Sample records for controlling trigger mechanisms

  1. Adaptively Adjusted Event-Triggering Mechanism on Fault Detection for Networked Control Systems.

    PubMed

    Wang, Yu-Long; Lim, Cheng-Chew; Shi, Peng

    2016-12-08

    This paper studies the problem of adaptively adjusted event-triggering mechanism-based fault detection for a class of discrete-time networked control system (NCS) with applications to aircraft dynamics. By taking into account the fault occurrence detection progress and the fault occurrence probability, and introducing an adaptively adjusted event-triggering parameter, a novel event-triggering mechanism is proposed to achieve the efficient utilization of the communication network bandwidth. Both the sensor-to-control station and the control station-to-actuator network-induced delays are taken into account. The event-triggered sensor and the event-triggered control station are utilized simultaneously to establish new network-based closed-loop models for the NCS subject to faults. Based on the established models, the event-triggered simultaneous design of fault detection filter (FDF) and controller is presented. A new algorithm for handling the adaptively adjusted event-triggering parameter is proposed. Performance analysis verifies the effectiveness of the adaptively adjusted event-triggering mechanism, and the simultaneous design of FDF and controller.

  2. Neural robust stabilization via event-triggering mechanism and adaptive learning technique.

    PubMed

    Wang, Ding; Liu, Derong

    2018-06-01

    The robust control synthesis of continuous-time nonlinear systems with uncertain term is investigated via event-triggering mechanism and adaptive critic learning technique. We mainly focus on combining the event-triggering mechanism with adaptive critic designs, so as to solve the nonlinear robust control problem. This can not only make better use of computation and communication resources, but also conduct controller design from the view of intelligent optimization. Through theoretical analysis, the nonlinear robust stabilization can be achieved by obtaining an event-triggered optimal control law of the nominal system with a newly defined cost function and a certain triggering condition. The adaptive critic technique is employed to facilitate the event-triggered control design, where a neural network is introduced as an approximator of the learning phase. The performance of the event-triggered robust control scheme is validated via simulation studies and comparisons. The present method extends the application domain of both event-triggered control and adaptive critic control to nonlinear systems possessing dynamical uncertainties. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Asynchronous sampled-data approach for event-triggered systems

    NASA Astrophysics Data System (ADS)

    Mahmoud, Magdi S.; Memon, Azhar M.

    2017-11-01

    While aperiodically triggered network control systems save a considerable amount of communication bandwidth, they also pose challenges such as coupling between control and event-condition design, optimisation of the available resources such as control, communication and computation power, and time-delays due to computation and communication network. With this motivation, the paper presents separate designs of control and event-triggering mechanism, thus simplifying the overall analysis, asynchronous linear quadratic Gaussian controller which tackles delays and aperiodic nature of transmissions, and a novel event mechanism which compares the cost of the aperiodic system against a reference periodic implementation. The proposed scheme is simulated on a linearised wind turbine model for pitch angle control and the results show significant improvement against the periodic counterpart.

  4. Simulation study of the mechanisms underlying outbreaks of clinical disease caused by Actinobacillus pleuropneumoniae in finishing pigs.

    PubMed

    Klinkenberg, D; Tobias, T J; Bouma, A; van Leengoed, L A M G; Stegeman, J A

    2014-10-01

    Actinobacillus pleuropneumoniae is a major cause of respiratory disease in pigs. Many farms are endemically infected without apparent disease, but occasionally severe outbreaks of pleuropneumonia occur. To prevent and control these outbreaks without antibiotics, the underlying mechanisms of these outbreaks need to be understood. Outbreaks are probably initiated by a trigger (common risk factor) changing the host-pathogen interaction, but it is unclear whether this trigger causes all cases directly (trigger mechanism), or whether the first case starts a transmission chain inducing disease in the infected contacts (transmission mechanism). The aim of this study was to identify conditions under which these mechanisms could cause A. pleuropneumoniae outbreaks, and to assess means for prevention and control. Outbreaks were first characterised by data from a literature review, defining an average outbreak at 12 weeks of age, affecting 50% of animals within 4 days. Simple mathematical models describing the two mechanisms can reproduce average outbreaks, with two observations supporting the trigger mechanism: (1) disease should be transmitted 50 times faster than supported by literature if there is a transmission chain; and (2) the trigger mechanism is consistent with the absence of reported outbreaks in young pigs as they have not yet been colonised by the bacterium. In conclusion, outbreaks of A. pleuropneumoniae on endemic farms are most likely caused by a trigger inducing pneumonia in already infected pigs, but more evidence is needed to identify optimum preventive interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Development, Integration and Testing of Automated Triggering Circuit for Hybrid DC Circuit Breaker

    NASA Astrophysics Data System (ADS)

    Kanabar, Deven; Roy, Swati; Dodiya, Chiragkumar; Pradhan, Subrata

    2017-04-01

    A novel concept of Hybrid DC circuit breaker having combination of mechanical switch and static switch provides arc-less current commutation into the dump resistor during quench in superconducting magnet operation. The triggering of mechanical and static switches in Hybrid DC breaker can be automatized which can effectively reduce the overall current commutation time of hybrid DC circuit breaker and make the operation independent of opening time of mechanical switch. With this view, a dedicated control circuit (auto-triggering circuit) has been developed which can decide the timing and pulse duration for mechanical switch as well as static switch from the operating parameters. This circuit has been tested with dummy parameters and thereafter integrated with the actual test set up of hybrid DC circuit breaker. This paper deals with the conceptual design of the auto-triggering circuit, its control logic and operation. The test results of Hybrid DC circuit breaker using this circuit have also been discussed.

  6. Perceived Triggers of Asthma: Key to Symptom Perception and Management

    PubMed Central

    Janssens, Thomas; Ritz, Thomas

    2013-01-01

    Adequate asthma management depends on an accurate identification of asthma triggers. A review of the literature on trigger perception in asthma shows that individuals vary in their perception of asthma triggers and that the correlation between self-reported asthma triggers and allergy tests is only modest. In this paper, we provide an overview of psychological mechanisms involved in the process of asthma triggers identification. We identify sources of errors in trigger identification and targets for behavioral interventions that aim to improve the accuracy of asthma trigger identification and thereby enhance asthma control. PMID:23957335

  7. Effect of a weak CW trigger on optical rogue waves in the femtosecond supercontinuum generation.

    PubMed

    Li, Qian; Duan, Xiaoqi

    2015-06-15

    We numerically study the characteristics of optical rogue waves in the femtosecond supercontinuum (SC) generation and use the CW triggering mechanism to control the SC generation. Detailed simulation results show for the first time that a weak CW trigger can manipulate the behaviors of optical rogue waves in the femtosecond SC regime. For the proposed CW triggering technique which requires only wavelength tuning and is a handy approach for the active control of SC, the resultant spectrum can be greatly broadened, and the noise properties of the SC can be significantly improved in terms of both of the coherence and intensity stability.

  8. Secure RFID tag or sensor with self-destruction mechanism upon tampering

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

    Nekoogar, Faranak; Dowla, Farid; Twogood, Richard

    A circuit board anti-tamper mechanism comprises a circuit board having a frangible portion, a trigger having a trigger spring, a trigger arming mechanism actuated by the trigger wherein the trigger arming mechanism is initially non-actuated, a force producing mechanism, a latch providing mechanical communication between the trigger arming mechanism and the force producing mechanism, wherein the latch initially retains the force producing mechanism in a refracted position. Arming pressure applied to the trigger sufficient to overcome the trigger spring force will actuate the trigger arming mechanism, causing the anti-tamper mechanism to be armed. Subsequent tampering with the anti-tamper mechanism resultsmore » in a decrease of pressure on the trigger below the trigger spring force, thereby causing the trigger arming mechanism to actuate the latch, thereby releasing the force producing mechanism to apply force to the frangible portion of the circuit board, thereby breaking the circuit board.« less

  9. Sedimentation as a Control for Large Submarine Landslides: Mechanical Modeling and Analysis of the Santa Barbara Basin

    NASA Astrophysics Data System (ADS)

    Stoecklin, A.; Friedli, B.; Puzrin, A. M.

