL-7Rα downregulation allows the homeostasis of T cell with limited IL-7 has been well known, the exact mechanism behind the interaction between IL-7Rα and γc in the absence or presence of IL-7 remains unclear. Additionally, we are still uncertain as to how only IL-7Rα is separately downregulated by the binding of IL-7 from the IL-7Rα/γc complex. We demonstrate here that 4G3, TUGm2, and 3E12 epitope masking of γc protein are induced in the presence of IL-7, indicating that the epitope alteration is induced by IL-7 binding to the preassembled receptor core. Moreover, the epitope masking of γc protein is inversely correlated with the expression of IL-7Rα upon IL-7 binding, implying that the structural alteration of γc might be involved in the regulation of IL-7Rα expression. The conformational change in γc upon IL-7 binding may contribute not only to forming the functional IL-7 signaling complex but also to optimally regulating the expression of IL-7Rα. PMID:28127156

  13. A comparative analysis of Indoor WiFi Positioning at a large building complex

    DEFF Research Database (Denmark)

    Mathisen, Andreas; Krogh, Søren; Stisen, Allan

    2016-01-01

    Indoor Positioning based on WiFi has received extensive focus from research communities, owing its promises of ubiquitous positioning indoors for a variety of applications. The majority of the existing research on WiFi positioning centers around the improvement of positioning accuracy. However...... are in daily use. The positioning methods covered utilizes received signal strength from existing WiFi infrastructure to ease deployment and maintenance. We identify meaningful key metrics which describe different aspects of the methods’ performance. Using these metrics, we furthermore report on experiences...

  14. A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling

    Science.gov (United States)

    Beautrait, Alexandre; Paradis, Justine S.; Zimmerman, Brandon; Giubilaro, Jenna; Nikolajev, Ljiljana; Armando, Sylvain; Kobayashi, Hiroyuki; Yamani, Lama; Namkung, Yoon; Heydenreich, Franziska M.; Khoury, Etienne; Audet, Martin; Roux, Philippe P.; Veprintsev, Dmitry B.; Laporte, Stéphane A.; Bouvier, Michel

    2017-04-01

    In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes. This selective β-arrestin/β2-adaptin inhibitor (Barbadin) blocks agonist-promoted endocytosis of the prototypical β2-adrenergic (β2AR), V2-vasopressin (V2R) and angiotensin-II type-1 (AT1R) receptors, but does not affect β-arrestin-independent (transferrin) or AP2-independent (endothelin-A) receptor internalization. Interestingly, Barbadin fully blocks V2R-stimulated ERK1/2 activation and blunts cAMP accumulation promoted by both V2R and β2AR, supporting the concept of β-arrestin/AP2-dependent signalling for both G protein-dependent and -independent pathways.

  15. Hypothalamic roles of mTOR complex I: integration of nutrient and hormone signals to regulate energy homeostasis.

    Science.gov (United States)

    Hu, Fang; Xu, Yong; Liu, Feng

    2016-06-01

    Mammalian or mechanistic target of rapamycin (mTOR) senses nutrient, energy, and hormone signals to regulate metabolism and energy homeostasis. mTOR activity in the hypothalamus, which is associated with changes in energy status, plays a critical role in the regulation of food intake and body weight. mTOR integrates signals from a variety of "energy balancing" hormones such as leptin, insulin, and ghrelin, although its action varies in response to these distinct hormonal stimuli as well as across different neuronal populations. In this review, we summarize and highlight recent findings regarding the functional roles of mTOR complex 1 (mTORC1) in the hypothalamus specifically in its regulation of body weight, energy expenditure, and glucose/lipid homeostasis. Understanding the role and underlying mechanisms behind mTOR-related signaling in the brain will undoubtedly pave new avenues for future therapeutics and interventions that can combat obesity, insulin resistance, and diabetes. Copyright © 2016 the American Physiological Society.

  16. Rapid, topology-based particle tracking for high-resolution measurements of large complex 3D motion fields.

    Science.gov (United States)

    Patel, Mohak; Leggett, Susan E; Landauer, Alexander K; Wong, Ian Y; Franck, Christian

    2018-04-03

    Spatiotemporal tracking of tracer particles or objects of interest can reveal localized behaviors in biological and physical systems. However, existing tracking algorithms are most effective for relatively low numbers of particles that undergo displacements smaller than their typical interparticle separation distance. Here, we demonstrate a single particle tracking algorithm to reconstruct large complex motion fields with large particle numbers, orders of magnitude larger than previously tractably resolvable, thus opening the door for attaining very high Nyquist spatial frequency motion recovery in the images. Our key innovations are feature vectors that encode nearest neighbor positions, a rigorous outlier removal scheme, and an iterative deformation warping scheme. We test this technique for its accuracy and computational efficacy using synthetically and experimentally generated 3D particle images, including non-affine deformation fields in soft materials, complex fluid flows, and cell-generated deformations. We augment this algorithm with additional particle information (e.g., color, size, or shape) to further enhance tracking accuracy for high gradient and large displacement fields. These applications demonstrate that this versatile technique can rapidly track unprecedented numbers of particles to resolve large and complex motion fields in 2D and 3D images, particularly when spatial correlations exist.

  17. Large, dynamic, multi-protein complexes: a challenge for structural biology

    Czech Academy of Sciences Publication Activity Database

    Rozycki, B.; Bouřa, Evžen

    2014-01-01

    Roč. 26, č. 46 (2014), 463103/1-463103/11 ISSN 0953-8984 R&D Projects: GA MŠk LO1302 EU Projects: European Commission(XE) 333916 - STARPI4K Institutional support: RVO:61388963 Keywords : protein structure * multi-protein complexes * hybrid methods of structural biology Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.346, year: 2014

  18. Building flexibility and managing complexity in community mental health: lessons learned in a large urban centre.

    Science.gov (United States)

    Stergiopoulos, Vicky; Saab, Dima; Francombe Pridham, Kate; Aery, Anjana; Nakhost, Arash

    2018-01-24

    Across many jurisdictions, adults with complex mental health and social needs face challenges accessing appropriate supports due to system fragmentation and strict eligibility criteria of existing services. To support this underserviced population, Toronto's local health authority launched two novel community mental health models in 2014, inspired by Flexible Assertive Community Team principles. This study explores service user and provider perspectives on the acceptability of these services, and lessons learned during early implementation. We purposively sampled 49 stakeholders (staff, physicians, service users, health systems stakeholders) and conducted 17 semi-structured qualitative interviews and 5 focus groups between October 23, 2014 and March 2, 2015, exploring stakeholder perspectives on the newly launched team based models, as well as activities and strategies employed to support early implementation. Interviews and focus groups were audio recorded, transcribed verbatim and analyzed using thematic analysis. Findings revealed wide-ranging endorsement for the two team-based models' success in engaging the target population of adults with complex service needs. Implementation strengths included the broad recognition of existing service gaps, the use of interdisciplinary teams and experienced service providers, broad partnerships and collaboration among various service sectors, training and team building activities. Emerging challenges included lack of complementary support services such as suitable housing, organizational contexts reluctant to embrace change and risk associated with complexity, as well as limited service provider and organizational capacity to deliver evidence-based interventions. Findings identified implementation drivers at the practitioner, program, and system levels, specific to the implementation of community mental health interventions for adults with complex health and social needs. These can inform future efforts to address the health

  19. Large Eddy Simulations of Complex Flows in IC-Engine's Exhaust Manifold and Turbine

    OpenAIRE

    Fjällman, Johan

    2014-01-01

    The thesis deals with the flow in pipe bends and radial turbines geometries that are commonly found in an Internal Combustion Engine (ICE). The development phase of internal combustion engines relies more and more on simulations as an important complement to experiments. This is partly because of the reduction in development cost and the shortening of the development time. This is one of the reasons for the need of more accurate and predictive simulations. By using more complex computational ...

  20. Scaling and application of commercial, feature-rich, modular mixed-signal technology platforms for large format ROICs

    Science.gov (United States)

    Kar-Roy, Arjun; Racanelli, Marco; Howard, David; Miyagi, Glenn; Bowler, Mark; Jordan, Scott; Zhang, Tao; Krieger, William

    2010-04-01

    Today's modular, mixed-signal CMOS process platforms are excellent choices for manufacturing of highly integrated, large-format read out integrated circuits (ROICs). Platform features, that can be used for both cooled and un-cooled ROIC applications, can include (1) quality passives such as 4fFμm2 stacked MIM capacitors for linearity and higher density capacitance per pixel, 1kOhm high-value poly-silicon resistors, 2.8μm thick metals for efficient power distribution and reduced I-R drop; (2) analog active devices such as low noise single gate 3.3V, and 1.8V/3.3V or 1.8V/5V dual gate configurations, 40V LDMOS FETs, and NPN and PNP devices, deep n-well for substrate isolation for analog blocks and digital logic; (3) tools to assist the circuit designer such as models for cryogenic temperatures, CAD assistance for metal density uniformity determination, statistical, X-sigma and PCM-based models for corner validation and to simulate design sensitivity, and (4) sub-field stitching for large die. The TowerJazz platform of technology for 0.50μm, 0.25μm and 0.18μm CMOS nodes, with features as described above, is described in detail in this paper.

  1. Differences in passenger car and large truck involved crash frequencies at urban signalized intersections: an exploratory analysis.

    Science.gov (United States)

    Dong, Chunjiao; Clarke, David B; Richards, Stephen H; Huang, Baoshan

    2014-01-01

    The influence of intersection features on safety has been examined extensively because intersections experience a relatively large proportion of motor vehicle conflicts and crashes. Although there are distinct differences between passenger cars and large trucks-size, operating characteristics, dimensions, and weight-modeling crash counts across vehicle types is rarely addressed. This paper develops and presents a multivariate regression model of crash frequencies by collision vehicle type using crash data for urban signalized intersections in Tennessee. In addition, the performance of univariate Poisson-lognormal (UVPLN), multivariate Poisson (MVP), and multivariate Poisson-lognormal (MVPLN) regression models in establishing the relationship between crashes, traffic factors, and geometric design of roadway intersections is investigated. Bayesian methods are used to estimate the unknown parameters of these models. The evaluation results suggest that the MVPLN model possesses most of the desirable statistical properties in developing the relationships. Compared to the UVPLN and MVP models, the MVPLN model better identifies significant factors and predicts crash frequencies. The findings suggest that traffic volume, truck percentage, lighting condition, and intersection angle significantly affect intersection safety. Important differences in car, car-truck, and truck crash frequencies with respect to various risk factors were found to exist between models. The paper provides some new or more comprehensive observations that have not been covered in previous studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Signal formation processes in Micromegas detectors and quality control for large size detector construction for the ATLAS new small wheel

    Energy Technology Data Exchange (ETDEWEB)

    Kuger, Fabian

    2017-07-31

    The Micromegas technology is one of the most successful modern gaseous detector concepts and widely utilized in nuclear and particle physics experiments. Twenty years of R and D rendered the technology sufficiently mature to be selected as precision tracking detector for the New Small Wheel (NSW) upgrade of the ATLAS Muon spectrometer. This will be the first large scale application of Micromegas in one of the major LHC experiments. However, many of the fundamental microscopic processes in these gaseous detectors are still not fully understood and studies on several detector aspects, like the micromesh geometry, have never been addressed systematically. The studies on signal formation in Micromegas, presented in the first part of this thesis, focuses on the microscopic signal electron loss mechanisms and the amplification processes in electron gas interaction. Based on a detailed model of detector parameter dependencies, these processes are scrutinized in an iterating comparison between experimental results, theory prediction of the macroscopic observables and process simulation on the microscopic level. Utilizing the specialized detectors developed in the scope of this thesis as well as refined simulation algorithms, an unprecedented level of accuracy in the description of the microscopic processes is reached, deepening the understanding of the fundamental process in gaseous detectors. The second part is dedicated to the challenges arising with the large scale Micromegas production for the ATLAS NSW. A selection of technological choices, partially influenced or determined by the herein presented studies, are discussed alongside a final report on two production related tasks addressing the detectors' core components: For the industrial production of resistive anode PCBs a detailed quality control (QC) and quality assurance (QA) scheme as well as the therefore required testing tools have been developed. In parallel the study on micromesh parameter optimization

  3. Signal formation processes in Micromegas detectors and quality control for large size detector construction for the ATLAS new small wheel

    International Nuclear Information System (INIS)

    Kuger, Fabian

    2017-01-01

    The Micromegas technology is one of the most successful modern gaseous detector concepts and widely utilized in nuclear and particle physics experiments. Twenty years of R and D rendered the technology sufficiently mature to be selected as precision tracking detector for the New Small Wheel (NSW) upgrade of the ATLAS Muon spectrometer. This will be the first large scale application of Micromegas in one of the major LHC experiments. However, many of the fundamental microscopic processes in these gaseous detectors are still not fully understood and studies on several detector aspects, like the micromesh geometry, have never been addressed systematically. The studies on signal formation in Micromegas, presented in the first part of this thesis, focuses on the microscopic signal electron loss mechanisms and the amplification processes in electron gas interaction. Based on a detailed model of detector parameter dependencies, these processes are scrutinized in an iterating comparison between experimental results, theory prediction of the macroscopic observables and process simulation on the microscopic level. Utilizing the specialized detectors developed in the scope of this thesis as well as refined simulation algorithms, an unprecedented level of accuracy in the description of the microscopic processes is reached, deepening the understanding of the fundamental process in gaseous detectors. The second part is dedicated to the challenges arising with the large scale Micromegas production for the ATLAS NSW. A selection of technological choices, partially influenced or determined by the herein presented studies, are discussed alongside a final report on two production related tasks addressing the detectors' core components: For the industrial production of resistive anode PCBs a detailed quality control (QC) and quality assurance (QA) scheme as well as the therefore required testing tools have been developed. In parallel the study on micromesh parameter optimization

  4. Evaluation of phosphopeptide enrichment strategies for quantitative TMT analysis of complex network dynamics in cancer-associated cell signalling

    Directory of Open Access Journals (Sweden)

    Benedetta Lombardi

    2015-03-01

    Full Text Available Defining alterations in signalling pathways in normal and malignant cells is becoming a major field in proteomics. A number of different approaches have been established to isolate, identify and quantify phosphorylated proteins and peptides. In the current report, a comparison between SCX prefractionation versus an antibody based approach, both coupled to TiO2 enrichment and applied to TMT labelled cellular lysates, is described. The antibody strategy was more complete for enriching phosphopeptides and allowed the identification of a large set of proteins known to be phosphorylated (715 protein groups with a minimum number of not previously known phosphorylated proteins (2.

  5. Automated NMR fragment based screening identified a novel interface blocker to the LARG/RhoA complex.

    Directory of Open Access Journals (Sweden)

    Jia Gao

    Full Text Available The small GTPase cycles between the inactive GDP form and the activated GTP form, catalyzed by the upstream guanine exchange factors. The modulation of such process by small molecules has been proven to be a fruitful route for therapeutic intervention to prevent the over-activation of the small GTPase. The fragment based approach emerging in the past decade has demonstrated its paramount potential in the discovery of inhibitors targeting such novel and challenging protein-protein interactions. The details regarding the procedure of NMR fragment screening from scratch have been rarely disclosed comprehensively, thus restricts its wider applications. To achieve a consistent screening applicable to a number of targets, we developed a highly automated protocol to cover every aspect of NMR fragment screening as possible, including the construction of small but diverse libray, determination of the aqueous solubility by NMR, grouping compounds with mutual dispersity to a cocktail, and the automated processing and visualization of the ligand based screening spectra. We exemplified our streamlined screening in RhoA alone and the complex of the small GTPase RhoA and its upstream guanine exchange factor LARG. Two hits were confirmed from the primary screening in cocktail and secondary screening over individual hits for LARG/RhoA complex, while one of them was also identified from the screening for RhoA alone. HSQC titration of the two hits over RhoA and LARG alone, respectively, identified one compound binding to RhoA.GDP at a 0.11 mM affinity, and perturbed the residues at the switch II region of RhoA. This hit blocked the formation of the LARG/RhoA complex, validated by the native gel electrophoresis, and the titration of RhoA to ¹⁵N labeled LARG in the absence and presence the compound, respectively. It therefore provides us a starting point toward a more potent inhibitor to RhoA activation catalyzed by LARG.

  6. Electromagnetic modelling of large complex 3-D structures with LEGO and the eigencurrent expansion method

    NARCIS (Netherlands)

    Lancellotti, V.; Hon, de B.P.; Tijhuis, A.G.

    2009-01-01

    Linear embedding via Green's operators (LEGO) is a computational method in which the multiple scattering between adjacent objects - forming a large composite structure - is determined through the interaction of simple-shaped building domains, whose electromagnetic (EM) behavior is accounted for by

  7. From Collective Knowledge to Intelligence : Pre-Requirements Analysis of Large and Complex Systems

    NARCIS (Netherlands)

    Liang, Peng; Avgeriou, Paris; He, Keqing; Xu, Lai

    2010-01-01

    Requirements engineering is essentially a social collaborative activity in which involved stakeholders have to closely work together to communicate, elicit, negotiate, define, confirm, and finally come up with the requirements for the system to be implemented or upgraded. In the development of large

  8. A constraint logic programming approach to associate 1D and 3D structural components for large protein complexes.

    Science.gov (United States)

    Dal Palù, Alessandro; Pontelli, Enrico; He, Jing; Lu, Yonggang

    2007-01-01

    The paper describes a novel framework, constructed using Constraint Logic Programming (CLP) and parallelism, to determine the association between parts of the primary sequence of a protein and alpha-helices extracted from 3D low-resolution descriptions of large protein complexes. The association is determined by extracting constraints from the 3D information, regarding length, relative position and connectivity of helices, and solving these constraints with the guidance of a secondary structure prediction algorithm. Parallelism is employed to enhance performance on large proteins. The framework provides a fast, inexpensive alternative to determine the exact tertiary structure of unknown proteins.