    2017-11-01

    The volume of submarine landslides is a key controlling factor for their damage potential. Particularly large landslides are found in active sedimentary regions. However, the mechanism controlling their volume, and in particular their thickness, remains unclear. Here we present a mechanism that explains how rapid sedimentation can lead to localized slope failure at a preferential depth and set the conditions for the emergence of large-scale slope-parallel landslides. We account for the contractive shearing behavior of the sediments, which locally accelerates the development of overpressures in the pore fluid, even on very mild slopes. When applied to the Santa Barbara basin, the mechanism offers an explanation for the regional variation in landslide thickness and their sedimentation-controlled recurrence. Although earthquakes are the most likely trigger for these mass movements, our results suggest that the sedimentation process controls the geometry of their source region. The mechanism introduced here is generally applicable and can provide initial conditions for subsequent landslide triggering, runout, and tsunami-source analyses in sedimentary regions.

  10. Data processing device test apparatus and method therefor

    DOEpatents

    Wilcox, Richard Jacob; Mulig, Jason D.; Eppes, David; Bruce, Michael R.; Bruce, Victoria J.; Ring, Rosalinda M.; Cole, Jr., Edward I.; Tangyunyong, Paiboon; Hawkins, Charles F.; Louie, Arnold Y.

    2003-04-08

    A method and apparatus mechanism for testing data processing devices are implemented. The test mechanism isolates critical paths by correlating a scanning microscope image with a selected speed path failure. A trigger signal having a preselected value is generated at the start of each pattern vector. The sweep of the scanning microscope is controlled by a computer, which also receives and processes the image signals returned from the microscope. The value of the trigger signal is correlated with a set of pattern lines being driven on the DUT. The trigger is either asserted or negated depending the detection of a pattern line failure and the particular line that failed. In response to the detection of the particular speed path failure being characterized, and the trigger signal, the control computer overlays a mask on the image of the device under test (DUT). The overlaid image provides a visual correlation of the failure with the structural elements of the DUT at the level of resolution of the microscope itself.

  11. Myofascial trigger points, pain, disability, and sleep quality in individuals with mechanical neck pain.

    PubMed

    Muñoz-Muñoz, Sonsoles; Muñoz-García, María T; Alburquerque-Sendín, Francisco; Arroyo-Morales, Manuel; Fernández-de-las-Peñas, César

    2012-10-01

    The purpose of this study was to investigate the presence of active myofascial trigger points (MTrPs) in a greater number of muscles than previous studies and the relation between the presence of MTrPs, the intensity of pain, disability, and sleep quality in mechanical neck pain. Fifteen patients with mechanical neck pain (80% women) and 12 comparable controls participated. Myofascial trigger points were bilaterally explored in the upper trapezius, splenius capitis, semispinalis capitis, sternocleidomastoid, levator scapulae, and scalene muscles in a blinded design. Myofascial trigger points were considered active if the subject recognized the elicited referred pain as a familiar symptom. Myofascial trigger points were considered latent if the elicited referred pain was not recognized as a symptom. Pain was collected with a numerical pain rate scale (0-10); disability was assessed with Neck Disability Index; and sleep quality, with the Pittsburgh Sleep Quality Index. Patients exhibited a greater disability and worse sleep quality than controls (P < .001). The Pittsburgh Sleep Quality Index score was associated with the worst intensity of pain (r = 0.589; P = .021) and disability (r = 0.552; P = .033). Patients showed a greater (P = .002) number of active MTrPs (mean, 2 ± 2) and similar number (P = .505) of latent MTrPs (1.6 ± 1.4) than controls (latent MTrPs, 1.3 ± 1.4). No significant association between the number of latent or active MTrPs and pain, disability, or sleep quality was found. The referred pain elicited by active MTrPs in the neck and shoulder muscles contributed to symptoms in mechanical neck pain. Patients exhibited higher disability and worse sleep quality than controls. Sleep quality was associated with pain intensity and disability. No association between active MTrPs and the intensity of pain, disability, or sleep quality was found. Copyright © 2012 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

  12. Host Galaxies Of Luminous Z ˜ 0.6 Quasars: Major Mergers Are Not Prevalent At The Highest Agn Luminosities

    NASA Astrophysics Data System (ADS)

    Villforth, Carolin; Hamilton, T.; Pawlik, M. M.; Hewlett, T.; Rowlands, K.; Herbst, H.; Shankar, F.; Fontana, A.; Hamann, F.; Koekemoer, A.; Pforr, J.; Trump, J.; Wuyts, S.

    2017-06-01

    Galaxy interactions are thought to be one of the main triggers of active galactic nuclei (AGN), especially at high luminosities, where the accreted gas mass during the AGN lifetime is substantial. Evidence for a connection between mergers and AGN, however, remains mixed. Possible triggering mechanisms remain particularly poorly understood for luminous AGN, which are thought to require triggering by major mergers, rather than secular processes. We analyse the host galaxies of a sample of 20 optically and X-ray selected luminous AGN (log(Lbol [erg s-1]) > 45) at z ˜ 0.6 using Hubble Space Telescope Wide Field Camera 3 data in the F160W/H band. 15/20 sources have resolved host galaxies. We create a control sample of mock AGN by matching the AGN host galaxies to a control sample of non-AGN galaxies. Visual signs of disturbances are found in about 25 per cent of sources in both the AGN hosts and control galaxies. Using both visual classification and quantitative morphology measures, we show that the levels of disturbance are not enhanced when compared to a matched control sample. We find no signs that major mergers play a dominant role in triggering AGN at high luminosities, suggesting that minor mergers and secular processes dominate AGN triggering up to the highest AGN luminosities. The upper limit on the enhanced fraction of major mergers is ≤20 per cent. While major mergers might increase the incidence of luminous AGN, they are not the prevalent triggering mechanism in the population of unobscured AGN.

  13. Host galaxies of luminous z ˜ 0.6 quasars: major mergers are not prevalent at the highest AGN luminosities

    NASA Astrophysics Data System (ADS)

    Villforth, C.; Hamilton, T.; Pawlik, M. M.; Hewlett, T.; Rowlands, K.; Herbst, H.; Shankar, F.; Fontana, A.; Hamann, F.; Koekemoer, A.; Pforr, J.; Trump, J.; Wuyts, S.

    2017-04-01

    Galaxy interactions are thought to be one of the main triggers of active galactic nuclei (AGN), especially at high luminosities, where the accreted gas mass during the AGN lifetime is substantial. Evidence for a connection between mergers and AGN, however, remains mixed. Possible triggering mechanisms remain particularly poorly understood for luminous AGN, which are thought to require triggering by major mergers, rather than secular processes. We analyse the host galaxies of a sample of 20 optically and X-ray selected luminous AGN (log(Lbol [erg s-1]) > 45) at z ˜ 0.6 using Hubble Space Telescope Wide Field Camera 3 data in the F160W/H band. 15/20 sources have resolved host galaxies. We create a control sample of mock AGN by matching the AGN host galaxies to a control sample of non-AGN galaxies. Visual signs of disturbances are found in about 25 per cent of sources in both the AGN hosts and control galaxies. Using both visual classification and quantitative morphology measures, we show that the levels of disturbance are not enhanced when compared to a matched control sample. We find no signs that major mergers play a dominant role in triggering AGN at high luminosities, suggesting that minor mergers and secular processes dominate AGN triggering up to the highest AGN luminosities. The upper limit on the enhanced fraction of major mergers is ≤20 per cent. While major mergers might increase the incidence of luminous AGN, they are not the prevalent triggering mechanism in the population of unobscured AGN.

  14. Stability of model-based event-triggered control systems: a separation property

    NASA Astrophysics Data System (ADS)

    Hao, Fei; Yu, Hao

    2017-04-01

    To save resource of communication, this paper investigates the model-based event-triggered control systems. Two main problems are considered in this paper. One is, for given plant and model, to design event conditions to guarantee the stability of the systems. The other is to consider the effect of the model matrices on the stability. The results show that the closed-loop systems can be asymptotically stabilised with any model matrices in compact sets if the parameters in the event conditions are within the designed ranges. Then, a separation property of model-based event-triggered control is proposed. Namely, the design of the controller gain and the event condition can be separated from the selection of the model matrices. Based on this property, an adaption mechanism is introduced to the model-based event-triggered control systems, which can further improve the sampling performance. Finally, a numerical example is given to show the efficiency and feasibility of the developed results.