  9. Large Differences in the Optical Spectrum Associated with the Same Complex: The Effect of the Anisotropy of the Embedding Lattice

    DEFF Research Database (Denmark)

    Aramburu, José Antonio; García-Fernández, Pablo; García Lastra, Juan Maria

    2017-01-01

    of the electric field created by the rest of lattice ions over the complex. To illustrate this concept we analyze the origin of the surprisingly large differences in the d–d optical transitions of two systems containing square-planar CuF42– complexes, CaCuF4, and center II in Cu2+-doped Ba2ZnF6, even though...... the Cu2+–F–distance difference is just found to be 1%. Using a minimalist first-principles model we show that the different morphology of the host lattices creates an anisotropic field that red-shifts the in vacuo complex transitions to the 1.25–1.70 eV range in CaCuF4, while it blue-shifts them to the 1...

  10. Direct Observation of Very Large Zero-Field Splitting in a Tetrahedral Ni(II)Se4 Coordination Complex.

    Science.gov (United States)

    Jiang, Shang-Da; Maganas, Dimitrios; Levesanos, Nikolaos; Ferentinos, Eleftherios; Haas, Sabrina; Thirunavukkuarasu, Komalavalli; Krzystek, J; Dressel, Martin; Bogani, Lapo; Neese, Frank; Kyritsis, Panayotis

    2015-10-14

    The high-spin (S = 1) tetrahedral Ni(II) complex [Ni{(i)Pr2P(Se)NP(Se)(i)Pr2}2] was investigated by magnetometry, spectroscopic, and quantum chemical methods. Angle-resolved magnetometry studies revealed the orientation of the magnetization principal axes. The very large zero-field splitting (zfs), D = 45.40(2) cm(-1), E = 1.91(2) cm(-1), of the complex was accurately determined by far-infrared magnetic spectroscopy, directly observing transitions between the spin sublevels of the triplet ground state. These are the largest zfs values ever determined--directly--for a high-spin Ni(II) complex. Ab initio calculations further probed the electronic structure of the system, elucidating the factors controlling the sign and magnitude of D. The latter is dominated by spin-orbit coupling contributions of the Ni ions, whereas the corresponding effects of the Se atoms are remarkably smaller.

  11. Metal Dependence of Signal Transmission through MolecularQuantum-Dot Cellular Automata (QCA: A Theoretical Studyon Fe, Ru, and Os Mixed-Valence Complexes

    Directory of Open Access Journals (Sweden)

    Ken Tokunaga

    2010-08-01

    Full Text Available Dynamic behavior of signal transmission through metal complexes [L5M-BL-ML5]5+ (M=Fe, Ru, Os, BL=pyrazine (py, 4,4’-bipyridine (bpy, L=NH3, which are simplified models of the molecular quantum-dot cellular automata (molecular QCA, is discussed from the viewpoint of one-electron theory, density functional theory. It is found that for py complexes, the signal transmission time (tst is Fe(0.6 fs < Os(0.7 fs < Ru(1.1 fs and the signal amplitude (A is Fe(0.05 e < Os(0.06 e < Ru(0.10 e. For bpy complexes, tst and A are Fe(1.4 fs < Os(1.7 fs < Ru(2.5 fs and Os(0.11 e < Ru(0.12 e complexes generally have stronger signal amplitude, but waste longer time for signal transmission than py complexes. Among all complexes, Fe complex with bpy BL shows the best result. These results are discussed from overlap integral and energy gap of molecular orbitals.

  12. TOR complex 2-Ypk1 signaling is an essential positive regulator of the general amino acid control response and autophagy.

    Science.gov (United States)

    Vlahakis, Ariadne; Graef, Martin; Nunnari, Jodi; Powers, Ted

    2014-07-22

    The highly conserved Target of Rapamycin (TOR) kinase is a central regulator of cell growth and metabolism in response to nutrient availability. TOR functions in two structurally and functionally distinct complexes, TOR Complex 1 (TORC1) and TOR Complex 2 (TORC2). Through TORC1, TOR negatively regulates autophagy, a conserved process that functions in quality control and cellular homeostasis and, in this capacity, is part of an adaptive nutrient deprivation response. Here we demonstrate that during amino acid starvation TOR also operates independently as a positive regulator of autophagy through the conserved TORC2 and its downstream target protein kinase, Ypk1. Under these conditions, TORC2-Ypk1 signaling negatively regulates the Ca(2+)/calmodulin-dependent phosphatase, calcineurin, to enable the activation of the amino acid-sensing eIF2α kinase, Gcn2, and to promote autophagy. Our work reveals that the TORC2 pathway regulates autophagy in an opposing manner to TORC1 to provide a tunable response to cellular metabolic status.

  13. Close relationship between fMRI signals and transient heart rate changes accompanying K-complex. Simultaneous EEG/fMRI study

    International Nuclear Information System (INIS)

    Kan, Shigeyuki; Koike, Takahiko; Miyauchi, Satoru; Misaki, Masaya

    2009-01-01

    Combining functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) allows the investigation of spontaneous activities in the human brain. Recently, by using this technique, increases in fMRI signal accompanying transient EEG activities such as sleep spindles and slow waves were reported. Although these fMRI signal increases appear to arise as a result of the neural activities being reflected in the EEG, when the influence of physiological activities upon fMRI signals are taken into consideration, it is highly controversial that fMRI signal increases accompanying transient EEG activities reflect actual neural activities. In the present study, we conducted simultaneous fMRI and polysomnograph recording of 18 normal adults, to study the effect of transient heart rate changes after a K-complex on fMRI signals. Significant fMRI signal increase was observed in the cerebellum, the ventral thalamus, the dorsal part of the brainstem, the periventricular white matter and the ventricle (quadrigeminal cistern). On the other hand, significant fMRI signal decrease was observed only in the right insula. Moreover, intensities of fMRI signal increase that was accompanied by a K-complex correlated positively with the magnitude of heart rate changes after a K-complex. Previous studies have reported that K-complex is closely related with sympathetic nervous activity and that the attributes of perfusion regulation in the brain differ during wakefulness and sleep. By taking these findings into consideration, our present results indicate that a close relationship exists between a K-complex and the changes in cardio- and neurovascular regulations that are mediated by the autonomic nervous system during sleep; further, these results indicate that transient heart rate changes after a K-complex can affect the fMRI signal generated in certain brain regions. (author)

  14. Three-dimensional coupled Monte Carlo-discrete ordinates computational scheme for shielding calculations of large and complex nuclear facilities

    International Nuclear Information System (INIS)

    Chen, Y.; Fischer, U.

    2005-01-01

    Shielding calculations of advanced nuclear facilities such as accelerator based neutron sources or fusion devices of the tokamak type are complicated due to their complex geometries and their large dimensions, including bulk shields of several meters thickness. While the complexity of the geometry in the shielding calculation can be hardly handled by the discrete ordinates method, the deep penetration of radiation through bulk shields is a severe challenge for the Monte Carlo particle transport technique. This work proposes a dedicated computational scheme for coupled Monte Carlo-Discrete Ordinates transport calculations to handle this kind of shielding problems. The Monte Carlo technique is used to simulate the particle generation and transport in the target region with both complex geometry and reaction physics, and the discrete ordinates method is used to treat the deep penetration problem in the bulk shield. The coupling scheme has been implemented in a program system by loosely integrating the Monte Carlo transport code MCNP, the three-dimensional discrete ordinates code TORT and a newly developed coupling interface program for mapping process. Test calculations were performed with comparison to MCNP solutions. Satisfactory agreements were obtained between these two approaches. The program system has been chosen to treat the complicated shielding problem of the accelerator-based IFMIF neutron source. The successful application demonstrates that coupling scheme with the program system is a useful computational tool for the shielding analysis of complex and large nuclear facilities. (authors)

  15. Methods for the preparation of large quantities of complex single-stranded oligonucleotide libraries.

    Science.gov (United States)

    Murgha, Yusuf E; Rouillard, Jean-Marie; Gulari, Erdogan

    2014-01-01

    Custom-defined oligonucleotide collections have a broad range of applications in fields of synthetic biology, targeted sequencing, and cytogenetics. Also, they are used to encode information for technologies like RNA interference, protein engineering and DNA-encoded libraries. High-throughput parallel DNA synthesis technologies developed for the manufacture of DNA microarrays can produce libraries of large numbers of different oligonucleotides, but in very limited amounts. Here, we compare three approaches to prepare large quantities of single-stranded oligonucleotide libraries derived from microarray synthesized collections. The first approach, alkaline melting of double-stranded PCR amplified libraries with a biotinylated strand captured on streptavidin coated magnetic beads results in little or no non-biotinylated ssDNA. The second method wherein the phosphorylated strand of PCR amplified libraries is nucleolyticaly hydrolyzed is recommended when small amounts of libraries are needed. The third method combining in vitro transcription of PCR amplified libraries to reverse transcription of the RNA product into single-stranded cDNA is our recommended method to produce large amounts of oligonucleotide libraries. Finally, we propose a method to remove any primer binding sequences introduced during library amplification.

  16. Intermolecular symmetry-adapted perturbation theory study of large organic complexes

    International Nuclear Information System (INIS)

    Heßelmann, Andreas; Korona, Tatiana

    2014-01-01

    Binding energies for the complexes of the S12L database by Grimme [Chem. Eur. J. 18, 9955 (2012)] were calculated using intermolecular symmetry-adapted perturbation theory combined with a density-functional theory description of the interacting molecules. The individual interaction energy decompositions revealed no particular change in the stabilisation pattern as compared to smaller dimer systems at equilibrium structures. This demonstrates that, to some extent, the qualitative description of the interaction of small dimer systems may be extrapolated to larger systems, a method that is widely used in force-fields in which the total interaction energy is decomposed into atom-atom contributions. A comparison of the binding energies with accurate experimental reference values from Grimme, the latter including thermodynamic corrections from semiempirical calculations, has shown a fairly good agreement to within the error range of the reference binding energies

  17. Development of large scale industrial complex and its pollution. Case study of Kashima area

    Energy Technology Data Exchange (ETDEWEB)

    Nagai, S

    1975-01-01

    The development of Kashima industrial complex which embraces three townships started in 1960 to promote both agricultural and industrial developments using the most advanced techniques available for environmental pollution control. The chronological development progress is described with reference to the capital investment, gross product, employment and labor supply, population, status of the use of agricultural land, annual revenue and expenditure of three townships, and township tax. The environmental pollution control policies and measures taken since 1964 are reviewed. The emphasis was placed on preliminary investigations by various means and emission standards were applied. However, many incidences of pollution damage occurred due to operational errors and accidental causes. The emission quantity of sulfur dioxide is to be reduced from 8212 N cu m/h in 1973 to 4625 N cu m/h in 1976.

  18. Magnetic storm generation by large-scale complex structure Sheath/ICME

    Science.gov (United States)

    Grigorenko, E. E.; Yermolaev, Y. I.; Lodkina, I. G.; Yermolaev, M. Y.; Riazantseva, M.; Borodkova, N. L.

    2017-12-01

    We study temporal profiles of interplanetary plasma and magnetic field parameters as well as magnetospheric indices. We use our catalog of large-scale solar wind phenomena for 1976-2000 interval (see the catalog for 1976-2016 in web-side ftp://ftp.iki.rssi.ru/pub/omni/ prepared on basis of OMNI database (Yermolaev et al., 2009)) and the double superposed epoch analysis method (Yermolaev et al., 2010). Our analysis showed (Yermolaev et al., 2015) that average profiles of Dst and Dst* indices decrease in Sheath interval (magnetic storm activity increases) and increase in ICME interval. This profile coincides with inverted distribution of storm numbers in both intervals (Yermolaev et al., 2017). This behavior is explained by following reasons. (1) IMF magnitude in Sheath is higher than in Ejecta and closed to value in MC. (2) Sheath has 1.5 higher efficiency of storm generation than ICME (Nikolaeva et al., 2015). The most part of so-called CME-induced storms are really Sheath-induced storms and this fact should be taken into account during Space Weather prediction. The work was in part supported by the Russian Science Foundation, grant 16-12-10062. References. 1. Nikolaeva N.S., Y. I. Yermolaev and I. G. Lodkina (2015), Modeling of the corrected Dst* index temporal profile on the main phase of the magnetic storms generated by different types of solar wind, Cosmic Res., 53(2), 119-127 2. Yermolaev Yu. I., N. S. Nikolaeva, I. G. Lodkina and M. Yu. Yermolaev (2009), Catalog of Large-Scale Solar Wind Phenomena during 1976-2000, Cosmic Res., , 47(2), 81-94 3. Yermolaev, Y. I., N. S. Nikolaeva, I. G. Lodkina, and M. Y. Yermolaev (2010), Specific interplanetary conditions for CIR-induced, Sheath-induced, and ICME-induced geomagnetic storms obtained by double superposed epoch analysis, Ann. Geophys., 28, 2177-2186 4. Yermolaev Yu. I., I. G. Lodkina, N. S. Nikolaeva and M. Yu. Yermolaev (2015), Dynamics of large-scale solar wind streams obtained by the double superposed epoch

  19. Glycemic Control, Hand Activity, and Complexity of Biological Signals in Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Hsien-Tsai Wu

    2017-01-01

    Full Text Available Both glycemic control and handgrip strength affect microvascular function. Multiscale entropy (MSE of photoplethysmographic (PPG pulse amplitudes may differ by diabetes status and hand activity. Of a middle-to-old aged and right-handed cohort without clinical cardiovascular disease, we controlled age, sex, and weight to select the unaffected (no type 2 diabetes, n=36, the well-controlled diabetes (HbA1c < 8%, n=22, and the poorly controlled diabetes (HbA1c ≥ 8%, n=22 groups. MSEs were calculated from consecutive 1,500 PPG pulse amplitudes of bilateral index fingertips. The small-,  medium-, and large-scale MSEs were defined as the average of scale 1 (MSE1, scales 2–4 (MSE2–4, and scales 5–10 (MSE5–10, respectively. Intra- and intergroups were compared by one- and two-sample t-tests, respectively. The dominant hand MSE5–10 was lower in the poorly controlled diabetes group than the well-controlled diabetes and the unaffected (1.28 versus 1.52 and 1.56, p=0.019 and 0.001, resp. groups, whereas the nondominant hand MSE5–10 was lower in the well- and poorly controlled diabetes groups than the unaffected group (1.35 and 1.29 versus 1.58, p=0.008 and 0.005, resp.. The MSE1 of dominant hand was higher than that of nondominant hand in the well-controlled diabetes (1.35 versus 1.10, p=0.048. In conclusion, diabetes status and hand dominance may affect the MSE of PPG pulse amplitudes.

  20. Evaluating greenhouse gas emissions from hydropower complexes on large rivers in Eastern Washington

    Energy Technology Data Exchange (ETDEWEB)

    Arntzen, Evan V.; Miller, Benjamin L.; O' Toole, Amanda C.; Niehus, Sara E.; Richmond, Marshall C.