  15. An Overview of Recent Advances in Event-Triggered Consensus of Multiagent Systems.

    PubMed

    Ding, Lei; Han, Qing-Long; Ge, Xiaohua; Zhang, Xian-Ming

    2018-04-01

    Event-triggered consensus of multiagent systems (MASs) has attracted tremendous attention from both theoretical and practical perspectives due to the fact that it enables all agents eventually to reach an agreement upon a common quantity of interest while significantly alleviating utilization of communication and computation resources. This paper aims to provide an overview of recent advances in event-triggered consensus of MASs. First, a basic framework of multiagent event-triggered operational mechanisms is established. Second, representative results and methodologies reported in the literature are reviewed and some in-depth analysis is made on several event-triggered schemes, including event-based sampling schemes, model-based event-triggered schemes, sampled-data-based event-triggered schemes, and self-triggered sampling schemes. Third, two examples are outlined to show applicability of event-triggered consensus in power sharing of microgrids and formation control of multirobot systems, respectively. Finally, some challenging issues on event-triggered consensus are proposed for future research.

  16. [Manual trigger point therapy of shoulder pain : Randomized controlled study of effectiveness].

    PubMed

    Sohns, S; Schnieder, K; Licht, G; von Piekartz, H

    2016-12-01

    Although chronic shoulder pain is highly prevalent and myofascial trigger points (mTrP) are thought to be found in the majority of patients with shoulder complaints, the influence on the pain mechanism remains unclear. There are only very few controlled clinical studies on the effects of manual trigger point compression therapy. This randomized controlled trial (RCT) compared the short-term effects of manual trigger point compression therapy (n = 6) with manual sham therapy (n = 6) in patients with unilateral shoulder pain due to myofascial syndrome (MFS). The measurement data were collected before and after two sessions of therapy. Pressure pain thresholds (PPT) of mTrP and symmetrically located points on the asymptomatic side were measured together with neutral points in order to detect a potential unilateral or generalized hyperalgesia. Additionally, the pain was assessed on a visual analog scale (VAS) at rest and during movement and the neck disability index (NDI) and disabilities of the arm, shoulder and hand (DASH) questionnaires were also completed and evaluated. Both treatment modalities led to a significant improvement; however, the manual trigger point compression therapy was significantly more effective in comparison to sham therapy, as measured by different parameters. The significant improvement of PPT values in the interventional group even at sites that were not directly treated, indicates central mechanisms in pain threshold modulation induced by manual compression therapy. The weaker but still measurable effects of sham therapy might be explained by the sham modality being a hands on technique or by sufficient stimulation of the trigger point region during the diagnostics and PPT measurements.

  17. ? PID output-feedback control under event-triggered protocol

    NASA Astrophysics Data System (ADS)

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

    2018-07-01

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

  18. Mechanical stretch triggers rapid epithelial cell division through Piezo1.

    PubMed

    Gudipaty, S A; Lindblom, J; Loftus, P D; Redd, M J; Edes, K; Davey, C F; Krishnegowda, V; Rosenblatt, J

    2017-03-02

    Despite acting as a barrier for the organs they encase, epithelial cells turn over at some of the fastest rates in the body. However, epithelial cell division must be tightly linked to cell death to preserve barrier function and prevent tumour formation. How does the number of dying cells match those dividing to maintain constant numbers? When epithelial cells become too crowded, they activate the stretch-activated channel Piezo1 to trigger extrusion of cells that later die. However, it is unclear how epithelial cell division is controlled to balance cell death at the steady state. Here we show that mammalian epithelial cell division occurs in regions of low cell density where cells are stretched. By experimentally stretching epithelia, we find that mechanical stretch itself rapidly stimulates cell division through activation of the Piezo1 channel. To stimulate cell division, stretch triggers cells that are paused in early G2 phase to activate calcium-dependent phosphorylation of ERK1/2, thereby activating the cyclin B transcription that is necessary to drive cells into mitosis. Although both epithelial cell division and cell extrusion require Piezo1 at the steady state, the type of mechanical force controls the outcome: stretch induces cell division, whereas crowding induces extrusion. How Piezo1-dependent calcium transients activate two opposing processes may depend on where and how Piezo1 is activated, as it accumulates in different subcellular sites with increasing cell density. In sparse epithelial regions in which cells divide, Piezo1 localizes to the plasma membrane and cytoplasm, whereas in dense regions in which cells extrude, it forms large cytoplasmic aggregates. Because Piezo1 senses both mechanical crowding and stretch, it may act as a homeostatic sensor to control epithelial cell numbers, triggering extrusion and apoptosis in crowded regions and cell division in sparse regions.

  19. A steroid-controlled global switch in sensitivity to apoptosis during Drosophila development.

    PubMed

    Kang, Yunsik; Bashirullah, Arash

    2014-02-01

    Precise control over activation of the apoptotic machinery is critical for development, tissue homeostasis and disease. In Drosophila, the decision to trigger apoptosis--whether in response to developmental cues or to DNA damage--converges on transcription of inhibitor of apoptosis protein (IAP) antagonists reaper, hid and grim. Here we describe a parallel process that regulates the sensitivity to, rather than the execution of, apoptosis. This process establishes developmental windows that are permissive or restrictive for triggering apoptosis, where the status of cells determines their capacity to die. We characterize one switch in the sensitivity to apoptotic triggers, from restrictive to permissive, that occurs during third-instar larval (L3) development. Early L3 animals are highly resistant to induction of apoptosis by expression of IAP-antagonists, DNA-damaging agents and even knockdown of the IAP diap1. This resistance to apoptosis, however, is lost in wandering L3 animals after acquiring a heightened sensitivity to apoptotic triggers. This switch in sensitivity to death activators is mediated by a change in mechanisms available for activating endogenous caspases, from an apoptosome-independent to an apoptosome-dependent pathway. This switch in apoptotic pathways is regulated in a cell-autonomous manner by the steroid hormone ecdysone, through changes in expression of critical pro-, but not anti-, apoptotic genes. This steroid-controlled switch defines a novel, physiologically-regulated, mechanism for controlling sensitivity to apoptosis and provides new insights into the control of apoptosis during development. © 2013 Published by Elsevier Inc.

  20. The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

    PubMed Central

    Friedrich, O.; Reid, M. B.; Van den Berghe, G.; Vanhorebeek, I.; Hermans, G.; Rich, M. M.; Larsson, L.

    2015-01-01

    Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca2+ dysregulation is present through altered Ca2+ homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models. PMID:26133937

  1. Improved emotional conflict control triggered by the processing priority of negative emotion.

    PubMed

    Yang, Qian; Wang, Xiangpeng; Yin, Shouhang; Zhao, Xiaoyue; Tan, Jinfeng; Chen, Antao

    2016-04-18

    The prefrontal cortex is responsible for emotional conflict resolution, and this control mechanism is affected by the emotional valence of distracting stimuli. In the present study, we investigated effects of negative and positive stimuli on emotional conflict control using a face-word Stroop task in combination with functional brain imaging. Emotional conflict was absent in the negative face context, in accordance with the null activation observed in areas regarding emotional face processing (fusiform face area, middle temporal/occipital gyrus). Importantly, these visual areas negatively coupled with the dorsolateral prefrontal cortex (DLPFC). However, the significant emotional conflict was observed in the positive face context, this effect was accompanied by activation in areas associated with emotional face processing, and the default mode network (DMN), here, DLPFC mainly negatively coupled with DMN, rather than visual areas. These results suggested that the conflict control mechanism exerted differently between negative faces and positive faces, it implemented more efficiently in the negative face condition, whereas it is more devoted to inhibiting internal interference in the positive face condition. This study thus provides a plausible mechanism of emotional conflict resolution that the rapid pathway for negative emotion processing efficiently triggers control mechanisms to preventively resolve emotional conflict.

  2. Improved emotional conflict control triggered by the processing priority of negative emotion

    PubMed Central

    Yang, Qian; Wang, Xiangpeng; Yin, Shouhang; Zhao, Xiaoyue; Tan, Jinfeng; Chen, Antao

    2016-01-01

    The prefrontal cortex is responsible for emotional conflict resolution, and this control mechanism is affected by the emotional valence of distracting stimuli. In the present study, we investigated effects of negative and positive stimuli on emotional conflict control using a face-word Stroop task in combination with functional brain imaging. Emotional conflict was absent in the negative face context, in accordance with the null activation observed in areas regarding emotional face processing (fusiform face area, middle temporal/occipital gyrus). Importantly, these visual areas negatively coupled with the dorsolateral prefrontal cortex (DLPFC). However, the significant emotional conflict was observed in the positive face context, this effect was accompanied by activation in areas associated with emotional face processing, and the default mode network (DMN), here, DLPFC mainly negatively coupled with DMN, rather than visual areas. These results suggested that the conflict control mechanism exerted differently between negative faces and positive faces, it implemented more efficiently in the negative face condition, whereas it is more devoted to inhibiting internal interference in the positive face condition. This study thus provides a plausible mechanism of emotional conflict resolution that the rapid pathway for negative emotion processing efficiently triggers control mechanisms to preventively resolve emotional conflict. PMID:27086908

  3. Computation and Communication Evaluation of an Authentication Mechanism for Time-Triggered Networked Control Systems

    PubMed Central

    Martins, Goncalo; Moondra, Arul; Dubey, Abhishek; Bhattacharjee, Anirban; Koutsoukos, Xenofon D.

    2016-01-01

    In modern networked control applications, confidentiality and integrity are important features to address in order to prevent against attacks. Moreover, network control systems are a fundamental part of the communication components of current cyber-physical systems (e.g., automotive communications). Many networked control systems employ Time-Triggered (TT) architectures that provide mechanisms enabling the exchange of precise and synchronous messages. TT systems have computation and communication constraints, and with the aim to enable secure communications in the network, it is important to evaluate the computational and communication overhead of implementing secure communication mechanisms. This paper presents a comprehensive analysis and evaluation of the effects of adding a Hash-based Message Authentication (HMAC) to TT networked control systems. The contributions of the paper include (1) the analysis and experimental validation of the communication overhead, as well as a scalability analysis that utilizes the experimental result for both wired and wireless platforms and (2) an experimental evaluation of the computational overhead of HMAC based on a kernel-level Linux implementation. An automotive application is used as an example, and the results show that it is feasible to implement a secure communication mechanism without interfering with the existing automotive controller execution times. The methods and results of the paper can be used for evaluating the performance impact of security mechanisms and, thus, for the design of secure wired and wireless TT networked control systems. PMID:27463718

  4. Computation and Communication Evaluation of an Authentication Mechanism for Time-Triggered Networked Control Systems.

    PubMed

    Martins, Goncalo; Moondra, Arul; Dubey, Abhishek; Bhattacharjee, Anirban; Koutsoukos, Xenofon D

    2016-07-25

    In modern networked control applications, confidentiality and integrity are important features to address in order to prevent against attacks. Moreover, network control systems are a fundamental part of the communication components of current cyber-physical systems (e.g., automotive communications). Many networked control systems employ Time-Triggered (TT) architectures that provide mechanisms enabling the exchange of precise and synchronous messages. TT systems have computation and communication constraints, and with the aim to enable secure communications in the network, it is important to evaluate the computational and communication overhead of implementing secure communication mechanisms. This paper presents a comprehensive analysis and evaluation of the effects of adding a Hash-based Message Authentication (HMAC) to TT networked control systems. The contributions of the paper include (1) the analysis and experimental validation of the communication overhead, as well as a scalability analysis that utilizes the experimental result for both wired and wireless platforms and (2) an experimental evaluation of the computational overhead of HMAC based on a kernel-level Linux implementation. An automotive application is used as an example, and the results show that it is feasible to implement a secure communication mechanism without interfering with the existing automotive controller execution times. The methods and results of the paper can be used for evaluating the performance impact of security mechanisms and, thus, for the design of secure wired and wireless TT networked control systems.

  5. The trigger mechanism of low-frequency earthquakes on Montserrat

    NASA Astrophysics Data System (ADS)

    Neuberg, J. W.; Tuffen, H.; Collier, L.; Green, D.; Powell, T.; Dingwell, D.

    2006-05-01

    A careful analysis of low-frequency seismic events on Soufrièere Hills volcano, Montserrat, points to a source mechanism that is non-destructive, repetitive, and has a stationary source location. By combining these seismological clues with new field evidence and numerical magma flow modelling, we propose a seismic trigger model which is based on brittle failure of magma in the glass transition. Loss of heat and gas from the magma results in a strong viscosity gradient across a dyke or conduit. This leads to a build-up of shear stress near the conduit wall where magma can rupture in a brittle manner, as field evidence from a rhyolitic dyke demonstrates. This brittle failure provides seismic energy, the majority of which is trapped in the conduit or dyke forming the low-frequency coda of the observed seismic signal. The trigger source location marks the transition from ductile conduit flow to friction-controlled magma ascent. As the trigger mechanism is governed by the depth-dependent magma parameters, the source location remains fixed at a depth where the conditions allow brittle failure. This is reflected in the fixed seismic source locations.

  6. Controls of earthquake faulting style on near field landslide triggering: The role of coseismic slip

    NASA Astrophysics Data System (ADS)

    Tatard, L.; Grasso, J. R.

    2013-06-01

    compare the spatial distributions of seven databases of landslides triggered by Mw=5.6-7.9 earthquakes, using distances normalized by the earthquake fault length. We show that the normalized landslide distance distributions collapse, i.e., the normalized distance distributions overlap whatever the size of the earthquake, separately for the events associated with dip-slip, buried-faulting earthquakes, and surface-faulting earthquakes. The dip-slip earthquakes triggered landslides at larger normalized distances than the oblique-slip event of Loma Prieta. We further identify that the surface-faulting earthquakes of Wenchuan, Chi-Chi, and Kashmir triggered landslides at normalized distances smaller than the ones expected from their Mw ≥ 7.6 magnitudes. These results support a control of the seismic slip (through amplitude, rake, and surface versus buried slip) on the distances at which landslides are triggered. In terms of coseismic landslide management in mountainous areas, our results allow us to propose distances at which 95 and 75% of landslides will be triggered as a function of the earthquake focal mechanism.

  7. Delay times of a LiDAR-guided precision sprayer control system

    USDA-ARS?s Scientific Manuscript database

    Accurate flow control systems in triggering sprays against detected targets are needed for precision variable-rate sprayer development. System delay times due to the laser-sensor data buffer, software operation, and hydraulic-mechanical component response were determined for a control system used fo...

  8. Aperiodic linear networked control considering variable channel delays: application to robots coordination.

    PubMed

    Santos, Carlos; Espinosa, Felipe; Santiso, Enrique; Mazo, Manuel

    2015-05-27

    One of the main challenges in wireless cyber-physical systems is to reduce the load of the communication channel while preserving the control performance. In this way, communication resources are liberated for other applications sharing the channel bandwidth. The main contribution of this work is the design of a remote control solution based on an aperiodic and adaptive triggering mechanism considering the current network delay of multiple robotics units. Working with the actual network delay instead of the maximum one leads to abandoning this conservative assumption, since the triggering condition is fixed depending on the current state of the network. This way, the controller manages the usage of the wireless channel in order to reduce the channel delay and to improve the availability of the communication resources. The communication standard under study is the widespread IEEE 802.11g, whose channel delay is clearly uncertain. First, the adaptive self-triggered control is validated through the TrueTime simulation tool configured for the mentioned WiFi standard. Implementation results applying the aperiodic linear control laws on four P3-DX robots are also included. Both of them demonstrate the advantage of this solution in terms of network accessing and control performance with respect to periodic and non-adaptive self-triggered alternatives.

  9. Photofrin binds to procaspase-3 and mediates photodynamic treatment-triggered methionine oxidation and inactivation of procaspase-3

    PubMed Central

    Hsieh, Y-J; Chien, K-Y; Lin, S-Y; Sabu, S; Hsu, R-M; Chi, L-M; Lyu, P-C; Yu, J-S

    2012-01-01

    Diverse death phenotypes of cancer cells can be induced by Photofrin-mediated photodynamic therapy (PDT), which has a decisive role in eliciting a tumor-specific immunity for long-term tumor control. However, the mechanism(s) underlying this diversity remain elusive. Caspase-3 is a critical factor in determining cell death phenotypes in many physiological settings. Here, we report that Photofrin-PDT can modify and inactivate procaspase-3 in cancer cells. In cells exposed to an external apoptotic trigger, high-dose Photofrin-PDT pretreatment blocked the proteolytic activation of procaspase-3 by its upstream caspase. We generated and purified recombinant procaspase-3-D3A (a mutant without autolysis/autoactivation activity) to explore the underlying mechanism(s). Photofrin could bind directly to procaspase-3-D3A, and Photofrin-PDT-triggered inactivation and modification of procaspase-3-D3A was seen in vitro. Mass spectrometry-based quantitative analysis for post-translational modifications using both 16O/18O- and 14N/15N-labeling strategies revealed that Photofrin-PDT triggered a significant oxidation of procaspase-3-D3A (mainly on Met-27, -39 and -44) in a Photofrin dose-dependent manner, whereas the active site Cys-163 remained largely unmodified. Site-directed mutagenesis experiments further showed that Met-44 has an important role in procaspase-3 activation. Collectively, our results reveal that Met oxidation is a novel mechanism for the Photofrin-PDT-mediated inactivation of procaspase-3, potentially explaining at least some of the complicated cell death phenotypes triggered by PDT. PMID:22785533