    2013-03-15

    Water bodies, such as freshwater lakes, are known to be net emitters of carbon dioxide (CO2), and methane (CH4). In recent years, significant greenhouse gas (GHG) emissions from tropical, boreal, and mid-latitude reservoirs have been reported. At a time when hydropower is increasing worldwide, better understanding of seasonal and regional variation in GHG emissions is needed in order to develop a predictive understanding of such fluxes within man-made impoundments. We examined power-producing dam complexes within xeric temperate locations in the northwestern United States. Sampling environments on the Snake (Lower Monumental Dam Complex) and Columbia Rivers (Priest Rapids Dam Complex) included tributary, mainstem, embayment, forebay, and tailrace areas during winter and summer 2012. At each sampling location, GHG measurement pathways included surface gas flux, degassing as water passed through dams during power generation, ebullition within littoral embayments, and direct sampling of hyporheic pore-water. Measurements were also carried out in a free-flowing reach of the Columbia River to estimate unaltered conditions. Surface flux resulted in very low emissions, with reservoirs acting as a sink for CO2 (up to –262 mg m-2 d-1, which is within the range previously reported for similarly located reservoirs). Surface flux of methane remained below 1 mg CH4 m-2d-1, a value well below fluxes reported previously for temperate reservoirs. Water passing through hydroelectric projects acted as a sink for CO2 during winter and a small source during summer, with mean degassing fluxes of –117 and 4.5 t CO2 d-1, respectively. Degassing of CH4 was minimal, with mean fluxes of 3.1 × 10-6 and –5.6 × 10-4 t CH4 d-1 during winter and summer, respectively. Gas flux due to ebullition was greater in coves located within reservoirs than in coves within the free flowing Hanford Reach–and CH4 flux exceeded that of CO2. Methane emissions varied widely across sampling locations

  1. Hsp27 regulates Akt activation and polymorphonuclear leukocyte apoptosis by scaffolding MK2 to Akt signal complex.

    Science.gov (United States)

    Wu, Rui; Kausar, Hina; Johnson, Paul; Montoya-Durango, Diego E; Merchant, Michael; Rane, Madhavi J

    2007-07-27

    We have shown previously that Akt exists in a signal complex with p38 MAPK, MAPK-activated protein kinase-2 (MK2), and heat shock protein 27 (Hsp27) and MK2 phosphorylates Akt on Ser-473. Additionally, dissociation of Hsp27 from Akt, prior to Akt activation, induced polymorphonuclear leukocyte (PMN) apoptosis. However, the role of Hsp27 in regulating Akt activation was not examined. This study tested the hypothesis that Hsp27 regulates Akt activation and promotes cell survival by scaffolding MK2 to the Akt signal complex. Here we show that loss of Akt/Hsp27 interaction by anti-Hsp27 antibody treatment resulted in loss of Akt/MK2 interaction, loss of Akt-Ser-473 phosphorylation, and induced PMN apoptosis. Transfection of myristoylated Akt (AktCA) in HK-11 cells induced Akt-Ser-473 phosphorylation, activation, and Hsp27-Ser-82 phosphorylation. Cotransfection of AktCA with Hsp27 short interfering RNA, but not scrambled short interfering RNA, silenced Hsp27 expression, without altering Akt expression in HK-11 cells. Silencing Hsp27 expression inhibited Akt/MK2 interaction, inhibited Akt phosphorylation and Akt activation, and induced HK-11 cell death. Deletion mutagenesis studies identified acidic linker region (amino acids 117-128) on Akt as an Hsp27 binding region. Deletion of amino acids 117-128 on Akt resulted in loss of its interaction with Hsp27 and MK2 but not with Hsp90 as demonstrated by immunoprecipitation and glutathione S-transferase pulldown studies. Co-transfection studies demonstrated that constitutively active MK2 (MK2EE) phosphorylated Aktwt (wild type) on Ser-473 but failed to phosphorylate Akt(Delta117-128) mutant in transfixed cells. These studies collectively define a novel role of Hsp27 in regulating Akt activation and cellular apoptosis by mediating interaction between Akt and its upstream activator MK2.

  2. Capturing variations in inundation with satellite remote sensing in a morphologically complex, large lake

    Science.gov (United States)

    Wu, Guiping; Liu, Yuanbo

    2015-04-01

    Poyang Lake is the largest freshwater lake in China, with high morphological complexity from south to north. In recent years, the lake has experienced expansion and shrinkage processes over both short- and long-term scales, resulting in significant hydrological, ecological and economic problems. Exactly how and how rapidly the processes of spatial change have occurred in the lake during the expansion and shrinkage periods is unknown. Such knowledge is of great importance for policymakers as it may help with flood/drought prevention, land use planning and lake ecological conservation. In this study, we investigated the spatial-temporal distribution and changing processes of inundation in Poyang Lake based on Moderate Resolution Imaging Spectroradiometer (MODIS) Level-1B data from 2000 to 2011. A defined water variation rate (WVR) and inundation frequency (IF) indicator revealed the water surface submersion and exposure processes of lake expansion and shrinkage in different zones which were divided according to the lake's hydrological and topographic features. Regional differences and significant seasonality variability were found in the annual and monthly mean IF. The monthly mean IF increased slowly from north to south during January-August but decreased quickly from south to north during September-December. During the lake expansion period, the lake-type water body zone (Zone II) had the fastest expansion rate, with a mean monthly WVR value of 34.47% in February-March, and was followed by the channel-type water body zone (Zone I) in March-May (22.47%). However, during the lake shrinkage period, rapid shrinkage first appeared around the alluvial delta zones in August-October. The sequence of lake surface shrinkage from August to December is exactly opposite to that of lake expansion from February to July. These complex inundation characteristics and changing process were driven by the high temporal variability of the river flows, the morphological diversity of the

  3. Replicating the Ice-Volume Signal of the Early Pleistocene with a Complex Earth System Model

    Science.gov (United States)

    Tabor, C. R.; Poulsen, C. J.; Pollard, D.

    2013-12-01

    Milankovitch theory proposes high-latitude summer insolation intensity paces the ice ages by controlling perennial snow cover amounts (Milankovitch, 1941). According to theory, the ~21 kyr cycle of precession should dominate the ice-volume records since it has the greatest influence on high-latitude summer insolation. Modeling experiments frequently support Milankovitch theory by attributing the majority of Northern Hemisphere high-latitude summer snowmelt to changes in the cycle of precession (e.g. Jackson and Broccoli, 2003). However, ice-volume proxy records, especially those of the Early Pleistocene (2.6-0.8 Ma), display variability with a period of ~41 kyr (Raymo and Lisiecki, 2005), indicative of insolation forcing from obliquity, which has a much smaller influence on summer insolation intensity than precession. Several hypotheses attempt to explain the discrepancies between Milkankovitch theory and the proxy records by invoking phenomena such as insolation gradients (Raymo and Nisancioglu, 2003), hemispheric offset (Raymo et al., 2006; Lee and Poulsen, 2009), and integrated summer energy (Huybers, 2006); however, all of these hypotheses contain caveats (Ruddiman, 2006) and have yet to be supported by modeling studies that use a complex GCM. To explore potential solutions to this '41 kyr problem,' we use an Earth system model composed of the GENESIS GCM and Land Surface model, the BIOME4 vegetation model, and the Pennsylvania State ice-sheet model. Using an asynchronous coupling technique, we run four idealized transient combinations of obliquity and precession, representing the orbital extremes of the Pleistocene (Berger and Loutre, 1991). Each experiment is run through several complete orbital cycles with a dynamic ice domain spanning North America and Greenland, and fixed preindustrial greenhouse-gas concentrations. For all orbital configurations, model results produce greater ice-volume spectral power at the frequency of obliquity despite significantly

  4. Resveratrol upregulates Egr-1 expression and activity involving extracellular signal-regulated protein kinase and ternary complex factors

    Energy Technology Data Exchange (ETDEWEB)

    Rössler, Oliver G.; Glatzel, Daniel; Thiel, Gerald, E-mail: gerald.thiel@uks.eu

    2015-03-01

    Many intracellular functions have been attributed to resveratrol, a polyphenolic phytoalexin found in grapes and in other plants. Here, we show that resveratrol induces the expression of the transcription factor Egr-1 in human embryonic kidney cells. Using a chromosomally embedded Egr-1-responsive reporter gene, we show that the Egr-1 activity was significantly elevated in resveratrol-treated cells, indicating that the newly synthesized Egr-1 protein was biologically active. Stimulus-transcription coupling leading to the resveratrol-induced upregulation of Egr-1 expression and activity requires the protein kinases Raf and extracellular signal-regulated protein kinase ERK, while MAP kinase phosphatase-1 functions as a nuclear shut-off device that interrupts the signaling cascade connecting resveratrol stimulation with enhanced Egr-1 expression. On the transcriptional level, Elk-1, a key transcriptional regulator of serum response element-driven gene transcription, connects the intracellular signaling cascade elicited by resveratrol with transcription of the Egr-1 gene. These data were corroborated by the observation that stimulation of the cells with resveratrol increased the transcriptional activation potential of Elk-1. The SRE as well as the GC-rich DNA binding site of Egr-1 function as resveratrol-responsive elements. Thus, resveratrol regulates gene transcription via activation of the stimulus-regulated protein kinases Raf and ERK and the stimulus-responsive transcription factors TCF and Egr-1. - Highlights: • The plant polyphenol resveratrol upregulates Egr-1 expression and activity. • The stimulation of Egr-1 requires the protein kinases ERK and Raf. • Resveratrol treatment upregulates the transcriptional activation potential of Elk-1. • Resveratrol-induced stimulation of Egr-1 requires ternary complex factors. • Two distinct resveratrol-responsive elements were identified.

  5. Resveratrol upregulates Egr-1 expression and activity involving extracellular signal-regulated protein kinase and ternary complex factors

    International Nuclear Information System (INIS)

    Rössler, Oliver G.; Glatzel, Daniel; Thiel, Gerald

    2015-01-01

    Many intracellular functions have been attributed to resveratrol, a polyphenolic phytoalexin found in grapes and in other plants. Here, we show that resveratrol induces the expression of the transcription factor Egr-1 in human embryonic kidney cells. Using a chromosomally embedded Egr-1-responsive reporter gene, we show that the Egr-1 activity was significantly elevated in resveratrol-treated cells, indicating that the newly synthesized Egr-1 protein was biologically active. Stimulus-transcription coupling leading to the resveratrol-induced upregulation of Egr-1 expression and activity requires the protein kinases Raf and extracellular signal-regulated protein kinase ERK, while MAP kinase phosphatase-1 functions as a nuclear shut-off device that interrupts the signaling cascade connecting resveratrol stimulation with enhanced Egr-1 expression. On the transcriptional level, Elk-1, a key transcriptional regulator of serum response element-driven gene transcription, connects the intracellular signaling cascade elicited by resveratrol with transcription of the Egr-1 gene. These data were corroborated by the observation that stimulation of the cells with resveratrol increased the transcriptional activation potential of Elk-1. The SRE as well as the GC-rich DNA binding site of Egr-1 function as resveratrol-responsive elements. Thus, resveratrol regulates gene transcription via activation of the stimulus-regulated protein kinases Raf and ERK and the stimulus-responsive transcription factors TCF and Egr-1. - Highlights: • The plant polyphenol resveratrol upregulates Egr-1 expression and activity. • The stimulation of Egr-1 requires the protein kinases ERK and Raf. • Resveratrol treatment upregulates the transcriptional activation potential of Elk-1. • Resveratrol-induced stimulation of Egr-1 requires ternary complex factors. • Two distinct resveratrol-responsive elements were identified

  6. Unilateral vestibular deafferentation-induced changes in calcium signaling-related molecules in the rat vestibular nuclear complex.

    Science.gov (United States)

    Masumura, Chisako; Horii, Arata; Mitani, Kenji; Kitahara, Tadashi; Uno, Atsuhiko; Kubo, Takeshi

    2007-03-23

    Inquiries into the neurochemical mechanisms of vestibular compensation, a model of lesion-induced neuronal plasticity, reveal the involvement of both voltage-gated Ca(2+) channels (VGCC) and intracellular Ca(2+) signaling. Indeed, our previous microarray analysis showed an up-regulation of some calcium signaling-related genes such as the alpha2 subunit of L-type calcium channels, calcineurin, and plasma membrane Ca(2+) ATPase 1 (PMCA1) in the ipsilateral vestibular nuclear complex (VNC) following unilateral vestibular deafferentation (UVD). To further elucidate the role of calcium signaling-related molecules in vestibular compensation, we used a quantitative real-time polymerase chain reaction (PCR) method to confirm the microarray results and investigated changes in expression of these molecules at various stages of compensation (6 h to 2 weeks after UVD). We also investigated the changes in gene expression during Bechterew's phenomenon and the effects of a calcineurin inhibitor on vestibular compensation. Real-time PCR showed that genes for the alpha2 subunit of VGCC, PMCA2, and calcineurin were transiently up-regulated 6 h after UVD in ipsilateral VNC. A subsequent UVD, which induced Bechterew's phenomenon, reproduced a complete mirror image of the changes in gene expressions of PMCA2 and calcineurin seen in the initial UVD, while the alpha2 subunit of VGCC gene had a trend to increase in VNC ipsilateral to the second lesion. Pre-treatment by FK506, a calcineurin inhibitor, decelerated the vestibular compensation in a dose-dependent manner. Although it is still uncertain whether these changes in gene expression are causally related to the molecular mechanisms of vestibular compensation, this observation suggests that after increasing the Ca(2+) influx into the ipsilateral VNC neurons via up-regulated VGCC, calcineurin may be involved in their synaptic plasticity. Conversely, an up-regulation of PMCA2, a brain-specific Ca(2+) pump, would increase an efflux of Ca

  7. Complex network inference from P300 signals: Decoding brain state under visual stimulus for able-bodied and disabled subjects

    Science.gov (United States)

    Gao, Zhong-Ke; Cai, Qing; Dong, Na; Zhang, Shan-Shan; Bo, Yun; Zhang, Jie

    2016-10-01

    Distinguishing brain cognitive behavior underlying disabled and able-bodied subjects constitutes a challenging problem of significant importance. Complex network has established itself as a powerful tool for exploring functional brain networks, which sheds light on the inner workings of the human brain. Most existing works in constructing brain network focus on phase-synchronization measures between regional neural activities. In contrast, we propose a novel approach for inferring functional networks from P300 event-related potentials by integrating time and frequency domain information extracted from each channel signal, which we show to be efficient in subsequent pattern recognition. In particular, we construct brain network by regarding each channel signal as a node and determining the edges in terms of correlation of the extracted feature vectors. A six-choice P300 paradigm with six different images is used in testing our new approach, involving one able-bodied subject and three disabled subjects suffering from multiple sclerosis, cerebral palsy, traumatic brain and spinal-cord injury, respectively. We then exploit global efficiency, local efficiency and small-world indices from the derived brain networks to assess the network topological structure associated with different target images. The findings suggest that our method allows identifying brain cognitive behaviors related to visual stimulus between able-bodied and disabled subjects.

  8. CDIP1-BAP31 Complex Transduces Apoptotic Signals from Endoplasmic Reticulum to Mitochondria under Endoplasmic Reticulum Stress

    Directory of Open Access Journals (Sweden)

    Takushi Namba

    2013-10-01

    Full Text Available Resolved endoplasmic reticulum (ER stress response is essential for intracellular homeostatic balance, but unsettled ER stress can lead to apoptosis. Here, we show that a proapoptotic p53 target, CDIP1, acts as a key signal transducer of ER-stress-mediated apoptosis. We identify B-cell-receptor-associated protein 31 (BAP31 as an interacting partner of CDIP1. Upon ER stress, CDIP1 is induced and enhances an association with BAP31 at the ER membrane. We also show that CDIP1 binding to BAP31 is required for BAP31 cleavage upon ER stress and for BAP31-Bcl-2 association. The recruitment of Bcl-2 to the BAP31-CDIP1 complex, as well as CDIP1-dependent truncated Bid (tBid and caspase-8 activation, contributes to BAX oligomerization. Genetic knockout of CDIP1 in mice leads to impaired response to ER-stress-mediated apoptosis. Altogether, our data demonstrate that the CDIP1/BAP31-mediated regulation of mitochondrial apoptosis pathway represents a mechanism for establishing an ER-mitochondrial crosstalk for ER-stress-mediated apoptosis signaling.

  9. Large scale hydrogeological modelling of a low-lying complex coastal aquifer system

    DEFF Research Database (Denmark)

    Meyer, Rena

    2018-01-01

    intrusion. In this thesis a new methodological approach was developed to combine 3D numerical groundwater modelling with a detailed geological description and hydrological, geochemical and geophysical data. It was applied to a regional scale saltwater intrusion in order to analyse and quantify...... the groundwater flow dynamics, identify the driving mechanisms that formed the saltwater intrusion to its present extent and to predict its progression in the future. The study area is located in the transboundary region between Southern Denmark and Northern Germany, adjacent to the Wadden Sea. Here, a large-scale...... parametrization schemes that accommodate hydrogeological heterogeneities. Subsequently, density-dependent flow and transport modelling of multiple salt sources was successfully applied to simulate the formation of the saltwater intrusion during the last 4200 years, accounting for historic changes in the hydraulic...

  10. APINetworks Java. A Java approach to the efficient treatment of large-scale complex networks

    Science.gov (United States)

    Muñoz-Caro, Camelia; Niño, Alfonso; Reyes, Sebastián; Castillo, Miriam

    2016-10-01

    We present a new version of the core structural package of our Application Programming Interface, APINetworks, for the treatment of complex networks in arbitrary computational environments. The new version is written in Java and presents several advantages over the previous C++ version: the portability of the Java code, the easiness of object-oriented design implementations, and the simplicity of memory management. In addition, some additional data structures are introduced for storing the sets of nodes and edges. Also, by resorting to the different garbage collectors currently available in the JVM the Java version is much more efficient than the C++ one with respect to memory management. In particular, the G1 collector is the most efficient one because of the parallel execution of G1 and the Java application. Using G1, APINetworks Java outperforms the C++ version and the well-known NetworkX and JGraphT packages in the building and BFS traversal of linear and complete networks. The better memory management of the present version allows for the modeling of much larger networks.