  10. Hypertension management: rationale for triple therapy based on mechanisms of action.

    PubMed

    Neutel, Joel M; Smith, David H G

    2013-10-01

    An estimated 25% of patients will require 3 antihypertensive agents to achieve blood pressure (BP) control; combination therapy is thus an important strategy in hypertension treatment. This review discusses the triple-therapy combination of an angiotensin receptor blocker (ARB) or direct renin antagonist (DRI) with a calcium channel blocker (CCB) and a diuretic, with a focus on mechanisms of action. Multiple physiologic pathways contribute to hypertension. Combining antihypertensive agents not only better targets the underlying pathways, but also helps blunt compensatory responses that may be triggered by single-agent therapy. DRIs and ARBs target the renin-angiotensin-aldosterone system (RAAS) at the initial and final steps, respectively, and both classes lower BP by reducing the effects of angiotensin-2; however, ARBs may trigger a compensatory increase in renin activity. Dihydropyridine CCBs target L-type calcium channels and lower BP through potent vasodilation, but can trigger compensatory activation of the sympathetic nervous system (SNS) and RAAS. Thiazide diuretics lower BP initially through sodium depletion and plasma volume reduction, followed by total peripheral resistance reduction, but can also trigger compensatory activation of the SNS and RAAS. The combination of an agent targeting the RAAS with a CCB and diuretic is rational, and triple combinations of valsartan/amlodipine/hydrochlorothiazide, olmesartan/amlodipine/hydrochlorothiazide, and aliskiren/amlodipine/hydrochlorothiazide have demonstrated greater effectiveness compared with their respective dual-component combinations. In addition, single-pill, fixed-dose combinations can address barriers to BP control including clinical inertia and poor adherence. Fixed-dose antihypertensive combination products capitalize on complementary mechanisms of action and have been shown to result in improved BP control. © 2012 John Wiley & Sons Ltd.

  11. Reward favours the prepared: incentive and task-informative cues interact to enhance attentional control

    PubMed Central

    Chiew, Kimberly S.; Braver, Todd S.

    2015-01-01

    The dual mechanisms of control account suggests that cognitive control may be implemented through relatively proactive mechanisms in anticipation of stimulus onset, or through reactive mechanisms, triggered in response to changing stimulus demands. Reward incentives and task-informative cues (signaling the presence/absence of upcoming cognitive demand) have both been found to influence cognitive control in a proactive or preparatory fashion; yet, it is currently unclear whether and how such cue effects interact. We investigated this in two experiments using an adapted flanker paradigm, where task-informative and reward incentive cues were orthogonally manipulated on a trial-by-trial basis. In Experiment 1, results indicated that incentives not only speed RTs, but specifically reduce both interference and facilitation effects when combined with task-informative cues, suggesting enhanced proactive attentional control. Experiment 2 manipulated the timing of incentive cue information, demonstrating that such proactive control effects were only replicated with sufficient time to process the incentive cue (Early Incentive); when incentive signals were presented close to target onset (Late Incentive) the primary effect was a speed-accuracy tradeoff. Together, results suggest that advance cueing may trigger differing control strategies, and that these strategies may critically depend on both the timing – and the motivational incentive – to use such cues. PMID:26322689

  12. INITIATORS AND TRIGGERING CONDITIONS FOR ADAPTIVE AUTOMATION IN ADVANCED SMALL MODULAR REACTORS

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

    Katya L Le Blanc; Johanna h Oxstrand

    It is anticipated that Advanced Small Modular Reactors (AdvSMRs) will employ high degrees of automation. High levels of automation can enhance system performance, but often at the cost of reduced human performance. Automation can lead to human out-of the loop issues, unbalanced workload, complacency, and other problems if it is not designed properly. Researchers have proposed adaptive automation (defined as dynamic or flexible allocation of functions) as a way to get the benefits of higher levels of automation without the human performance costs. Adaptive automation has the potential to balance operator workload and enhance operator situation awareness by allocating functionsmore » to the operators in a way that is sensitive to overall workload and capabilities at the time of operation. However, there still a number of questions regarding how to effectively design adaptive automation to achieve that potential. One of those questions is related to how to initiate (or trigger) a shift in automation in order to provide maximal sensitivity to operator needs without introducing undesirable consequences (such as unpredictable mode changes). Several triggering mechanisms for shifts in adaptive automation have been proposed including: operator initiated, critical events, performance-based, physiological measurement, model-based, and hybrid methods. As part of a larger project to develop design guidance for human-automation collaboration in AdvSMRs, researchers at Idaho National Laboratory have investigated the effectiveness and applicability of each of these triggering mechanisms in the context of AdvSMR. Researchers reviewed the empirical literature on adaptive automation and assessed each triggering mechanism based on the human-system performance consequences of employing that mechanism. Researchers also assessed the practicality and feasibility of using the mechanism in the context of an AdvSMR control room. Results indicate that there are tradeoffs associated with each mechanism, but that some are more applicable to the AdvSMR domain. The two mechanisms that consistently improve performance in laboratory studies are operator initiated adaptive automation based on hierarchical task delegation and the Electroencephalogram(EEG) –based measure of engagement. Current EEG methods are intrusive and require intensive analysis; therefore it is not recommended for an AdvSMR control rooms at this time. Researchers also discuss limitations in the existing empirical literature and make recommendations for further research.« less

  13. Sex, genes, and heat: triggers of diversity.

    PubMed

    Western, P S; Sinclair, A H

    2001-11-01

    In vertebrates, sex is determined by a surprising variety of mechanisms. In many reptiles, the primary testis or ovary-determining trigger is regulated by egg incubation temperature. This temperature dependent sex determining (TSD) mechanism occurs in all crocodilians and marine turtles examined to date and is common in terrestrial turtles and viviparous lizards (Ewert et al. 1994. J Exp Zool 270:3-15; Lang and Andrews. 1994. J Exp Biol 270:28-44; Mrosovsky. 1994. J Exp Zool 270:16-27; Pieau. 1996. Bioessays 18:19-26; Viets et al. 1994. J Exp Zool 270:45-56; Wibbels et al. 1998. J Exp Zool 281:409-416). In contrast, sex in mammals and birds is determined chromosomally (CSD). Despite these differences, morphological development of the gonads in all these vertebrate groups appears to have been conserved through evolution. Therefore, the genetic mechanisms triggering sex determination appear not to have been conserved through evolution, although the basic genetic pathway controlling the morphological differentiation of the gonads appears to have been conserved. Copyright 2001 Wiley-Liss, Inc.

  14. Status of the NectarCAM camera project

    NASA Astrophysics Data System (ADS)

    Glicenstein, J.-F.; Barcelo, M.; Barrio, J.-A.; Blanch, O.; Boix, J.; Bolmont, J.; Boutonnet, C.; Brun, P.; Chabanne, E.; Champion, C.; Colonges, S.; Corona, P.; Courty, B.; Delagnes, E.; Delgado, C.; Diaz, C.; Ernenwein, J.-P.; Fegan, S.; Ferreira, O.; Fesquet, M.; Fontaine, G.; Fouque, N.; Henault, F.; Gascón, D.; Giebels, B.; Herranz, D.; Hermel, R.; Hoffmann, D.; Horan, D.; Houles, J.; Jean, P.; Karkar, S.; Knödlseder, J.; Martinez, G.; Lamanna, G.; LeFlour, T.; Lévêque, A.; Lopez-Coto, R.; Louis, F.; Moudden, Y.; Moulin, E.; Nayman, P.; Nunio, F.; Olive, J.-F.; Panazol, J.-L.; Pavy, S.; Petrucci, P.-O.; Punch, M.; Prast, Julie; Ramon, P.; Rateau, S.; Ribó, M.; Rosier-Lees, S.; Sanuy, A.; Sizun, P.; Sieiro, J.; Sulanke, K.-H.; Tavernet, J.-P.; Tejedor, L. A.; Toussenel, F.; Vasileiadis, G.; Voisin, V.; Waegebert, V.; Zurbach, C.