  11. Complex long-distance effects of mutations that confer linezolid resistance in the large ribosomal subunit

    Science.gov (United States)

    Fulle, Simone; Saini, Jagmohan S.; Homeyer, Nadine; Gohlke, Holger

    2015-01-01

    The emergence of multidrug-resistant pathogens will make current antibiotics ineffective. For linezolid, a member of the novel oxazolidinone class of antibiotics, 10 nucleotide mutations in the ribosome have been described conferring resistance. Hypotheses for how these mutations affect antibiotics binding have been derived based on comparative crystallographic studies. However, a detailed description at the atomistic level of how remote mutations exert long-distance effects has remained elusive. Here, we show that the G2032A-C2499A double mutation, located > 10 Å away from the antibiotic, confers linezolid resistance by a complex set of effects that percolate to the binding site. By molecular dynamics simulations and free energy calculations, we identify U2504 and C2452 as spearheads among binding site nucleotides that exert the most immediate effect on linezolid binding. Structural reorganizations within the ribosomal subunit due to the mutations are likely associated with mutually compensating changes in the effective energy. Furthermore, we suggest two main routes of information transfer from the mutation sites to U2504 and C2452. Between these, we observe cross-talk, which suggests that synergistic effects observed for the two mutations arise in an indirect manner. These results should be relevant for the development of oxazolidinone derivatives that are active against linezolid-resistant strains. PMID:26202966

  12. LARGE-SCALE CO MAPS OF THE LUPUS MOLECULAR CLOUD COMPLEX

    International Nuclear Information System (INIS)

    Tothill, N. F. H.; Loehr, A.; Stark, A. A.; Lane, A. P.; Harnett, J. I.; Bourke, T. L.; Myers, P. C.; Parshley, S. C.; Wright, G. A.; Walker, C. K.

    2009-01-01

    Fully sampled degree-scale maps of the 13 CO 2-1 and CO 4-3 transitions toward three members of the Lupus Molecular Cloud Complex-Lupus I, III, and IV-trace the column density and temperature of the molecular gas. Comparison with IR extinction maps from the c2d project requires most of the gas to have a temperature of 8-10 K. Estimates of the cloud mass from 13 CO emission are roughly consistent with most previous estimates, while the line widths are higher, around 2 km s -1 . CO 4-3 emission is found throughout Lupus I, indicating widespread dense gas, and toward Lupus III and IV. Enhanced line widths at the NW end and along the edge of the B 228 ridge in Lupus I, and a coherent velocity gradient across the ridge, are consistent with interaction between the molecular cloud and an expanding H I shell from the Upper-Scorpius subgroup of the Sco-Cen OB Association. Lupus III is dominated by the effects of two HAe/Be stars, and shows no sign of external influence. Slightly warmer gas around the core of Lupus IV and a low line width suggest heating by the Upper-Centaurus-Lupus subgroup of Sco-Cen, without the effects of an H I shell.

  13. Detecting outliers and learning complex structures with large spectroscopic surveys - a case study with APOGEE stars

    Science.gov (United States)

    Reis, Itamar; Poznanski, Dovi; Baron, Dalya; Zasowski, Gail; Shahaf, Sahar

    2018-05-01

    In this work, we apply and expand on a recently introduced outlier detection algorithm that is based on an unsupervised random forest. We use the algorithm to calculate a similarity measure for stellar spectra from the Apache Point Observatory Galactic Evolution Experiment (APOGEE). We show that the similarity measure traces non-trivial physical properties and contains information about complex structures in the data. We use it for visualization and clustering of the data set, and discuss its ability to find groups of highly similar objects, including spectroscopic twins. Using the similarity matrix to search the data set for objects allows us to find objects that are impossible to find using their best-fitting model parameters. This includes extreme objects for which the models fail, and rare objects that are outside the scope of the model. We use the similarity measure to detect outliers in the data set, and find a number of previously unknown Be-type stars, spectroscopic binaries, carbon rich stars, young stars, and a few that we cannot interpret. Our work further demonstrates the potential for scientific discovery when combining machine learning methods with modern survey data.

  14. Klotho Regulates 14-3-3ζ Monomerization and Binding to the ASK1 Signaling Complex in Response to Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Reynolds K Brobey

    Full Text Available The reactive oxygen species (ROS-sensitive apoptosis signal-regulating kinase 1 (ASK1 signaling complex is a key regulator of p38 MAPK activity, a major modulator of stress-associated with aging disorders. We recently reported that the ratio of free ASK1 to the complex-bound ASK1 is significantly decreased in Klotho-responsive manner and that Klotho-deficient tissues have elevated levels of free ASK1 which coincides with increased oxidative stress. Here, we tested the hypothesis that: 1 covalent interactions exist among three identified proteins constituting the ASK1 signaling complex; 2 in normal unstressed cells the ASK1, 14-3-3ζ and thioredoxin (Trx proteins simultaneously engage in a tripartite complex formation; 3 Klotho's stabilizing effect on the complex relied solely on 14-3-3ζ expression and its apparent phosphorylation and dimerization changes. To verify the hypothesis, we performed 14-3-3ζ siRNA knock-down experiments in conjunction with cell-based assays to measure ASK1-client protein interactions in the presence and absence of Klotho, and with or without an oxidant such as rotenone. Our results show that Klotho activity induces posttranslational modifications in the complex targeting 14-3-3ζ monomer/dimer changes to effectively protect against ASK1 oxidation and dissociation. This is the first observation implicating all three proteins constituting the ASK1 signaling complex in close proximity.

  15. Heritability and demographic analyses in the large isolated population of Val Borbera suggest advantages in mapping complex traits genes.

    Directory of Open Access Journals (Sweden)

    Michela Traglia

    2009-10-01

    Full Text Available Isolated populations are a useful resource for mapping complex traits due to shared stable environment, reduced genetic complexity and extended Linkage Disequilibrium (LD compared to the general population. Here we describe a large genetic isolate from the North West Apennines, the mountain range that runs through Italy from the North West Alps to the South.The study involved 1,803 people living in 7 villages of the upper Borbera Valley. For this large population cohort, data from genealogy reconstruction, medical questionnaires, blood, anthropometric and bone status QUS parameters were evaluated. Demographic and epidemiological analyses indicated a substantial genetic component contributing to each trait variation as well as overlapping genetic determinants and family clustering for some traits.The data provide evidence for significant heritability of medical relevant traits that will be important in mapping quantitative traits. We suggest that this population isolate is suitable to identify rare variants associated with complex phenotypes that may be difficult to study in larger but more heterogeneous populations.

  16. Isotopic shifts in chemical exchange systems. 1. Large isotope effects in the complexation of Na+ isotopes by macrocyclic polyethers

    International Nuclear Information System (INIS)

    Knoechel, A.; Wilken, R.D.

    1981-01-01

    The complexation of 24 Na + and 22 Na + by 18 of the most widely used macrocyclic polyethers (crown ethers and monocyclic and bicyclic aminopolyethers) has been investigated in view of possible equilibrium isotope shifts. Solvated salts and polyether complexes were distributed differently into two phases and isotope ratios determined in both phases. Chloroform/water systems were shown to be particularly suitable to the investigations allowing favorable distribution for Na + and 13 of the 18 polyethers employed. With crown ethers 24 Na + enrichment varied from nonsignficant values (for large crown ethers) up to 3.1 +- 0.4% (18-crown-6). In the case of bicyclic aminopolyethers, ligands with cages of optimum size to accommodate Na + showed 24 Na + enrichment between O (nonsignificant) (2.2/sub B/2./sub B/) and 5.2 +- 1.8% (2.2.1). In contrast, for 2.2.2. and its derivatives, being too large for Na + , 22 Na + enrichment varying from O (nonsignificant) (2.2.2.p) up to 5.4 +- 0.5% (2.2.2.) has been observed. These values are remarkably high. They are explained by different bonding in solvate structure and polyether complex by using the theoretical approach of Bigeleisen

  17. Complexity analysis on public transport networks of 97 large- and medium-sized cities in China

    Science.gov (United States)

    Tian, Zhanwei; Zhang, Zhuo; Wang, Hongfei; Ma, Li

    2018-04-01

    The traffic situation in Chinese urban areas is continuing to deteriorate. To make a better planning and designing of the public transport system, it is necessary to make profound research on the structure of urban public transport networks (PTNs). We investigate 97 large- and medium-sized cities’ PTNs in China, construct three types of network models — bus stop network, bus transit network and bus line network, then analyze the structural characteristics of them. It is revealed that bus stop network is small-world and scale-free, bus transit network and bus line network are both small-world. Betweenness centrality of each city’s PTN shows similar distribution pattern, although these networks’ size is various. When classifying cities according to the characteristics of PTNs or economic development level, the results are similar. It means that the development of cities’ economy and transport network has a strong correlation, PTN expands in a certain model with the development of economy.

  18. Complex magnetic properties and large magnetocaloric effects in RCoGe (R=Tb, Dy compounds

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2018-05-01

    Full Text Available Complicated magnetic phase transitions and Large magnetocaloric effects (MCEs in RCoGe (R=Tb, Dy compounds have been reported in this paper. Results show that the TbCoGe compounds have a magnetic phase transition from antiferromagnetic to paramagnetic (AFM-PM at TN∼16 K, which is close to the value reported by neutron diffraction. The DyCoGe compound undergoes complicated phase changes from 2 K up to 300 K. The peak at 10 K displays a phase transition from antiferromagnetic to ferromagnetic (AFM-FM. In particular, a significant ferromagnetic to paramagnetic (FM-PM phase transition was found at the temperature as high as 175 K and the cusp becomes more abrupt with the magnetic field increasing from 0.01 T to 0.1 T. The maximum value of magnetic entropy change of TbCoGe and DyCoGe compounds achieve 14.5 J/kg K and 11.5 J/kg K respectively for a field change of 0-5 T. Additionally, the correspondingly considerable refrigerant capacity value of 260 J/kg and 242 J/kg are also obtained respectively, suggesting that both TbCoGe and DyCoGe compounds could be considered as good candidates for low temperature magnetic refrigerant.

  19. Ambient noise forecasting with a large acoustic array in a complex shallow water environment.

    Science.gov (United States)

    Rogers, Jeffrey S; Wales, Stephen C; Means, Steven L

    2017-11-01

    Forecasting ambient noise levels in the ocean can be a useful way of characterizing the detection performance of sonar systems and projecting bounds on performance into the near future. The assertion is that noise forecasting can be improved with a priori knowledge of source positions coupled with the ability to resolve closely separated sources in bearing. One example of such a system is the large aperture research array located at the South Florida Test Facility. Given radar and Automatic Identification System defined source positions and environmental information, transmission loss (TL) is computed from known source positions to the array. Source levels (SLs) of individual ships are then estimated from computed TL and the pre-determined beam response of the array using a non-negative least squares algorithm. Ambient noise forecasts are formed by projecting the estimated SLs along known ship tracks. Ambient noise forecast estimates are compared to measured beam level data and mean-squared error is computed. A mean squared error as low as 3.5 dB is demonstrated in 30 min forecast estimates when compared to ground truth.

  20. Coupled Finite Volume and Finite Element Method Analysis of a Complex Large-Span Roof Structure

    Science.gov (United States)

    Szafran, J.; Juszczyk, K.; Kamiński, M.

    2017-12-01

    The main goal of this paper is to present coupled Computational Fluid Dynamics and structural analysis for the precise determination of wind impact on internal forces and deformations of structural elements of a longspan roof structure. The Finite Volume Method (FVM) serves for a solution of the fluid flow problem to model the air flow around the structure, whose results are applied in turn as the boundary tractions in the Finite Element Method problem structural solution for the linear elastostatics with small deformations. The first part is carried out with the use of ANSYS 15.0 computer system, whereas the FEM system Robot supports stress analysis in particular roof members. A comparison of the wind pressure distribution throughout the roof surface shows some differences with respect to that available in the engineering designing codes like Eurocode, which deserves separate further numerical studies. Coupling of these two separate numerical techniques appears to be promising in view of future computational models of stochastic nature in large scale structural systems due to the stochastic perturbation method.

  1. Membrane-localized extra-large G proteins and Gbg of the heterotrimeric G proteins form functional complexes engaged in plant immunity in Arabidopsis.

    Science.gov (United States)

    Maruta, Natsumi; Trusov, Yuri; Brenya, Eric; Parekh, Urvi; Botella, José Ramón

    2015-03-01

    In animals, heterotrimeric G proteins, comprising Ga, Gb, and Gg subunits, are molecular switches whose function tightly depends on Ga and Gbg interaction. Intriguingly, in Arabidopsis (Arabidopsis thaliana), multiple defense responses involve Gbg, but not Ga. We report here that the Gbg dimer directly partners with extra-large G proteins (XLGs) to mediate plant immunity. Arabidopsis mutants deficient in XLGs, Gb, and Gg are similarly compromised in several pathogen defense responses, including disease development and production of reactive oxygen species. Genetic analysis of double, triple, and quadruple mutants confirmed that XLGs and Gbg functionally interact in the same defense signaling pathways. In addition, mutations in XLG2 suppressed the seedling lethal and cell death phenotypes of BRASSINOSTEROID INSENSITIVE1-associated receptor kinase1-interacting receptor-like kinase1 mutants in an identical way as reported for Arabidopsis Gb-deficient mutants. Yeast (Saccharomyces cerevisiae) three-hybrid and bimolecular fluorescent complementation assays revealed that XLG2 physically interacts with all three possible Gbg dimers at the plasma membrane. Phylogenetic analysis indicated a close relationship between XLGs and plant Ga subunits, placing the divergence point at the dawn of land plant evolution. Based on these findings, we conclude that XLGs form functional complexes with Gbg dimers, although the mechanism of action of these complexes, including activation/deactivation, must be radically different form the one used by the canonical Ga subunit and are not likely to share the same receptors. Accordingly, XLGs expand the repertoire of heterotrimeric G proteins in plants and reveal a higher level of diversity in heterotrimeric G protein signaling.

  2. Development of the mechanical engineering complex on the basis of the improvement of large and small businesses relations

    Directory of Open Access Journals (Sweden)

    Sokolova Svetlana

    2017-01-01

    Full Text Available Condition, pace and character of the development of the mechanical engineering complex is in many aspects a crucial factor for the social and economic situation of any country. The development of market relations, changes of the conditions of doing business encourage the enterprises to search new managerial methods and to improve the interaction forms. In this respect the display of the peculiarities of the interaction of large machine engineering enterprises and small business in this sphere and also the assessment of the relationship of their development is an important and crucial issue under modern conditions. The most widely spread forms of the cooperation of large scale mechanical engineering enterprises and small businesses of the industry are: outsourcing, franchising, leasing, subcontracting, venture financing, creation of regional forms of the cooperation of large and small firms. However cooperation processes of large scale and small entrepreneurship in Russia are not properly developed. The authors determine the factors hindering the growth of the machine building industry, suggest the recommendations for the development of the large scale enterprises and small business in the industry, substantiate the role of the government in this process. Besides the mechanism of the state support of the development of small business is described.

  3. "Best Practices in Using Large, Complex Samples: The Importance of Using Appropriate Weights and Design Effect Compensation"

    Directory of Open Access Journals (Sweden)

    Jason W. Osborne

    2011-09-01

    Full Text Available Large surveys often use probability sampling in order to obtain representative samples, and these data sets are valuable tools for researchers in all areas of science. Yet many researchers are not formally prepared to appropriately utilize these resources. Indeed, users of one popular dataset were generally found not to have modeled the analyses to take account of the complex sample (Johnson & Elliott, 1998 even when publishing in highly-regarded journals. It is well known that failure to appropriately model the complex sample can substantially bias the results of the analysis. Examples presented in this paper highlight the risk of error of inference and mis-estimation of parameters from failure to analyze these data sets appropriately.

  4. Structural determination of importin alpha in complex with beak and feather disease virus capsid nuclear localization signal

    International Nuclear Information System (INIS)

    Patterson, Edward I.; Dombrovski, Andrew K.; Swarbrick, Crystall M.D.; Raidal, Shane R.; Forwood, Jade K.

    2013-01-01

    Highlights: •Circovirus capsid proteins contain large nuclear localization signals (NLS). •A method of nuclear import has not been elucidated. •Beak and feather disease virus (BFDV) capsid NLS was crystallized with importin α. •The structure showed BFDV NLS binding to the major site of importin α. •Result shows implications for mechanism of nuclear transport for all circoviruses. -- Abstract: Circoviruses represent a rapidly increasing genus of viruses that infect a variety of vertebrates. Replication requires shuttling viral molecules into the host cell nucleus, a process facilitated by capsid-associated protein (Cap). Whilst a nuclear localization signal (NLS) has been shown to mediate nuclear translocation, the mode of nuclear transport remains to be elucidated. To better understand this process, beak and feather disease virus (BFDV) Cap NLS was crystallized with nuclear import receptor importin-α (Impα). Diffraction yielded structural data to 2.9 Å resolution, and the binding site on both Impα and BFDV Cap NLS were well resolved. The binding mechanism for the major site is likely conserved across circoviruses as supported by the similarity of NLSs in circovirus Caps. This finding illuminates a crucial step for infection of host cells by this viral family, and provides a platform for rational drug design against the binding interface

  5. PI3K-AKT-mTOR-Signaling and beyond: the Complex Network in Gastroenteropancreatic Neuroendocrine Neoplasms

    Science.gov (United States)

    Briest, Franziska; Grabowski, Patricia

    2014-01-01

    Gastroenteropancreatic neuroendocrine neoplasms are heterogeneous in their clinical behavior and require therapies specially tailored according to staging, grading, origin and expression of peptide receptors. Despite extensive scientific efforts, the therapy options are still not satisfactory. The main reasons are due to the lack of a broad mechanistic knowledge, an insufficient classification of specific diagnostic sub-groups, and predictive markers. GEP-NEN tumors evade early diagnosis because of slow asymptomatic growth behavior and are frequently not detected until metastasized. How signaling networks contribute to tumor progression and how these networks interact remains unclear in large parts. In this review we summarize the knowledge on the growth factor responsive non-angiogenetic pathways in sporadic GEP-NENs, highlight promising mechanistic research approaches, and describe important therapy targets. PMID:24578720

  6. A Complex Signal

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The removal of Taiwan from the common strategic objectives of the U.S.-Japan alliance could mean much more than a change of wording While U.S.and Japanese top diplomats and defense officials celebrated closer cooperation forged by their annual meeting in

  7. Prior stress promotes the generalization of contextual fear memories: Involvement of the gabaergic signaling within the basolateral amygdala complex.