    2014-07-01

    NectarCAM is a camera designed for the medium-sized telescopes of the Cherenkov Telescope Array (CTA) covering the central energy range 100 GeV to 30 TeV. It has a modular design based on the NECTAr chip, at the heart of which is a GHz sampling Switched Capacitor Array and 12-bit Analog to Digital converter. The camera will be equipped with 265 7-photomultiplier modules, covering a field of view of 7 to 8 degrees. Each module includes the photomultiplier bases, High Voltage supply, pre-amplifier, trigger, readout and Thernet transceiver. Events recorded last between a few nanoseconds and tens of nanoseconds. A flexible trigger scheme allows to read out very long events. NectarCAM can sustain a data rate of 10 kHz. The camera concept, the design and tests of the various subcomponents and results of thermal and electrical prototypes are presented. The design includes the mechanical structure, the cooling of electronics, read-out, clock distribution, slow control, data-acquisition, trigger, monitoring and services. A 133-pixel prototype with full scale mechanics, cooling, data acquisition and slow control will be built at the end of 2014.

  15. Global search of triggered non-volcanic tremor

    NASA Astrophysics Data System (ADS)

    Chao, Tzu-Kai Kevin

    Deep non-volcanic tremor is a newly discovered seismic phenomenon with low amplitude, long duration, and no clear P- and S-waves as compared with regular earthquake. Tremor has been observed at many major plate-boundary faults, providing new information about fault slip behaviors below the seismogenic zone. While tremor mostly occurs spontaneously (ambient tremor) or during episodic slow-slip events (SSEs), sometimes tremor can also be triggered during teleseismic waves of distance earthquakes, which is known as "triggered tremor". The primary focus of my Ph.D. work is to understand the physical mechanisms and necessary conditions of triggered tremor by systematic investigations in different tectonic regions. In the first chapter of my dissertation, I conduct a systematic survey of triggered tremor beneath the Central Range (CR) in Taiwan for 45 teleseismic earthquakes from 1998 to 2009 with Mw ≥ 7.5. Triggered tremors are visually identified as bursts of high-frequency (2-8 Hz), non-impulsive, and long-duration seismic energy that are coherent among many seismic stations and modulated by the teleseismic surface waves. A total of 9 teleseismic earthquakes has triggered clear tremor in Taiwan. The peak ground velocity (PGV) of teleseismic surface waves is the most important factor in determining tremor triggering potential, with an apparent threshold of ˜0.1 cm/s, or 7-8 kPa. However, such threshold is partially controlled by the background noise level, preventing triggered tremor with weaker amplitude from being observed. In addition, I find a positive correlation between the PGV and the triggered tremor amplitude, which is consistent with the prediction of the 'clock-advance' model. This suggests that triggered tremor can be considered as a sped-up occurrence of ambient tremor under fast loading from the passing surface waves. Finally, the incident angles of surface waves also play an important rule in controlling the tremor triggering potential. The next chapter focuses on a systematic comparison of triggered tremor around the Calaveras Fault (CF) in northern California (NC), the Parkfield-Cholame section of the San Andreas Fault (SAF) in central California (CC), and the San Jacinto Fault (SJF) in southern California (SC). Out of 42 large (Mw ≥7.5) earthquakes between 2001 and 2010, only the 2002 Mw 7.9 Denali fault earthquake triggered clear tremor in NC and SC. In comparison, abundant triggered and ambient tremor has been observed in CC. Further analysis reveal that the lack of triggered tremor observations in SC and NC is not simply a consequence of their different background noise levels as compared to CC, but rather reflects different background tremor rates in these regions. In the final chapter, I systematically search for triggered tremor following the 2011 Mw9.0 Tohoku-Oki earthquake in the regions where ambient or triggered tremor has been found before. The main purpose is to check whether triggered tremor is observed in regions when certain conditions (e.g., surface wave amplitudes) are met. Triggered tremor is observed in southwest Japan, Taiwan, the Aleutian Arc, south-central Alaska, northern Vancouver Island, the Parkfield-Cholame section of the SAF in CC and the SJF in SC, and the North Island of New Zealand. Such a widespread triggering of tremor is not too surprising because of the large amplitude surface waves (minimum peak value of ˜0.1 cm/s) and the associated dynamic stresses (at least ˜7-8 kPa), which is one of the most important factors in controlling the triggering threshold. The triggered tremor in different region is located close to or nearby the ambient tremor active area. In addition, the amplitudes of triggered tremor have positive correlations with the amplitudes of teleseismic surface waves among many regions. Moreover, both Love and Rayleigh waves participate in triggering tremor in different regions, and their triggering potential is somewhat controlled by the incident angles. In summary, systematically surveys of triggered tremor in different tectonic regions reveal that triggered tremor shares similar physical mechanism (shear failure on the fault interface) as ambient tremor but with different loading conditions. The amplitude of the teleseismic surface wave is one of the most important factors in controlling the tremor triggering threshold. In addition, the frequency contents and incident angles of the triggering waves, and local fault geometry and ambient conditions also play certain roles in determining the triggering potential. On the other hand, the background noise level and seismic network coverage and station quality also could affect the apparent triggering threshold. (Abstract shortened by UMI.).

  16. Respirator triggering of electron-beam computed tomography (EBCT): differences in dynamic changes between augmented ventilation and controlled mechanical ventilation

    NASA Astrophysics Data System (ADS)

    Recheis, Wolfgang A.; Kleinsasser, Axel; Schuster, Antonius H.; Loeckinger, Alexander; Frede, Thomas; Springer, Peter; Hoermann, Christoph; zur Nedden, Dieter

    2000-04-01

    The purpose was to evaluate differences in dynamic changes of the lung aeration (air-tissue ratio) between augmented modes of ventilation (AMV) and controlled mechanical ventilation (CMV) in normal subjects. 4 volunteers, ventilated with the different respirator protocols via face mask, were scanned using the EBCT in the 50 ms mode. A software analyzed the respirator's digitized pressure and volume signals of two subsequent ventilation phases. Using these values it was possible to calculate the onset of inspiration or expiration of the next respiratory phase. The calculated starting point was then used to trigger the EBCT. The dynamic changes of air- tissue ratios were evaluated in three separate regions: a ventral, an intermediate and a dorsal area. AMV results in increase of air-tissue ratio in the dorsal lung area due to the active contraction of the diaphragm, whereas CMV results in a more pronounced increase in air-tissue ratio of the ventral lung area. This study gives further insight into the dynamic changes of the lung's biomechanics by comparing augmented ventilation and controlled mechanical ventilation in the healthy proband.

  17. PLK4 trans-Autoactivation Controls Centriole Biogenesis in Space.

    PubMed

    Lopes, Carla A M; Jana, Swadhin Chandra; Cunha-Ferreira, Inês; Zitouni, Sihem; Bento, Inês; Duarte, Paulo; Gilberto, Samuel; Freixo, Francisco; Guerrero, Adán; Francia, Maria; Lince-Faria, Mariana; Carneiro, Jorge; Bettencourt-Dias, Mónica

    2015-10-26

    Centrioles are essential for cilia and centrosome assembly. In centriole-containing cells, centrioles always form juxtaposed to pre-existing ones, motivating a century-old debate on centriole biogenesis control. Here, we show that trans-autoactivation of Polo-like kinase 4 (PLK4), the trigger of centriole biogenesis, is a critical event in the spatial control of that process. We demonstrate that centrioles promote PLK4 activation through its recruitment and local accumulation. Though centriole removal reduces the proportion of active PLK4, this is rescued by concentrating PLK4 to the peroxisome lumen. Moreover, while mild overexpression of PLK4 only triggers centriole amplification at the existing centriole, higher PLK4 levels trigger both centriolar and cytoplasmatic (de novo) biogenesis. Hence, centrioles promote their assembly locally and disfavor de novo synthesis. Similar mechanisms enforcing the local concentration and/or activity of other centriole components are likely to contribute to the spatial control of centriole biogenesis under physiological conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Spatiotemporally and Mechanically Controlled Triggering of Mast Cells using Atomic Force Microscopy

    PubMed Central

    Hu, Kenneth K.; Bruce, Marc A.; Butte, Manish J.

    2014-01-01

    Mast cells are thought to be sensitive to mechanical forces, for example, coughing in asthma or pressure in “physical urticarias”. Conversion of mechanical forces to biochemical signals could potentially augment antigenic signaling. Studying the combined effects of mechanical and antigenic cues on mast cells and other hematopoietic cells has been elusive. Here, we present an approach using a modified atomic force microscope cantilever to deliver antigenic signals to mast cells while simultaneously applying mechanical forces. We developed a strategy to concurrently record degranulation events by fluorescence microscopy during antigenic triggering. Finally, we also measured the mechanical forces generated by mast cells while antigen receptors are ligated. We showed that mast cells respond to antigen delivered by the AFM cantilever with prompt degranulation and the generation of strong pushing and pulling forces. We did not discern any relationship between applied mechanical forces and the kinetics of degranulation. These experiments present a new method for dissecting the interactions of mechanical and biochemical cues in signaling responses of immune cells. PMID:24777418

  19. Pulsed laser triggered high speed microfluidic switch

    NASA Astrophysics Data System (ADS)

    Wu, Ting-Hsiang; Gao, Lanyu; Chen, Yue; Wei, Kenneth; Chiou, Pei-Yu

    2008-10-01

    We report a high-speed microfluidic switch capable of achieving a switching time of 10 μs. The switching mechanism is realized by exciting dynamic vapor bubbles with focused laser pulses in a microfluidic polydimethylsiloxane (PDMS) channel. The bubble expansion deforms the elastic PDMS channel wall and squeezes the adjacent sample channel to control its fluid and particle flows as captured by the time-resolved imaging system. A switching of polystyrene microspheres in a Y-shaped channel has also been demonstrated. This ultrafast laser triggered switching mechanism has the potential to advance the sorting speed of state-of-the-art microscale fluorescence activated cell sorting devices.

  20. Activation of context-specific attentional control sets by exogenous allocation of visual attention to the context?

    PubMed

    Gottschalk, Caroline; Fischer, Rico

    2017-03-01

    Different contexts with high versus low conflict frequencies require a specific attentional control involvement, i.e., strong attentional control for high conflict contexts and less attentional control for low conflict contexts. While it is assumed that the corresponding control set can be activated upon stimulus presentation at the respective context (e.g., upper versus lower location), the actual features that trigger control set activation are to date not described. Here, we ask whether the perceptual priming of the location context by an abrupt onset of irrelevant stimuli is sufficient in activating the context-specific attentional control set. For example, the mere onset of a stimulus might disambiguate the relevant location context and thus, serve as a low-level perceptual trigger mechanism that activates the context-specific attentional control set. In Experiment 1 and 2, the onsets of task-relevant and task-irrelevant (distracter) stimuli were manipulated at each context location to compete for triggering the activation of the appropriate control set. In Experiment 3, a prior training session enabled distracter stimuli to establish contextual control associations of their own before entering the test session. Results consistently showed that the mere onset of a task-irrelevant stimulus (with or without a context-control association) is not sufficient to activate the context-associated attentional control set by disambiguating the relevant context location. Instead, we argue that the identification of the relevant stimulus at the respective context is a precondition to trigger the activation of the context-associated attentional control set.

  1. What triggers differential DNA methylation of genes and TEs: contribution of body methylation?

    PubMed

    Inagaki, S; Kakutani, T

    2012-01-01

    Transposable elements (TEs) are epigenetically silenced with extensive DNA methylation. The silent epigenetic marks should, however, be excluded from active genes. By genetic approaches, we study mechanisms to remove the heterochromatin marks from transcribed genes. Based on our observations on control of TE transcription, we propose a possible trigger for the TE-specific accumulation of DNA methylation. A critical difference between TEs and genes could be their responses to the DNA methylation in the internal part of transcribed regions. When their internal region is methylated, genes are still transcribed, but TEs could be silenced, which may reflect the obligatory position of every critical cis-acting element within the TE itself. This initial difference of TEs and genes will be amplified by positive feedback loops to stabilize active or silent states. Thus, the mechanisms to accumulate heterochromatin marks within transcribed regions could provide a trigger to induce differential DNA methylation between genes and TEs.

  2. Do reflex seizures and spontaneous seizures form a continuum? - triggering factors and possible common mechanisms.

    PubMed

    Irmen, Friederike; Wehner, Tim; Lemieux, Louis

    2015-02-01

    Recent changes in the understanding and classification of reflex seizures have fuelled a debate on triggering mechanisms of seizures and their conceptual organization. Previous studies and patient reports have listed extrinsic and intrinsic triggers, albeit their multifactorial and dynamic nature is poorly understood. This paper aims to review literature on extrinsic and intrinsic seizure triggers and to discuss common mechanisms among them. Among self-reported seizure triggers, emotional stress is most frequently named. Reflex seizures are typically associated with extrinsic sensory triggers; however, intrinsic cognitive or proprioceptive triggers have also been assessed. The identification of a trigger underlying a seizure may be more difficult if it is intrinsic and complex, and if triggering mechanisms are multifactorial. Therefore, since observability of triggers varies and triggers are also found in non-reflex seizures, the present concept of reflex seizures may be questioned. We suggest the possibility of a conceptual continuum between reflex and spontaneous seizures rather than a dichotomy and discuss evidence to the notion that to some extent most seizures might be triggered. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  3. Remote Love Wave Triggering of Tremor in the Nankai Subduction Zone: New Observations and Dynamic Stress Modeling

    NASA Astrophysics Data System (ADS)

    Enescu, B.; Chao, K.; Obara, K.; Peng, Z.; Matsuzawa, T.; Yagi, Y.

    2013-12-01

    The triggering of deep non-volcanic tremor (NVT) in the Nankai region, southwest Japan, by the surface waves of several large teleseismic earthquakes has been well documented (e.g., Miyazawa & Mori, 2005). These previous studies report that the Nankai NVT is primarily triggered by the passage of Rayleigh waves from the teleseismic events (e.g., Miyazawa & Brodsky, 2008). The relative lack of Love wave triggering in Nankai would be, however, an exception to the general observation that triggered tremor shows a positive correlation with the triggering potential, defined using the Coulomb failure criteria (Hill, 2012). To clarify the Nankai NVT triggering mechanism, we have systematically searched for triggered tremor due to large teleseismic events (Mw ≥ 7.5) occurred from 2001 to 2012. Our present analysis focuses on western Shikoku, where triggered NVT has been previously reported (e.g., Miyazawa & Mori, 2006). From a total of 55 teleseismic events, 18 show associated triggered NVT. Our analysis presents clear evidence of triggered NVT that correlates well with the passage of Love waves. The most outstanding example is that of the 2012 M8.6 Sumatra earthquake, a strike-slip event characterized by relatively large amplitude Love waves. The incoming surface waves from this earthquake are almost strike-parallel to the Nankai subduction zone, which corresponds to a higher Love wave triggering potential (Hill, 2012). The 2001 M7.8 Kunlun, the 2003 M8.3 Tokachi-oki, the 2004 M9.2 & 2007 M8.5 Sumatra, the 2006 M8.3 Kuril-Islands and the 2008 M7.9 Wenchuan earthquakes show as well Love-wave associated NVT triggering. In most of these cases the tremor is initiated by the incoming, faster-traveling Love waves and continues during the latter, larger-amplitude Rayleigh waves. We are also conducting dynamic stress modeling to better understand the triggering mechanism of tremor. Our approach builds up on the methods of Gonzalez-Huizar & Velasco (2011) and Obara (2012). In the case of the 2012 Sumatra earthquake, we found a high correlation between the Love waves dynamic Coulomb stress change at the tremor source and the triggered NVT, for a time period of about 400s, which starts from the first Love wave cycles. Afterwards, the tremor bursts have slightly larger amplitudes and the correlation with the surface waves becomes poor. Preliminary results indicate a shallower location for these later tremors. Our results indicate that the triggering mechanism of NVT in western Shikoku is essentially the same with the one operating (e.g., Hill, 2012) in other subduction regions around the world (e.g., Cascadia). The tremor responds to excitation by both Love and Rayleigh waves according to the Coulomb failure criterion; failure, once underway, might be controlled by other mechanisms (e.g., some form of rate-state friction), which we plan to address in future studies.

  4. Method to study cell migration under uniaxial compression

    PubMed Central

    Srivastava, Nishit; Kay, Robert R.; Kabla, Alexandre J.