    Science.gov (United States)

    Bender, C L; Otamendi, A; Calfa, G D; Molina, V A

    2018-04-20

    Fear generalization occurs when a response, previously acquired with a threatening stimulus, is transferred to a similar one. However, it could be maladaptive when stimuli that do not represent a real threat are appraised as dangerous, which is a hallmark of several anxiety disorders. Stress exposure is a major risk factor for the occurrence of anxiety disorders and it is well established that it influences different phases of fear memory; nevertheless, its impact on the generalization of contextual fear memories has been less studied. In the present work, we have characterized the impact of acute restraint stress prior to contextual fear conditioning on the generalization of this fear memory, and the role of the GABAergic signaling within the basolateral amygdala complex (BLA) on the stress modulatory effects. We have found that a single stress exposure promoted the generalization of this memory trace to a different context that was well discriminated in unstressed conditioned animals. Moreover, this effect was dependent on the formation of a contextual associative memory and on the testing order (i.e., conditioning context first vs generalization context first). Furthermore, we observed that increasing GABA-A signaling by intra-BLA midazolam administration prior to the stressful session exposure prevented the generalization of fear memory, whereas intra-BLA administration of the GABA-A antagonist (Bicuculline), prior to fear conditioning, induced the generalization of fear memory in unstressed rats. We concluded that stress exposure, prior to contextual fear conditioning, promotes the generalization of fear memory and that the GABAergic transmission within the BLA has a critical role in this phenomenon. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Planning and Building Qualifiable Embedded Systems: Safety and Risk Properties Assessment for a Large and Complex System with Embedded Subsystems

    Science.gov (United States)

    Silva, N.; Lopes, R.; Barbosa, R.

    2012-01-01

    Systems based on embedded components and applications are today used in all markets. They are planned and developed by all types of institutions with different types of background experience, multidisciplinary teams and all types of capability and maturity levels. Organisational/engineering maturity has an impact on all aspects of the engineering of large and complex systems. An embedded system is a specific computer system designed to perform one or more dedicated functions, usually with real-time constraints. It is generally integrated as part of a more complex device typically composed of specific hardware such as sensors and actuators. This article presents an experimented technique to evaluate the organisation, processes, system and software engineering practices, methods, tools and the planned/produced artefacts themselves, leading towards certification/qualification. The safety and risk assessment of such core and complex systems is explained, described on a step-by- step manner, while presenting the main results and conclusions of the application of the technique to a real case study.

  9. Estrogen/ERα signaling axis participates in osteoblast maturation via upregulating chromosomal and mitochondrial complex gene expressions

    Science.gov (United States)

    Lin, Pei-I; Tai, Yu-Ting; Chan, Wing P.; Lin, Yi-Ling; Liao, Mei-Hsiu; Chen, Ruei-Ming

    2018-01-01

    Estrogen deficiency usually leads to bone loss and osteoporosis in postmenopausal women. Osteoblasts play crucial roles in bone formation. However, osteoblast functions are influenced by mitochondrial bioenergetic conditions. In this study, we investigated the roles of the estrogen and estrogen receptor alpha (ERα) axis in mitochondrial energy metabolism and subsequent osteoblast mineralization. Exposure of rat calvarial osteoblasts to estradiol caused substantial improvements in alkaline phosphatase activities and cell calcification. In parallel, treatment of human osteoblast-like U2OS cells, derived from a female osteosarcoma patient, with estradiol specifically augmented ERα levels. Sequentially, estradiol stimulated translocation of ERα to nuclei in human osteoblasts and induced expressions of genomic respiratory chain complex NDUFA10, UQCRC1, cytochrome c oxidase (COX)8A, COX6A2, COX8C, COX6C, COX6B2, COX412, and ATP12A genes. Concurrently, estradiol stimulated translocation of ERα to mitochondria from the cytoplasm. A bioinformatic search found the existence of four estrogen response elements in the 5’-promoter region of the mitochondrial cox i gene. Interestingly, estradiol induced COX I mRNA and protein expressions in human osteoblasts or rat calvarial osteoblasts. Knocking-down ERα translation concurrently downregulated estradiol-induced COX I mRNA expression. Consequently, exposure to estradiol led to successive increases in the mitochondrial membrane potential, the mitochondrial enzyme activity, and cellular adenosine triphosphate levels. Taken together, this study showed the roles of the estradiol/ERα signaling axis in improving osteoblast maturation through upregulating the mitochondrial bioenergetic system due to induction of definite chromosomal and mitochondrial complex gene expressions. Our results provide novel insights elucidating the roles of the estrogen/ERα alliance in regulating bone formation. PMID:29416685

  10. Structure of the Regulator of G Protein Signaling 8 (RGS8)-Gαq Complex: MOLECULAR BASIS FOR Gα SELECTIVITY.

    Science.gov (United States)

    Taylor, Veronica G; Bommarito, Paige A; Tesmer, John J G

    2016-03-04

    Regulator of G protein signaling (RGS) proteins interact with activated Gα subunits via their RGS domains and accelerate the hydrolysis of GTP. Although the R4 subfamily of RGS proteins generally accepts both Gαi/o and Gαq/11 subunits as substrates, the R7 and R12 subfamilies select against Gαq/11. In contrast, only one RGS protein, RGS2, is known to be selective for Gαq/11. The molecular basis for this selectivity is not clear. Previously, the crystal structure of RGS2 in complex with Gαq revealed a non-canonical interaction that could be due to interfacial differences imposed by RGS2, the Gα subunit, or both. To resolve this ambiguity, the 2.6 Å crystal structure of RGS8, an R4 subfamily member, was determined in complex with Gαq. RGS8 adopts the same pose on Gαq as it does when bound to Gαi3, indicating that the non-canonical interaction of RGS2 with Gαq is due to unique features of RGS2. Based on the RGS8-Gαq structure, residues in RGS8 that contact a unique α-helical domain loop of Gαq were converted to those typically found in R12 subfamily members, and the reverse substitutions were introduced into RGS10, an R12 subfamily member. Although these substitutions perturbed their ability to stimulate GTP hydrolysis, they did not reverse selectivity. Instead, selectivity for Gαq seems more likely determined by whether strong contacts can be maintained between α6 of the RGS domain and Switch III of Gαq, regions of high sequence and conformational diversity in both protein families. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Signal one and two blockade are both critical for non-myeloablative murine HSCT across a major histocompatibility complex barrier.

    Directory of Open Access Journals (Sweden)

    Kia J Langford-Smith

    Full Text Available Non-myeloablative allogeneic haematopoietic stem cell transplantation (HSCT is rarely achievable clinically, except where donor cells have selective advantages. Murine non-myeloablative conditioning regimens have limited clinical success, partly through use of clinically unachievable cell doses or strain combinations permitting allograft acceptance using immunosuppression alone. We found that reducing busulfan conditioning in murine syngeneic HSCT, increases bone marrow (BM:blood SDF-1 ratio and total donor cells homing to BM, but reduces the proportion of donor cells engrafting. Despite this, syngeneic engraftment is achievable with non-myeloablative busulfan (25 mg/kg and higher cell doses induce increased chimerism. Therefore we investigated regimens promoting initial donor cell engraftment in the major histocompatibility complex barrier mismatched CBA to C57BL/6 allo-transplant model. This requires full myeloablation and immunosuppression with non-depleting anti-CD4/CD8 blocking antibodies to achieve engraftment of low cell doses, and rejects with reduced intensity conditioning (≤75 mg/kg busulfan. We compared increased antibody treatment, G-CSF, niche disruption and high cell dose, using reduced intensity busulfan and CD4/8 blockade in this model. Most treatments increased initial donor engraftment, but only addition of co-stimulatory blockade permitted long-term engraftment with reduced intensity or non-myeloablative conditioning, suggesting that signal 1 and 2 T-cell blockade is more important than early BM niche engraftment for transplant success.

  12. Signal one and two blockade are both critical for non-myeloablative murine HSCT across a major histocompatibility complex barrier.

    Science.gov (United States)

    Langford-Smith, Kia J; Sandiford, Zara; Langford-Smith, Alex; Wilkinson, Fiona L; Jones, Simon A; Wraith, J Ed; Wynn, Robert F; Bigger, Brian W

    2013-01-01

    Non-myeloablative allogeneic haematopoietic stem cell transplantation (HSCT) is rarely achievable clinically, except where donor cells have selective advantages. Murine non-myeloablative conditioning regimens have limited clinical success, partly through use of clinically unachievable cell doses or strain combinations permitting allograft acceptance using immunosuppression alone. We found that reducing busulfan conditioning in murine syngeneic HSCT, increases bone marrow (BM):blood SDF-1 ratio and total donor cells homing to BM, but reduces the proportion of donor cells engrafting. Despite this, syngeneic engraftment is achievable with non-myeloablative busulfan (25 mg/kg) and higher cell doses induce increased chimerism. Therefore we investigated regimens promoting initial donor cell engraftment in the major histocompatibility complex barrier mismatched CBA to C57BL/6 allo-transplant model. This requires full myeloablation and immunosuppression with non-depleting anti-CD4/CD8 blocking antibodies to achieve engraftment of low cell doses, and rejects with reduced intensity conditioning (≤75 mg/kg busulfan). We compared increased antibody treatment, G-CSF, niche disruption and high cell dose, using reduced intensity busulfan and CD4/8 blockade in this model. Most treatments increased initial donor engraftment, but only addition of co-stimulatory blockade permitted long-term engraftment with reduced intensity or non-myeloablative conditioning, suggesting that signal 1 and 2 T-cell blockade is more important than early BM niche engraftment for transplant success.

  13. Hippocampal dendritic spines remodeling and fear memory are modulated by GABAergic signaling within the basolateral amygdala complex.

    Science.gov (United States)

    Giachero, Marcelo; Calfa, Gaston D; Molina, Victor A

    2015-05-01

    GABAergic signaling in the basolateral amygdala complex (BLA) plays a crucial role on the modulation of the stress influence on fear memory. Moreover, accumulating evidence suggests that the dorsal hippocampus (DH) is a downstream target of BLA neurons in contextual fear. Given that hippocampal structural plasticity is proposed to provide a substrate for the storage of long-term memories, the main aim of this study is to evaluate the modulation of GABA neurotransmission in the BLA on spine density in the DH following stress on contextual fear learning. The present findings show that prior stressful experience promoted contextual fear memory and enhanced spine density in the DH. Intra-BLA infusion of midazolam, a positive modulator of GABAa sites, prevented the facilitating influence of stress on both fear retention and hippocampal dendritic spine remodeling. Similarly to the stress-induced effects, the blockade of GABAa sites within the BLA ameliorated fear memory emergence and induced structural remodeling in the DH. These findings suggest that GABAergic transmission in BLA modulates the structural changes in DH associated to the influence of stress on fear memory. © 2015 Wiley Periodicals, Inc.

  14. Wnt-5a/Frizzled9 Receptor Signaling through the Gαo-Gβγ Complex Regulates Dendritic Spine Formation*

    Science.gov (United States)

    Ramírez, Valerie T.; Ramos-Fernández, Eva; Henríquez, Juan Pablo; Lorenzo, Alfredo; Inestrosa, Nibaldo C.

    2016-01-01

    Wnt ligands play crucial roles in the development and regulation of synapse structure and function. Specifically, Wnt-5a acts as a secreted growth factor that regulates dendritic spine formation in rodent hippocampal neurons, resulting in postsynaptic development that promotes the clustering of the PSD-95 (postsynaptic density protein 95). Here, we focused on the early events occurring after the interaction between Wnt-5a and its Frizzled receptor at the neuronal cell surface. Additionally, we studied the role of heterotrimeric G proteins in Wnt-5a-dependent synaptic development. We report that FZD9 (Frizzled9), a Wnt receptor related to Williams syndrome, is localized in the postsynaptic region, where it interacts with Wnt-5a. Functionally, FZD9 is required for the Wnt-5a-mediated increase in dendritic spine density. FZD9 forms a precoupled complex with Gαo under basal conditions that dissociates after Wnt-5a stimulation. Accordingly, we found that G protein inhibition abrogates the Wnt-5a-dependent pathway in hippocampal neurons. In particular, the activation of Gαo appears to be a key factor controlling the Wnt-5a-induced dendritic spine density. In addition, we found that Gβγ is required for the Wnt-5a-mediated increase in cytosolic calcium levels and spinogenesis. Our findings reveal that FZD9 and heterotrimeric G proteins regulate Wnt-5a signaling and dendritic spines in cultured hippocampal neurons. PMID:27402827

  15. Redefining the functional roles of the gastrointestinal migrating motor complex and motilin in small bacterial overgrowth and hunger signaling.

    Science.gov (United States)

    Deloose, Eveline; Tack, Jan

    2016-02-15

    During the fasting state the upper gastrointestinal tract exhibits a specific periodic migrating contraction pattern that is known as the migrating motor complex (MMC). Three different phases can be distinguished during the MMC. Phase III of the MMC is the most active of the three and can start either in the stomach or small intestine. Historically this pattern was designated to be the housekeeper of the gut since disturbances in the pattern were associated with small intestinal bacterial overgrowth; however, its role in the involvement of hunger sensations was already hinted in the beginning of the 20th century by both Cannon (Cannon W, Washburn A. Am J Physiol 29: 441-454, 1912) and Carlson (Carlson A. The Control of Hunger in Health and Disease. Chicago, IL: Univ. of Chicago Press, 1916). The discovery of motilin in 1973 shed more light on the control mechanisms of the MMC. Motilin plasma levels fluctuate together with the phases of the MMC and induce phase III contractions with a gastric onset. Recent research suggests that these motilin-induced phase III contractions signal hunger in healthy subjects and that this system is disturbed in morbidly obese patients. This minireview describes the functions of the MMC in the gut and its regulatory role in controlling hunger sensations. Copyright © 2016 the American Physiological Society.

  16. The challenge for genetic epidemiologists: how to analyze large numbers of SNPs in relation to complex diseases.

    Science.gov (United States)

    Heidema, A Geert; Boer, Jolanda M A; Nagelkerke, Nico; Mariman, Edwin C M; van der A, Daphne L; Feskens, Edith J M

    2006-04-21

    Genetic epidemiologists have taken the challenge to identify genetic polymorphisms involved in the development of diseases. Many have collected data on large numbers of genetic markers but are not familiar with available methods to assess their association with complex diseases. Statistical methods have been developed for analyzing the relation between large numbers of genetic and environmental predictors to disease or disease-related variables in genetic association studies. In this commentary we discuss logistic regression analysis, neural networks, including the parameter decreasing method (PDM) and genetic programming optimized neural networks (GPNN) and several non-parametric methods, which include the set association approach, combinatorial partitioning method (CPM), restricted partitioning method (RPM), multifactor dimensionality reduction (MDR) method and the random forests approach. The relative strengths and weaknesses of these methods are highlighted. Logistic regression and neural networks can handle only a limited number of predictor variables, depending on the number of observations in the dataset. Therefore, they are less useful than the non-parametric methods to approach association studies with large numbers of predictor variables. GPNN on the other hand may be a useful approach to select and model important predictors, but its performance to select the important effects in the presence of large numbers of predictors needs to be examined. Both the set association approach and random forests approach are able to handle a large number of predictors and are useful in reducing these predictors to a subset of predictors with an important contribution to disease. The combinatorial methods give more insight in combination patterns for sets of genetic and/or environmental predictor variables that may be related to the outcome variable. As the non-parametric methods have different strengths and weaknesses we conclude that to approach genetic association

  17. Large area double p-i-n heterostructure for signal multiplexing and demultiplexing in the visible range

    International Nuclear Information System (INIS)

    Vieira, M.; Louro, P.; Fernandes, M.; Vieira, M.A.; Fantoni, A.; Barata, M.

    2009-01-01

    Results on the use of a double a-SiC:H p-i-n heterostructure for signal multiplexing and demultiplexing applications in the visible range, are presented. Modulated monochromatic beams together (multiplexing mode), or a single polychromatic beam (demultiplexing mode) impinge in the device and are absorbed, accordingly to their wavelength, giving rise to a time and wavelength dependent electrical field modulation. Red, green and blue pulsed input channels are transmitted together, each one with a specific transmission rate. The combined optical signal is analyzed by reading out, under different applied voltages, the generated photocurrent. Results show that in the multiplexing mode the output signal is balanced by the wavelength and transmission rate of each input channel, keeping the memory of the incoming optical carriers. In the demultiplexing mode the photocurrent is controlled by the applied voltage allowing regaining the transmitted information. An electrical model gives insight into the device operation.

  18. A Framework of Working Across Disciplines in Early Design and R&D of Large Complex Engineered Systems

    Science.gov (United States)

    McGowan, Anna-Maria Rivas; Papalambros, Panos Y.; Baker, Wayne E.

    2015-01-01

    This paper examines four primary methods of working across disciplines during R&D and early design of large-scale complex engineered systems such as aerospace systems. A conceptualized framework, called the Combining System Elements framework, is presented to delineate several aspects of cross-discipline and system integration practice. The framework is derived from a theoretical and empirical analysis of current work practices in actual operational settings and is informed by theories from organization science and engineering. The explanatory framework may be used by teams to clarify assumptions and associated work practices, which may reduce ambiguity in understanding diverse approaches to early systems research, development and design. The framework also highlights that very different engineering results may be obtained depending on work practices, even when the goals for the engineered system are the same.

  19. Large-scale structure of the Taurus molecular complex. II. Analysis of velocity fluctuations and turbulence. III. Methods for turbulence

    International Nuclear Information System (INIS)

    Kleiner, S.C.; Dickman, R.L.

    1985-01-01

    The velocity autocorrelation function (ACF) of observed spectral line centroid fluctuations is noted to effectively reproduce the actual ACF of turbulent gas motions within an interstellar cloud, thereby furnishing a framework for the study of the large scale velocity structure of the Taurus dark cloud complex traced by the present C-13O J = 1-0 observations of this region. The results obtained are discussed in the context of recent suggestions that widely observed correlations between molecular cloud widths and cloud sizes indicate the presence of a continuum of turbulent motions within the dense interstellar medium. Attention is then given to a method for the quantitative study of these turbulent motions, involving the mapping of a source in an optically thin spectral line and studying the spatial correlation properties of the resulting velocity centroid map. 61 references

  20. Analysis of Maneuvering Targets with Complex Motions by Two-Dimensional Product Modified Lv’s Distribution for Quadratic Frequency Modulation Signals

    Directory of Open Access Journals (Sweden)

    Fulong Jing

    2017-06-01

    Full Text Available For targets with complex motion, such as ships fluctuating with oceanic waves and high maneuvering airplanes, azimuth echo signals can be modeled as multicomponent quadratic frequency modulation (QFM signals after migration compensation and phase adjustment. For the QFM signal model, the chirp rate (CR and the quadratic chirp rate (QCR are two important physical quantities, which need to be estimated. For multicomponent QFM signals, the cross terms create a challenge for detection, which needs to be addressed. In this paper, by employing a novel multi-scale parametric symmetric self-correlation function (PSSF and modified scaled Fourier transform (mSFT, an effective parameter estimation algorithm is proposed—referred to as the Two-Dimensional product modified Lv’s distribution (2D-PMLVD—for QFM signals. The 2D-PMLVD is simple and can be easily implemented by using fast Fourier transform (FFT and complex multiplication. These measures are analyzed in the paper, including the principle, the cross term, anti-noise performance, and computational complexity. Compared to the other three representative methods, the 2D-PMLVD can achieve better anti-noise performance. The 2D-PMLVD, which is free of searching and has no identifiability problems, is more suitable for multicomponent situations. Through several simulations and analyses, the effectiveness of the proposed estimation algorithm is verified.

  1. Epstein-Barr virus large tegument protein BPLF1 contributes to innate immune evasion through interference with toll-like receptor signaling.

    Directory of Open Access Journals (Sweden)

    Michiel van Gent

    2014-02-01

    Full Text Available Viral infection triggers an early host response through activation of pattern recognition receptors, including Toll-like receptors (TLR. TLR signaling cascades induce production of type I interferons and proinflammatory cytokines involved in establishing an anti-viral state as well as in orchestrating ensuing adaptive immunity. To allow infection, replication, and persistence, (herpesviruses employ ingenious strategies to evade host immunity. The human gamma-herpesvirus Epstein-Barr virus (EBV is a large, enveloped DNA virus persistently carried by more than 90% of adults worldwide. It is the causative agent of infectious mononucleosis and is associated with several malignant tumors. EBV activates TLRs, including TLR2, TLR3, and TLR9. Interestingly, both the expression of and signaling by TLRs is attenuated during productive EBV infection. Ubiquitination plays an important role in regulating TLR signaling and is controlled by ubiquitin ligases and deubiquitinases (DUBs. The EBV genome encodes three proteins reported to exert in vitro deubiquitinase activity. Using active site-directed probes, we show that one of these putative DUBs, the conserved herpesvirus large tegument protein BPLF1, acts as a functional DUB in EBV-producing B cells. The BPLF1 enzyme is expressed during the late phase of lytic EBV infection and is incorporated into viral particles. The N-terminal part of the large BPLF1 protein contains the catalytic site for DUB activity and suppresses TLR-mediated activation of NF-κB at, or downstream of, the TRAF6 signaling intermediate. A catalytically inactive mutant of this EBV protein did not reduce NF-κB activation, indicating that DUB activity is essential for attenuating TLR signal transduction. Our combined results show that EBV employs deubiquitination of signaling intermediates in the TLR cascade as a mechanism to counteract innate anti-viral immunity of infected hosts.

  2. Assessing the impact of large-scale computing on the size and complexity of first-principles electromagnetic models

    International Nuclear Information System (INIS)

    Miller, E.K.

    1990-01-01

    There is a growing need to determine the electromagnetic performance of increasingly complex systems at ever higher frequencies. The ideal approach would be some appropriate combination of measurement, analysis, and computation so that system design and assessment can be achieved to a needed degree of accuracy at some acceptable cost. Both measurement and computation benefit from the continuing growth in computer power that, since the early 1950s, has increased by a factor of more than a million in speed and storage. For example, a CRAY2 has an effective throughput (not the clock rate) of about 10 11 floating-point operations (FLOPs) per hour compared with the approximate 10 5 provided by the UNIVAC-1. The purpose of this discussion is to illustrate the computational complexity of modeling large (in wavelengths) electromagnetic problems. In particular the author makes the point that simply relying on faster computers for increasing the size and complexity of problems that can be modeled is less effective than might be anticipated from this raw increase in computer throughput. He suggests that rather than depending on faster computers alone, various analytical and numerical alternatives need development for reducing the overall FLOP count required to acquire the information desired. One approach is to decrease the operation count of the basic model computation itself, by reducing the order of the frequency dependence of the various numerical operations or their multiplying coefficients. Another is to decrease the number of model evaluations that are needed, an example being the number of frequency samples required to define a wideband response, by using an auxiliary model of the expected behavior. 11 refs., 5 figs., 2 tabs

  3. Optimal Design of Complex Passive-Damping Systems for Vibration Control of Large Structures: An Energy-to-Peak Approach

    Directory of Open Access Journals (Sweden)

    Francisco Palacios-Quiñonero

    2014-01-01

    Full Text Available We present a new design strategy that makes it possible to synthesize decentralized output-feedback controllers by solving two successive optimization problems with linear matrix inequality (LMI constraints. In the initial LMI optimization problem, two auxiliary elements are computed: a standard state-feedback controller, which can be taken as a reference in the performance assessment, and a matrix that facilitates a proper definition of the main LMI optimization problem. Next, by solving the second optimization problem, the output-feedback controller is obtained. The proposed strategy extends recent results in static output-feedback control and can be applied to design complex passive-damping systems for vibrational control of large structures. More precisely, by taking advantages of the existing link between fully decentralized velocity-feedback controllers and passive linear dampers, advanced active feedback control strategies can be used to design complex passive-damping systems, which combine the simplicity and robustness of passive control systems with the efficiency of active feedback control. To demonstrate the effectiveness of the proposed approach, a passive-damping system for the seismic protection of a five-story building is designed with excellent results.

  4. Ultrahigh Detective Heterogeneous Photosensor Arrays with In-Pixel Signal Boosting Capability for Large-Area and Skin-Compatible Electronics.

    Science.gov (United States)

    Kim, Jaehyun; Kim, Jaekyun; Jo, Sangho; Kang, Jingu; Jo, Jeong-Wan; Lee, Myungwon; Moon, Juhyuk; Yang, Lin; Kim, Myung-Gil; Kim, Yong-Hoon; Park, Sung Kyu

    2016-04-01

    An ultra-thin and large-area skin-compatible heterogeneous organic/metal-oxide photosensor array is demonstrated which is capable of sensing and boosting signals with high detectivity and signal-to-noise ratio. For the realization of ultra-flexible and high-sensitive heterogeneous photosensor arrays on a polyimide substrate having organic sensor arrays and metal-oxide boosting circuitry, solution-processing and room-temperature alternating photochemical conversion routes are applied. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Multiband LTE-A and 4-PAM signals over large-core plastic fibers for in-home networks

    NARCIS (Netherlands)

    Forni, F.; Shi, Y.; van den Boom, H.P.A.; Tangdiongga, E.; Koonen, A.M.J.

    2016-01-01

    This letter presents the transmission of eight standard compliant 64-QAM long term evolution advanced (LTE-A) bands and 1.4 Gb/s 4-pulse amplitude modulation (PAM) signals over 20 m of 1 mm core diameter graded-index polymethyl methacrylate plastic optical fiber. The optical transceiver consists of

  6. Projected [1H,15N]-HMQC-[1H,1H]-NOESY for large molecular systems: application to a 121 kDa protein-DNA complex

    International Nuclear Information System (INIS)

    Galius, Veniamin; Leontiou, Chrysoula; Richmond, Timothy; Wider, Gerhard

    2008-01-01

    We present a projected [ 1 H, 15 N]-HMQC-[ 1 H, 1 H]-NOESY experiment for observation of NOE interactions between amide protons with degenerate 15 N chemical shifts in large molecular systems. The projection is achieved by simultaneous evolution of the multiple quantum coherence of the nitrogen spin and the attached proton spin. In this way NOE signals can be separated from direct-correlation peaks also in spectra with low resolution by fully exploiting both 1 H and 15 N frequency differences, such that sensitivity can be increased by using short maximum evolution times. The sensitivity of the experiment is not dependent on the projection angle for projections up to 45 deg. and no additional pulses or delays are required as compared to the conventional 2D [ 1 H, 15 N]-HMQC-NOESY. The experiment provides two distinct 2D spectra corresponding to the positive and negative angle projections, respectively. With a linear combination of 1D cross-sections from the two projections the unavoidable sensitivity loss in projection spectra can be compensated for each particular NOE interaction. We demonstrate the application of the novel projection experiment for the observation of an NOE interaction between two sequential glycines with degenerate 15 N chemical shifts in a 121.3 kDa complex of the linker H1 histone protein with a 152 bp linear DNA

  7. A large-scale RF-based Indoor Localization System Using Low-complexity Gaussian filter and improved Bayesian inference

    Directory of Open Access Journals (Sweden)

    L. Xiao

    2013-04-01

    Full Text Available The growing convergence among mobile computing device and smart sensors boosts the development of ubiquitous computing and smart spaces, where localization is an essential part to realize the big vision. The general localization methods based on GPS and cellular techniques are not suitable for tracking numerous small size and limited power objects in the indoor case. In this paper, we propose and demonstrate a new localization method, this method is an easy-setup and cost-effective indoor localization system based on off-the-shelf active RFID technology. Our system is not only compatible with the future smart spaces and ubiquitous computing systems, but also suitable for large-scale indoor localization. The use of low-complexity Gaussian Filter (GF, Wheel Graph Model (WGM and Probabilistic Localization Algorithm (PLA make the proposed algorithm robust and suitable for large-scale indoor positioning from uncertainty, self-adjective to varying indoor environment. Using MATLAB simulation, we study the system performances, especially the dependence on a number of system and environment parameters, and their statistical properties. The simulation results prove that our proposed system is an accurate and cost-effective candidate for indoor localization.

  8. Formation and biochemical characterization of tube/pelle death domain complexes: critical regulators of postreceptor signaling by the Drosophila toll receptor.

    Science.gov (United States)

    Schiffmann, D A; White, J H; Cooper, A; Nutley, M A; Harding, S E; Jumel, K; Solari, R; Ray, K P; Gay, N J

    1999-09-07

    In Drosophila, the Toll receptor signaling pathway is required for embryonic dorso-ventral patterning and at later developmental stages for innate immune responses. It is thought that dimerization of the receptor by binding of the ligand spätzle causes the formation of a postreceptor activation complex at the cytoplasmic surface of the membrane. Two components of this complex are the adaptor tube and protein kinase pelle. These proteins both have "death domains", protein interaction motifs found in a number of signaling pathways, particularly those involved in apoptotic cell death. It is thought that pelle is bound by tube during formation of the activation complexes, and that this interaction is mediated by the death domains. In this paper, we show using the yeast two-hybrid system that the wild-type tube and pelle death domains bind together. Mutant tube proteins which do not support signaling in the embryo are also unable to bind pelle in the 2-hybrid assay. We have purified proteins corresponding to the death domains of tube and pelle and show that these form corresponding heterodimeric complexes in vitro. Partial proteolysis reveals a smaller core consisting of the minimal death domain sequences. We have studied the tube/pelle interaction with the techniques of surface plasmon resonance, analytical ultracentrifugation and isothermal titration calorimetry. These measurements produce a value of K(d) for the complex of about 0.5 microM.

  9. Development of Quality Assessment Techniques for Large Eddy Simulation of Propulsion and Power Systems in Complex Geometries

    Energy Technology Data Exchange (ETDEWEB)

    Lacaze, Guilhem [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Oefelein, Joseph [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-03-01

    Large-eddy-simulation (LES) is quickly becoming a method of choice for studying complex thermo-physics in a wide range of propulsion and power systems. It provides a means to study coupled turbulent combustion and flow processes in parameter spaces that are unattainable using direct-numerical-simulation (DNS), with a degree of fidelity that can be far more accurate than conventional engineering methods such as the Reynolds-averaged Navier-Stokes (RANS) approx- imation. However, development of predictive LES is complicated by the complex interdependence of different type of errors coming from numerical methods, algorithms, models and boundary con- ditions. On the other hand, control of accuracy has become a critical aspect in the development of predictive LES for design. The objective of this project is to create a framework of metrics aimed at quantifying the quality and accuracy of state-of-the-art LES in a manner that addresses the myriad of competing interdependencies. In a typical simulation cycle, only 20% of the computational time is actually usable. The rest is spent in case preparation, assessment, and validation, because of the lack of guidelines. This work increases confidence in the accuracy of a given solution while min- imizing the time obtaining the solution. The approach facilitates control of the tradeoffs between cost, accuracy, and uncertainties as a function of fidelity and methods employed. The analysis is coupled with advanced Uncertainty Quantification techniques employed to estimate confidence in model predictions and calibrate model's parameters. This work has provided positive conse- quences on the accuracy of the results delivered by LES and will soon have a broad impact on research supported both by the DOE and elsewhere.

  10. Complex-enhanced chaotic signals with time-delay signature suppression based on vertical-cavity surface-emitting lasers subject to chaotic optical injection

    Science.gov (United States)

    Chen, Jianjun; Duan, Yingni; Zhong, Zhuqiang

    2018-03-01

    A chaotic system is constructed on the basis of vertical-cavity surface-emitting lasers (VCSELs), where a slave VCSEL subject to chaotic optical injection (COI) from a master VCSEL with the external feedback. The complex degree (CD) and time-delay signature (TDS) of chaotic signals generated by this chaotic system are investigated numerically via permutation entropy (PE) and self-correlation function (SF) methods, respectively. The results show that, compared with master VCSEL subject to optical feedback, complex-enhanced chaotic signals with TDS suppression can be achieved for S-VCSEL subject to COI. Meanwhile, the influences of several controllable parameters on the evolution maps of CD of chaotic signals are carefully considered. It is shown that the CD of chaotic signals for S-VCSEL is always higher than that for M-VCSEL due to the CIO effect. The TDS of chaotic signals can be significantly suppressed by choosing the reasonable parameters in this system. Furthermore, TDS suppression and high CD chaos can be obtained simultaneously in the specific parameter ranges. The results confirm that this chaotic system may effectively improve the security of a chaos-based communication scheme.

  11. Joining inventory by parataxonomists with DNA barcoding of a large complex tropical conserved wildland in northwestern Costa Rica.

    Directory of Open Access Journals (Sweden)

    Daniel H Janzen

    Full Text Available BACKGROUND: The many components of conservation through biodiversity development of a large complex tropical wildland, Area de Conservacion Guanacaste (ACG, thrive on knowing what is its biodiversity and natural history. For 32 years a growing team of Costa Rican parataxonomists has conducted biodiversity inventory of ACG caterpillars, their food plants, and their parasitoids. In 2003, DNA barcoding was added to the inventory process. METHODOLOGY/PRINCIPAL FINDINGS: We describe some of the salient consequences for the parataxonomists of barcoding becoming part of a field biodiversity inventory process that has centuries of tradition. From the barcoding results, the parataxonomists, as well as other downstream users, gain a more fine-scale and greater understanding of the specimens they find, rear, photograph, database and deliver. The parataxonomists also need to adjust to collecting more specimens of what appear to be the "same species"--cryptic species that cannot be distinguished by eye or even food plant alone--while having to work with the name changes and taxonomic uncertainty that comes with discovering that what looked like one species may be many. CONCLUSIONS/SIGNIFICANCE: These career parataxonomists, despite their lack of formal higher education, have proven very capable of absorbing and working around the additional complexity and requirements for accuracy and detail that are generated by adding barcoding to the field base of the ACG inventory. In the process, they have also gained a greater understanding of the fine details of phylogeny, relatedness, evolution, and species-packing in their own tropical complex ecosytems. There is no reason to view DNA barcoding as incompatible in any way with tropical biodiversity inventory as conducted by parataxonomists. Their year-round on-site inventory effort lends itself well to the sampling patterns and sample sizes needed to build a thorough barcode library. Furthermore, the biological

  12. Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling

    Science.gov (United States)

    Honda, Kenya; Yanai, Hideyuki; Mizutani, Tatsuaki; Negishi, Hideo; Shimada, Naoya; Suzuki, Nobutaka; Ohba, Yusuke; Takaoka, Akinori; Yeh, Wen-Chen; Taniguchi, Tadatsugu

    2004-01-01

    Toll-like receptor (TLR) activation is central to immunity, wherein the activation of the TLR9 subfamily members TLR9 and TLR7 results in the robust induction of type I IFNs (IFN-α/β) by means of the MyD88 adaptor protein. However, it remains unknown how the TLR signal “input” can be processed through MyD88 to “output” the induction of the IFN genes. Here, we demonstrate that the transcription factor IRF-7 interacts with MyD88 to form a complex in the cytoplasm. We provide evidence that this complex also involves IRAK4 and TRAF6 and provides the foundation for the TLR9-dependent activation of the IFN genes. The complex defined in this study represents an example of how the coupling of the signaling adaptor and effector kinase molecules together with the transcription factor regulate the processing of an extracellular signal to evoke its versatile downstream transcriptional events in a cell. Thus, we propose that this molecular complex may function as a cytoplasmic transductional-transcriptional processor. PMID:15492225

  13. Seasonal Dynamics of Dissolved Organic Carbon Under Complex Circulation Schemes on a Large Continental Shelf: The Northern South China Sea

    Science.gov (United States)

    Meng, Feifei; Dai, Minhan; Cao, Zhimian; Wu, Kai; Zhao, Xiaozheng; Li, Xiaolin; Chen, Junhui; Gan, Jianping

    2017-12-01

    We examined the distribution and seasonality of dissolved organic carbon (DOC) based on a large data set collected from the northern South China Sea (NSCS) shelf under complex circulation schemes influenced by river plume, coastal upwelling, and downwelling. The highest surface values of ˜117 μmol L-1 were observed nearshore in summer suggesting high DOC supplies from the river inputs, whereas the lowest surface values of ˜62 μmol L-1 were on the outer shelf in winter due to entrainment of DOC-poor subsurface water under strengthened vertical mixing. While the summer coastal upwelling brought lower DOC from offshore depth to the nearshore surface, the winter coastal downwelling delivered higher surface DOC to the midshelf deep waters from the inner shelf fueled by the China Coastal Current (CCC) transporting relatively high DOC from the East China Sea to the NSCS. The intensified winter downwelling generated a cross-shelf DOC transport of 3.1 × 1012 g C over a large shelf area, which induced a significant depression of the NSCS DOC inventory in winter relative to in autumn. In addition to the variable physical controls, net biological production of DOC was semiquantified in both the river plume (2.8 ± 3.0 μmol L-1) and coastal upwelling (3.1 ± 1.3 μmol L-1) in summer. We demonstrated that the NSCS shelf had various origins of DOC including riverine inputs, inter-shelf transport and in situ production. Via cross-shelf transport, the accumulated DOC would be exported to and stored in the deep ocean, suggesting that continental shelves are a potentially effective carbon sink.

  14. The E3 ubiquitin ligase protein associated with Myc (Pam) regulates mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling in vivo through N- and C-terminal domains.

    Science.gov (United States)

    Han, Sangyeul; Kim, Sun; Bahl, Samira; Li, Lin; Burande, Clara F; Smith, Nicole; James, Marianne; Beauchamp, Roberta L; Bhide, Pradeep; DiAntonio, Aaron; Ramesh, Vijaya

    2012-08-31

    Pam and its homologs (the PHR protein family) are large E3 ubiquitin ligases that function to regulate synapse formation and growth in mammals, zebrafish, Drosophila, and Caenorhabditis elegans. Phr1-deficient mouse models (Phr1(Δ8,9) and Phr1(Magellan), with deletions in the N-terminal putative guanine exchange factor region and the C-terminal ubiquitin ligase region, respectively) exhibit axon guidance/outgrowth defects and striking defects of major axon tracts in the CNS. Our earlier studies identified Pam to be associated with tuberous sclerosis complex (TSC) proteins, ubiquitinating TSC2 and regulating mammalian/mechanistic target of rapamycin (mTOR) signaling. Here, we examine the potential involvement of the TSC/mTOR complex 1(mTORC1) signaling pathway in Phr1-deficient mouse models. We observed attenuation of mTORC1 signaling in the brains of both Phr1(Δ8,9) and Phr1(Magellan) mouse models. Our results establish that Pam regulates TSC/mTOR signaling in vitro and in vivo through two distinct domains. To further address whether Pam regulates mTORC1 through two functionally independent domains, we undertook heterozygous mutant crossing between Phr1(Δ8,9) and Phr1(Magellan) mice to generate a compound heterozygous model to determine whether these two domains can complement each other. mTORC1 signaling was not attenuated in the brains of double mutants (Phr1(Δ8,9/Mag)), confirming that Pam displays dual regulation of the mTORC1 pathway through two functional domains. Our results also suggest that although dysregulation of mTORC1 signaling may be responsible for the corpus callosum defects, other neurodevelopmental defects observed with Phr1 deficiency are independent of mTORC1 signaling. The ubiquitin ligase complex containing Pam-Fbxo45 likely targets additional synaptic and axonal proteins, which may explain the overlapping neurodevelopmental defects observed in Phr1 and Fbxo45 deficiency.

  15. SPITZER VIEW OF YOUNG MASSIVE STARS IN THE LARGE MAGELLANIC CLOUD H II COMPLEXES. II. N 159

    International Nuclear Information System (INIS)

    Chen, C.-H. Rosie; Indebetouw, Remy; Chu, You-Hua; Gruendl, Robert A.; Seale, Jonathan P.; Testor, Gerard; Heitsch, Fabian; Meixner, Margaret; Sewilo, Marta

    2010-01-01

    The H II complex N 159 in the Large Magellanic Cloud is used to study massive star formation in different environments, as it contains three giant molecular clouds (GMCs) that have similar sizes and masses but exhibit different intensities of star formation. We identify candidate massive young stellar objects (YSOs) using infrared photometry, and model their spectral energy distributions to constrain mass and evolutionary state. Good fits are obtained for less evolved Type I, I/II, and II sources. Our analysis suggests that there are massive embedded YSOs in N 159B, a maser source, and several ultracompact H II regions. Massive O-type YSOs are found in GMCs N 159-E and N 159-W, which are associated with ionized gas, i.e., where massive stars formed a few Myr ago. The third GMC, N 159-S, has neither O-type YSOs nor evidence of previous massive star formation. This correlation between current and antecedent formation of massive stars suggests that energy feedback is relevant. We present evidence that N 159-W is forming YSOs spontaneously, while collapse in N 159-E may be triggered. Finally, we compare star formation rates determined from YSO counts with those from integrated Hα and 24 μm luminosities and expected from gas surface densities. Detailed dissection of extragalactic GMCs like the one presented here is key to revealing the physics underlying commonly used star formation scaling laws.

  16. Monitoring unrest in a large silicic caldera, the long Valley-inyo craters volcanic complex in east-central California

    Science.gov (United States)

    Hill, D. P.

    1984-06-01

    Recent patterns of geologic unrest in long Valley caldera in east-central California emphasize that this large, silicic volcanic system and the adjacent, geologically youthful Inyo-Mono Craters volcanic chain are still active and capable of producing locally hazardous volcanic eruptions. A series of four magnitude -6 earthquakes in May 1980 called attention to this current episode of unrest, and subsequent activity has included numerous earthquake swarms in the south moat of the caldera accompanied by inflation of the resurgent dome by more than 50 cm over the last five years. The seismicity associated with this unrest is currently monitored by a network of 31 telemetered seismic stations with an automatic processing system that yelds hypocentral locations and earthquake magnitudes in near-real time. Deformation of the ground is monitored by a) a series of overlapping trilateration networks that provide coverage ranging from annual measurements of regional deformation to daily measurements of deformation local to the active, southern section of the caldera, b) a regional network of level lines surveyed annually, c) a regional network of precise gravity stations occupied annually, d) local, L-shaped level figures surveyed every few months, and e) a network of fourteen borehole tiltmeter clusters (two instruments in each cluster) and a borehole dilatometer, the telemetered signals from which provide continuous data on deformation rates. Additional telemetered data provide continuous information on fluctuations in the local magnetic field, hydrogen gas emission rates at three sites, and water level and temperatures in three wells. Continuous data on disharge rates and temperatures from hot springs and fumaroles are collected by several on-site recorders within the caldera, and samples for liquid and gas chemistry are collected several times per year from selected hot springs and fumaroles.

  17. Dosimetric characterization of hypofractionated Gamma Knife radiosurgery of large or complex brain tumors versus linear accelerator-based treatments.

    Science.gov (United States)

    Dong, Peng; Pérez-Andújar, Angélica; Pinnaduwage, Dilini; Braunstein, Steve; Theodosopoulos, Philip; McDermott, Michael; Sneed, Penny; Ma, Lijun

    2016-12-01

    OBJECTIVE Noninvasive Gamma Knife (GK) platforms, such as the relocatable frame and on-board imaging, have enabled hypofractionated GK radiosurgery of large or complex brain lesions. This study aimed to characterize the dosimetric quality of such treatments against linear accelerator-based delivery systems that include the CyberKnife (CK) and volumetric modulated arc therapy (VMAT). METHODS Ten patients treated with VMAT at the authors' institution for large brain tumors (> 3 cm in maximum diameter) were selected for the study. The median prescription dose was 25 Gy (range 20-30 Gy) in 5 fractions. The median planning target volume (PTV) was 9.57 cm 3 (range 1.94-24.81 cm 3 ). Treatment planning was performed using Eclipse External Beam Planning V11 for VMAT on the Varian TrueBeam system, Multiplan V4.5 for the CyberKnife VSI System, and Leksell GammaPlan V10.2 for the Gamma Knife Perfexion system. The percentage of the PTV receiving at least the prescription dose was normalized to be identical across all platforms for individual cases. The prescription isodose value for the PTV, conformity index, Paddick gradient index, mean and maximum doses for organs at risk, and normal brain dose at variable isodose volumes ranging from the 5-Gy isodose volume (V5) to the 15-Gy isodose volume (V15) were compared for all of the cases. RESULTS The mean Paddick gradient index was 2.6 ± 0.2, 3.2 ± 0.5, and 4.3 ± 1.0 for GK, CK, and VMAT, respectively (p 0.06). The average prescription isodose values were 52% (range 47%-69%), 60% (range 46%-68%), and 88% (range 70%-94%) for GK, CK, and VMAT, respectively, thus producing significant variations in dose hot spots among the 3 platforms. Furthermore, the mean V5 values for GK and CK were similar (p > 0.79) at 71.9 ± 36.2 cm 3 and 73.3 ± 31.8 cm 3 , respectively, both of which were statistically lower (p linear accelerator-based treatments. Such a result supports the use of a large number of isocenters or confocal beams for the

  18. Fading of the Tl signal in LiF: Mg, Cu, P during a large post irradiation period

    International Nuclear Information System (INIS)

    Gonzalez, P.R.; Azorin, J.; Furetta, C.

    2004-01-01

    In this work the obtained results of the study of the fading of the Tl signal in dosemeters of LiF activated with magnesium, copper and phosphorus (LiF:Mg,Cu,P) are presented. The studied dosemeters were LiF: Mg,Cu,P + Ptfe, developed in the ININ, taking like reference to the commercial dosemeter GR200A of Chinese manufacture. In both cases the Tl curve presents four peaks; in LiF: Mg,Cu,P + Ptfe, the peaks of smaller size appear in 359 K, 389 K and 447 K, the main dosimetric peak appears in 486 K; in GR200A, the peaks of smaller size appear in 360 K, 389 K and 445 K; while the main dosimetric peak appears in 487 K. The highest fading shown by the dosemeters of LiF: Mg,Cu,P + Ptfe, it was of 3.07%, value very below the one recommended for dosimetric purposes. While the commercial dosemeters presented a fading until of 6.23%, surpassing with the recommended values. The observed fading, it corresponds to the lost of the Tl signal of the peaks 1 and 2, since the first one disappears few hours after the irradiation, while the peak 2, it disappears completely after 94 days, the peak 3 remained stable during the six months of study, while the peak 4, it showed a slight increment due to the contribution of the dose of natural environmental radiation. (Author)

  19. Tele-operation of the electric power generation and transmission in large complex; Teleoperacao da geracao e transmissao de energia eletrica em complexo de grande porte

    Energy Technology Data Exchange (ETDEWEB)

    Martini, Jose Sidnei Colombo

    1992-07-01

    This work presents the specification and development outstanding aspects of a large supervisory and control power system. The engineering experiment, named SSCH - Hierarchical Supervision and Control System, occurred between 1982 and 1992 at Sao Paulo State and is an industrial automation power system most expressive cases carried out in this decade. More than complex development technical details, important management aspects concerning with large project execution are discussed. The SSCHs special characteristics are its dimension, complexity and realtime network analysis resources, applied to large power systems. (author)

  20. Predictive Big Data Analytics: A Study of Parkinson's Disease Using Large, Complex, Heterogeneous, Incongruent, Multi-Source and Incomplete Observations.

    Science.gov (United States)

    Dinov, Ivo D; Heavner, Ben; Tang, Ming; Glusman, Gustavo; Chard, Kyle; Darcy, Mike; Madduri, Ravi; Pa, Judy; Spino, Cathie; Kesselman, Carl; Foster, Ian; Deutsch, Eric W; Price, Nathan D; Van Horn, John D; Ames, Joseph; Clark, Kristi; Hood, Leroy; Hampstead, Benjamin M; Dauer, William; Toga, Arthur W

    2016-01-01

    A unique archive of Big Data on Parkinson's Disease is collected, managed and disseminated by the Parkinson's Progression Markers Initiative (PPMI). The integration of such complex and heterogeneous Big Data from multiple sources offers unparalleled opportunities to study the early stages of prevalent neurodegenerative processes, track their progression and quickly identify the efficacies of alternative treatments. Many previous human and animal studies have examined the relationship of Parkinson's disease (PD) risk to trauma, genetics, environment, co-morbidities, or life style. The defining characteristics of Big Data-large size, incongruency, incompleteness, complexity, multiplicity of scales, and heterogeneity of information-generating sources-all pose challenges to the classical techniques for data management, processing, visualization and interpretation. We propose, implement, test and validate complementary model-based and model-free approaches for PD classification and prediction. To explore PD risk using Big Data methodology, we jointly processed complex PPMI imaging, genetics, clinical and demographic data. Collective representation of the multi-source data facilitates the aggregation and harmonization of complex data elements. This enables joint modeling of the complete data, leading to the development of Big Data analytics, predictive synthesis, and statistical validation. Using heterogeneous PPMI data, we developed a comprehensive protocol for end-to-end data characterization, manipulation, processing, cleaning, analysis and validation. Specifically, we (i) introduce methods for rebalancing imbalanced cohorts, (ii) utilize a wide spectrum of classification methods to generate consistent and powerful phenotypic predictions, and (iii) generate reproducible machine-learning based classification that enables the reporting of model parameters and diagnostic forecasting based on new data. We evaluated several complementary model-based predictive approaches

  1. Predictive Big Data Analytics: A Study of Parkinson's Disease Using Large, Complex, Heterogeneous, Incongruent, Multi-Source and Incomplete Observations.

    Directory of Open Access Journals (Sweden)

    Ivo D Dinov

    Full Text Available A unique archive of Big Data on Parkinson's Disease is collected, managed and disseminated by the Parkinson's Progression Markers Initiative (PPMI. The integration of such complex and heterogeneous Big Data from multiple sources offers unparalleled opportunities to study the early stages of prevalent neurodegenerative processes, track their progression and quickly identify the efficacies of alternative treatments. Many previous human and animal studies have examined the relationship of Parkinson's disease (PD risk to trauma, genetics, environment, co-morbidities, or life style. The defining characteristics of Big Data-large size, incongruency, incompleteness, complexity, multiplicity of scales, and heterogeneity of information-generating sources-all pose challenges to the classical techniques for data management, processing, visualization and interpretation. We propose, implement, test and validate complementary model-based and model-free approaches for PD classification and prediction. To explore PD risk using Big Data methodology, we jointly processed complex PPMI imaging, genetics, clinical and demographic data.Collective representation of the multi-source data facilitates the aggregation and harmonization of complex data elements. This enables joint modeling of the complete data, leading to the development of Big Data analytics, predictive synthesis, and statistical validation. Using heterogeneous PPMI data, we developed a comprehensive protocol for end-to-end data characterization, manipulation, processing, cleaning, analysis and validation. Specifically, we (i introduce methods for rebalancing imbalanced cohorts, (ii utilize a wide spectrum of classification methods to generate consistent and powerful phenotypic predictions, and (iii generate reproducible machine-learning based classification that enables the reporting of model parameters and diagnostic forecasting based on new data. We evaluated several complementary model

  2. A Complex Interplay between Wnt/β-Catenin Signalling and the Cell Cycle in the Adult Liver

    Directory of Open Access Journals (Sweden)

    Angélique Gougelet

    2012-01-01

    Full Text Available Canonical Wnt signalling, governed by its effector β-catenin, is known for a long time as playing an important role in development, tissue homeostasis, and cancer. In the liver, it was unravelled as both an oncogenic pathway involved in a subset of liver cancers and a physiological signalling identified as the “zonation-keeper” of the quiescent liver lobule. This duality has encouraged to explore the role of canonical Wnt in liver regeneration and liver-cell proliferation mainly using murine genetic models of β-catenin overactivation or inactivation. These studies definitely integrate Wnt signalling within the hepatic network driving regeneration and proliferation. We will review here the current knowledge concerning the mitogenic effect of Wnt, to switch on its specific role in the liver, which is quiescent but with a great capacity to regenerate. The duality of β-catenin signalling, associated both with liver quiescence and liver-cell proliferation, will be brought forward.

  3. A Complex Interplay between Wnt/β-Catenin Signalling and the Cell Cycle in the Adult Liver.

    Science.gov (United States)

    Gougelet, Angélique; Colnot, Sabine

    2012-01-01

    Canonical Wnt signalling, governed by its effector β-catenin, is known for a long time as playing an important role in development, tissue homeostasis, and cancer. In the liver, it was unravelled as both an oncogenic pathway involved in a subset of liver cancers and a physiological signalling identified as the "zonation-keeper" of the quiescent liver lobule. This duality has encouraged to explore the role of canonical Wnt in liver regeneration and liver-cell proliferation mainly using murine genetic models of β-catenin overactivation or inactivation. These studies definitely integrate Wnt signalling within the hepatic network driving regeneration and proliferation. We will review here the current knowledge concerning the mitogenic effect of Wnt, to switch on its specific role in the liver, which is quiescent but with a great capacity to regenerate. The duality of β-catenin signalling, associated both with liver quiescence and liver-cell proliferation, will be brought forward.

  4. Low-complexity R-peak detection in ECG signals : a preliminary step towards ambulatory fetal monitoring

    NARCIS (Netherlands)

    Rooijakkers, M.J.; Rabotti, C.; Bennebroek, M.; Meerbergen, van J.; Mischi, M.

    2011-01-01

    Non-invasive fetal health monitoring during pregnancy has become increasingly important. Recent advances in signal processing technology have enabled fetal monitoring during pregnancy, using abdominal ECG recordings. Ubiquitous ambulatory monitoring for continuous fetal health measurement is however

  5. A new inhibitor of the ?-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling

    OpenAIRE

    Beautrait, Alexandre; Paradis, Justine S.; Zimmerman, Brandon; Giubilaro, Jenna; Nikolajev, Ljiljana; Armando, Sylvain; Kobayashi, Hiroyuki; Yamani, Lama; Namkung, Yoon; Heydenreich, Franziska M.; Khoury, Etienne; Audet, Martin; Roux, Philippe P.; Veprintsev, Dmitry B.; Laporte, St?phane A.

    2017-01-01

    In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, ?-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of ?-arrestin recruitment to the receptor and ?-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecul...

  6. Managing project complexity : A study into adapting early project phases to improve project performance in large engineering projects

    NARCIS (Netherlands)

    Bosch-Rekveldt, M.G.C.

    2011-01-01

    Engineering projects become increasingly more complex and project complexity is assumed to be one of the causes for projects being delivered late and over budget. However, what this project complexity actually comprised of was unclear. To improve the overall project performance, this study focuses

  7. Large Variations of the Raman Signal in the Spectra of Twisted Bilayer Graphene on a BN Substrate.

    Science.gov (United States)

    Kalbac, Martin; Frank, Otakar; Kong, Jing; Sanchez-Yamagishi, Javier; Watanabe, Kenji; Taniguchi, Takashi; Jarillo-Herrero, Pablo; Dresselhaus, Mildred S

    2012-03-15

    We report an unusual enhancement of the Raman signal of the G mode in a twisted graphene bilayer (2-LG) on a hexagonal single-crystalline boron nitride substrate. We used an isotopically engineered 2-LG, where the top layer was composed of (13)C atoms and the bottom layer of (12)C atoms. Consequently, it was possible by Raman spectroscopy to distinguish between the enhancement coming from the top and bottom layers. The enhancement of the G mode was, however, found to be similar for the top and bottom layers, and this enhancement effect was observed only at certain locations on the substrate. The experiment with two different laser excitation energies showed that the location of the enhanced spots is dependent on the laser excitation energy. Therefore our results suggest that the enhancement comes from new states in the electronic structure, which are a consequence of a local specific rotation of the grains in graphene layers.

  8. Statistics of the derivatives of complex signal derived from Riesz transform and its application to pseudo-Stokes vector correlation for speckle displacement measurement

    DEFF Research Database (Denmark)

    Zhang, Shun; Yang, Yi; Hanson, Steen Grüner

    2015-01-01

    for the superiority of the proposed PSVC technique, we study the statistical properties of the spatial derivatives of the complex signal representation generated from the Riesz transform. Under the assumption of a Gaussian random process, a theoretical analysis for the pseudo Stokes vector correlation has been...... provided. Based on these results, we show mathematically that PSVC has a performance advantage over conventional intensity-based correlation technique....

  9. LUBAC-Recruited CYLD and A20 Regulate Gene Activation and Cell Death by Exerting Opposing Effects on Linear Ubiquitin in Signaling Complexes

    Directory of Open Access Journals (Sweden)

    Peter Draber

    2015-12-01

    Full Text Available Ubiquitination and deubiquitination are crucial for assembly and disassembly of signaling complexes. LUBAC-generated linear (M1 ubiquitin is important for signaling via various immune receptors. We show here that the deubiquitinases CYLD and A20, but not OTULIN, are recruited to the TNFR1- and NOD2-associated signaling complexes (TNF-RSC and NOD2-SC, at which they cooperate to limit gene activation. Whereas CYLD recruitment depends on its interaction with LUBAC, but not on LUBAC’s M1-chain-forming capacity, A20 recruitment requires this activity. Intriguingly, CYLD and A20 exert opposing effects on M1 chain stability in the TNF-RSC and NOD2-SC. While CYLD cleaves M1 chains, and thereby sensitizes cells to TNF-induced death, A20 binding to them prevents their removal and, consequently, inhibits cell death. Thus, CYLD and A20 cooperatively restrict gene activation and regulate cell death via their respective activities on M1 chains. Hence, the interplay between LUBAC, M1-ubiquitin, CYLD, and A20 is central for physiological signaling through innate immune receptors.

  10. Rac1 augments Wnt signaling by stimulating β-catenin–lymphoid enhancer factor-1 complex assembly independent of β-catenin nuclear import

    Science.gov (United States)

    Jamieson, Cara; Lui, Christina; Brocardo, Mariana G.; Martino-Echarri, Estefania; Henderson, Beric R.

    2015-01-01

    ABSTRACT β-Catenin transduces the Wnt signaling pathway and its nuclear accumulation leads to gene transactivation and cancer. Rac1 GTPase is known to stimulate β-catenin-dependent transcription of Wnt target genes and we confirmed this activity. Here we tested the recent hypothesis that Rac1 augments Wnt signaling by enhancing β-catenin nuclear import; however, we found that silencing/inhibition or up-regulation of Rac1 had no influence on nuclear accumulation of β-catenin. To better define the role of Rac1, we employed proximity ligation assays (PLA) and discovered that a significant pool of Rac1–β-catenin protein complexes redistribute from the plasma membrane to the nucleus upon Wnt or Rac1 activation. More importantly, active Rac1 was shown to stimulate the formation of nuclear β-catenin–lymphoid enhancer factor 1 (LEF-1) complexes. This regulation required Rac1-dependent phosphorylation of β-catenin at specific serines, which when mutated (S191A and S605A) reduced β-catenin binding to LEF-1 by up to 50%, as revealed by PLA and immunoprecipitation experiments. We propose that Rac1-mediated phosphorylation of β-catenin stimulates Wnt-dependent gene transactivation by enhancing β-catenin–LEF-1 complex assembly, providing new insight into the mechanism of cross-talk between Rac1 and canonical Wnt/β-catenin signaling. PMID:26403202

  11. Investigation of the effects of different carotenoids on the absorption and CD signals of light harvesting 1 complexes

    NARCIS (Netherlands)

    Georgakopoulou, S.; van der Zwan, G.; Olsen, J.D.; Hunter, C.N.; Niederman, R.A.; van Grondelle, R.

    2006-01-01

    Absorption and circular dichroism (CD) spectra of light-harvesting (LH)1 complexes from the purple bacteria Rhodobacter (Rba.) sphaeroides and Rhodospirillum (Rsp.) rubrum are presented. The complexes exhibit very low intensity, highly nonconservative, near-infrared (NIR) CD spectra. Absorption and

  12. Signal complexity and modular organization of the courtship behaviours of two sibling species of wolf spiders (Araneae: Lycosidae).

    Science.gov (United States)

    Chiarle, Alberto; Isaia, Marco

    2013-07-01

    In this study, we compare the courtship behaviours of Pardosa proxima and P. vlijmi, two species of wolf spiders up to now regarded as "ethospecies", by means of motion analysis methodologies. In particular, we investigate the features of the signals, aiming at understanding the evolution of the courtship and its role in species delimitation and speciation processes. In our model, we highlight a modular structure of the behaviours and the presence of recurring units and phases. According to other similar cases concerning animal communication, we observed one highly variable and one stereotyped phase for both species. The stereotyped phase is here regarded as a signal related to species identity or an honest signal linked directly to the quality of the signaler. On the contrary, the variable phase aims to facilitate signal detection and assessment by the female reducing choice costs or errors. Variable phases include cues arisen from Fisherian runaway selection, female sensory exploitation and remaining of past selections. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Ancient Origin of the CARD–Coiled Coil/Bcl10/MALT1-Like Paracaspase Signaling Complex Indicates Unknown Critical Functions

    Directory of Open Access Journals (Sweden)

    Jens Staal

    2018-05-01

    Full Text Available The CARD–coiled coil (CC/Bcl10/MALT1-like paracaspase (CBM signaling complexes composed of a CARD–CC family member (CARD-9, -10, -11, or -14, Bcl10, and the type 1 paracaspase MALT1 (PCASP1 play a pivotal role in immunity, inflammation, and cancer. Targeting MALT1 proteolytic activity is of potential therapeutic interest. However, little is known about the evolutionary origin and the original functions of the CBM complex. Type 1 paracaspases originated before the last common ancestor of planulozoa (bilaterians and cnidarians. Notably in bilaterians, Ecdysozoa (e.g., nematodes and insects lacks Bcl10, whereas other lineages have a Bcl10 homolog. A survey of invertebrate CARD–CC homologs revealed such homologs only in species with Bcl10, indicating an ancient common origin of the entire CBM complex. Furthermore, vertebrate-like Syk/Zap70 tyrosine kinase homologs with the ITAM-binding SH2 domain were only found in invertebrate organisms with CARD–CC/Bcl10, indicating that this pathway might be related to the original function of the CBM complex. Moreover, the type 1 paracaspase sequences from invertebrate organisms that have CARD–CC/Bcl10 are more similar to vertebrate paracaspases. Functional analysis of protein–protein interactions, NF-κB signaling, and CYLD cleavage for selected invertebrate type 1 paracaspase and Bcl10 homologs supports this scenario and indicates an ancient origin of the CARD–CC/Bcl10/paracaspase signaling complex. By contrast, many of the known MALT1-associated activities evolved fairly recently, indicating that unknown functions are at the basis of the protein conservation. As a proof-of-concept, we provide initial evidence for a CBM- and NF-κB-independent neuronal function of the Caenorhabditis elegans type 1 paracaspase malt-1. In conclusion, this study shows how evolutionary insights may point at alternative functions of MALT1.

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

    Science.gov (United States)

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

    2017-12-30

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

  15. HACE1 Negatively Regulates Virus-Triggered Type I IFN Signaling by Impeding the Formation of the MAVS-TRAF3 Complex

    Directory of Open Access Journals (Sweden)

    He-Ting Mao

    2016-05-01

    Full Text Available During virus infection, the cascade signaling pathway that leads to the production of proinflammatory cytokines is controlled at multiple levels to avoid detrimental overreaction. HACE1 has been characterized as an important tumor suppressor. Here, we identified HACE1 as an important negative regulator of virus-triggered type I IFN signaling. Overexpression of HACE1 inhibited Sendai virus- or poly (I:C-induced signaling and resulted in reduced IFNB1 production and enhanced virus replication. Knockdown of HACE1 expression exhibited the opposite effects. Ubiquitin E3 ligase activity of the dead mutant HACE1/C876A had a comparable inhibitory function as WT HACE1, suggesting that the suppressive function of HACE1 on virus-induced signaling is independent of its E3 ligase activity. Further study indicated that HACE1 acted downstream of MAVS and upstream of TBK1. Mechanistic studies showed that HACE1 exerts its inhibitory role on virus-induced signaling by disrupting the MAVS-TRAF3 complex. Therefore, we uncovered a novel function of HACE1 in innate immunity regulation.

  16. Large scale expression changes of genes related to neuronal signaling and developmental processes found in lateral septum of postpartum outbred mice.

    Directory of Open Access Journals (Sweden)

    Brian E Eisinger

    Full Text Available Coordinated gene expression changes across the CNS are required to produce the mammalian maternal phenotype. Lateral septum (LS is a brain region critically involved with aspects of maternal care, and we recently examined gene expression of whole septum (LS and medial septum in selectively bred maternal mice. Here, we expand on the prior study by 1 conducting microarray analysis solely on LS in virgin and postpartum mice, 2 using outbred mice, and 3 evaluating the role of sensory input on gene expression changes. Large scale changes in genes related to neuronal signaling were identified, including four GABAA receptor subunits. Subunits α4 and δ were downregulated in maternal LS, likely reflecting a reduction in the extrasynaptic, neurosteroid-sensitive α4/δ containing receptor subtype. Conversely, subunits ε and θ were increased in maternal LS. Fifteen K+ channel related genes showed altered expression, as did dopamine receptors Drd1a and Drd2 (both downregulated, hypocretin receptor 1 (Hcrtr1, kappa opioid receptor 1 (Oprk1, and transient receptor potential channel 4 (Trpc4. Expression of a large number of genes linked to developmental processes or cell differentiation were also altered in postpartum LS, including chemokine (C-X-C motif ligand 12 (Cxcl12, fatty acid binding protein 7 (Fabp7, plasma membrane proteolipid (Pllp, and suppressor of cytokine signaling 2 (Socs2. Additional genes that are linked to anxiety, such as glutathione reductase (Gsr, exhibited altered expression. Pathway analysis also identified changes in genes related to cyclic nucleotide metabolism, chromatin structure, and the Ras gene family. The sensory presence of pups was found to contribute to the altered expression of a subset of genes across all categories. This study suggests that both large changes in neuronal signaling and the possible terminal differentiation of neuronal and/or glial cells play important roles in producing the maternal state.

  17. Longitudinal course of disease in a large cohort of myositis patients with autoantibodies recognizing the signal recognition particle

    Science.gov (United States)

    Werner, Jessie L.; Albayda, Jemyma; Paik, Julie; Danoff, Sonye K.; Casciola-Rosen, Livia; Christopher-Stine, Lisa; Mammen, Andrew L.

    2016-01-01

    Objective Patients with immune-mediated necrotizing myopathy (IMNM) often have autoantibodies recognizing the signal recognition particle (SRP) or HMG-CoA reductase (HMGCR). Here, we studied a cohort of anti-SRP patients to identify factors associated with disease severity and clinical improvement; we also compared the severity of weakness in those with anti-SRP versus anti-HMGCR autoantibodies. Methods All anti-SRP patients in the Johns Hopkins Myositis Cohort from 2002 to 2015 were included. Longitudinal information regarding proximal muscle strength, creatine kinase (CK) levels, and immunosuppressive therapy were recorded at each visit. Univariate and multivariate multilevel regression models were used to assess prognostic factors influencing recovery. Strength in the anti-SRP patients was compared to strength in 49 previously described anti-HMGCR subjects. Results Data from 37 anti-SRP patients and 380 total clinic visits was analyzed. Younger age at onset was associated with more severe weakness at the first visit (p=0.02) and all subsequent visits (p=0.002). Only 50% of patients reached near-full or full strength after 4 years of treatment and most of these continued to have elevated CK levels. Rituximab appeared to be effective in 13 of 17 anti-SRP patients. Anti-SRP patients were significantly weaker than those with anti-HMGCR autoantibodies (−1.3 strength points, p=0.001). Conclusions Younger age at onset is associated with more severe weakness in anti-SRP myositis. Furthermore, even among anti-SRP patients whose strength improved with immunosuppression, most had ongoing disease activity as demonstrated by elevated CK levels. Finally, anti-SRP patients were significantly weaker than anti-HMGCR patients, providing evidence that these autoantibodies are associated with distinct forms of IMNM. PMID:27111848