    2017-01-01

    The chemical, physical, and mechanical properties of the extracellular environment have a strong effect on cell migration. Aspects such as pore size or stiffness of the matrix influence the selection of the mechanism used by cells to propel themselves, including by pseudopods or blebbing. How a cell perceives its environment and how such a cue triggers a change in behavior are largely unknown, but mechanics is likely to be involved. Because mechanical conditions are often controlled by modifying the composition of the environment, separating chemical and physical contributions is difficult and requires multiple controls. Here we propose a simple method to impose a mechanical compression on individual cells without altering the composition of the matrix. Live imaging during compression provides accurate information about the cell's morphology and migratory phenotype. Using Dictyostelium as a model, we observe that a compression of the order of 500 Pa flattens the cells under gel by up to 50%. This uniaxial compression directly triggers a transition in the mode of migration from primarily pseudopodial to bleb driven in <30 s. This novel device is therefore capable of influencing cell migration in real time and offers a convenient approach with which to systematically study mechanotransduction in confined environments. PMID:28122819

  5. Internal and External Triggering Mechanism of "Smart" Nanoparticle-Based DDSs in Targeted Tumor Therapy.

    PubMed

    Qiana, Xian-Ling; Li, Jun; Wei, Ran; Lin, Hui; Xiong, Li-Xia

    2018-05-09

    Anticancer chemotherapeutics have a lot of problems via conventional drug delivery systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: "passive", "active", and "smart" targeting. To summarize the mechanisms of various internal and external "smart" stimulating factors on the basis of findings from in vivo and in vitro studies. A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), "smart" DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. In this review article, we summarize and classify the internal and external triggering mechanism of "smart" nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Tuning complement activation and pathway through controlled molecular architecture of dextran chains in nanoparticle corona.

    PubMed

    Coty, Jean-Baptiste; Eleamen Oliveira, Elquio; Vauthier, Christine

    2017-11-05

    The understanding of complement activation by nanomaterials is a key to a rational design of safe and efficient nanomedicines. This work proposed a systematic study investigating how molecular design of nanoparticle coronas made of dextran impacts on mechanisms that trigger complement activation. The nanoparticles used for this work consisted of dextran-coated poly(isobutylcyanoacrylate) (PIBCA) nanoparticles have already been thoroughly characterized. Their different capacity to trigger complement activation established on the cleavage of the protein C3 was also already described making these nanoparticles good models to investigate the relation between the molecular feature of their corona and the mechanism by which they triggered complement activation. Results of this new study show that complement activation pathways can be selected by distinct architectures formed by dextran chains composing the nanoparticle corona. Assumptions that explain the relation between complement activation mechanisms triggered by the nanoparticles and the nanoparticle corona molecular feature were proposed. These results are of interest to better understand how the design of dextran-coated nanomaterials will impact interactions with the complement system. It can open perspectives with regard to the selection of a preferential complement activation pathway or prevent the nanoparticles to activate the complement system, based on a rational choice of the corona configuration. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Forwardly-placed firearm fire control assembly

    DOEpatents

    Frickey, Steven J.

    2001-12-22

    A firearm fire control assembly for disposition in a forwardly placed support-hand operative relationship within a firearm having a combination of a firing pin and a firearm hammer adapted to engage and fire a cartridge, a sear assembly to alternately engage and disengage the combination of the firearm hammer and firing pin, and a trigger assembly including a movable trigger mechanism that is operable to engage the sear assembly to cause the firearm hammer firing pin combination to fire the firearm, a fire control assembly including a fire control depression member and a fire control rod operably connected to the depression member, and being positioned in a forward disposition disposed within a forestock of the firearm, and the depression member adapted to be operably engaged and depressed by the user's conventional forwardly placed support hand to maneuver the fire control rod to provide firing control of the firing of the firearm.

  8. Indocyanine Green-Loaded Liposomes for Light-Triggered Drug Release.

    PubMed

    Lajunen, Tatu; Kontturi, Leena-Stiina; Viitala, Lauri; Manna, Moutusi; Cramariuc, Oana; Róg, Tomasz; Bunker, Alex; Laaksonen, Timo; Viitala, Tapani; Murtomäki, Lasse; Urtti, Arto

    2016-06-06

    Light-triggered drug delivery systems enable site-specific and time-controlled drug release. In previous work, we have achieved this with liposomes containing gold nanoparticles in the aqueous core. Gold nanoparticles absorb near-infrared light and release the energy as heat that increases the permeability of the liposomal bilayer, thus releasing the contents of the liposome. In this work, we replaced the gold nanoparticles with the clinically approved imaging agent indocyanine green (ICG). The ICG liposomes were stable at storage conditions (4-22 °C) and at body temperature, and fast near-infrared (IR) light-triggered drug release was achieved with optimized phospholipid composition and a 1:50 ICG-to-lipid molar ratio. Encapsulated small molecular calcein and FITC-dextran (up to 20 kDa) were completely released from the liposomes after light exposure for 15 s. Location of ICG in the PEG layer of the liposomes was simulated with molecular dynamics. ICG has important benefits as a light-triggering agent in liposomes: fast content release, improved stability, improved possibility of liposomal size control, regulatory approval to use in humans, and the possibility of imaging the in vivo location of the liposomes based on the fluorescence of ICG. Near-infrared light used as a triggering mechanism has good tissue penetration and safety. Thus, ICG liposomes are an attractive option for light-controlled and efficient delivery of small and large drug molecules.

  9. Antiviral immune responses: triggers of or triggered by autoimmunity?

    PubMed Central

    Münz, Christian; Lünemann, Jan D.; Getts, Meghann Teague; Miller, Stephen D.

    2010-01-01

    Several common autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus (SLE) and multiple sclerosis, are genetically linked to distinct human MHC class II molecules and other immune modulators. However, genetic predisposition is only one risk factor for the development of these diseases, and low concordance rates in monozygotic twins as well as geographical distribution of disease risk point towards environmental factors in the genesis of these diseases. Among these environmental factors, infections have been implicated in the onset and/or promotion of autoimmunity. In this review, we outline mechanisms by which pathogens can trigger autoimmune disease, and also pathways by which infection and immune control of infectious disease might be dysregulated during autoimmunity. PMID:19319143

  10. Timing paradox of stepping and falls in ageing: not so quick and quick(er) on the trigger

    PubMed Central

    Mille, Marie‐Laure

    2016-01-01

    Abstract Physiological and degenerative changes affecting human standing balance are major contributors to falls with ageing. During imbalance, stepping is a powerful protective action for preserving balance that may be voluntarily initiated in recognition of a balance threat, or be induced by an externally imposed mechanical or sensory perturbation. Paradoxically, with ageing and falls, initiation slowing of voluntary stepping is observed together with perturbation‐induced steps that are triggered as fast as or faster than for younger adults. While age‐associated changes in sensorimotor conduction, central neuronal processing and cognitive functions are linked to delayed voluntary stepping, alterations in the coupling of posture and locomotion may also prolong step triggering. It is less clear, however, how these factors may explain the accelerated triggering of induced stepping. We present a conceptual model that addresses this issue. For voluntary stepping, a disruption in the normal coupling between posture and locomotion may underlie step‐triggering delays through suppression of the locomotion network based on an estimation of the evolving mechanical state conditions for stability. During induced stepping, accelerated step initiation may represent an event‐triggering process whereby stepping is released according to the occurrence of a perturbation rather than to the specific sensorimotor information reflecting the evolving instability. In this case, errors in the parametric control of induced stepping and its effectiveness in stabilizing balance would be likely to occur. We further suggest that there is a residual adaptive capacity with ageing that could be exploited to improve paradoxical triggering and other changes in protective stepping to impact fall risk. PMID:26915664

  11. Influence of Grain Size on Mechanical Responses in Beta Ti-12Mo Alloy Demonstrating Concurrent Twinning-Induced Plasticity/Transformation-induced Plasticity Effects

    NASA Astrophysics Data System (ADS)

    Zhang, D. C.; Xue, Q.; Lei, J. F.; Ma, Y. J.; Yang, R.; Wang, C.

    2018-06-01

    Metastable β Ti-12Mo wt pct alloys with controllable grain sizes are successfully produced, and the effect of grain size on mechanical responses has been thoroughly investigated. It is found that target alloys possess concurrent twinning-induced plasticity (TWIP) and transformation-induced plasticity (TRIP) features. Mechanisms governing mechanical properties through well-manipulated tensile experiments, detailed microstructure analysis, as well as strong correlations between triggering stress and twinning/phase transformation are offered.

  12. Silver nanoparticle aggregation not triggered by an ionic strength mechanism

    NASA Astrophysics Data System (ADS)

    Botasini, Santiago; Méndez, Eduardo

    2013-04-01

    The synthesis of stable colloidal solutions of silver nanoparticles is a major goal in the industry to control their fate in aqueous solutions. The present work studies 10-20-nm silver nanoparticle aggregation triggered by the presence of chloride ions. The aggregation process was followed by UV-Vis-NIR spectroscopy and transmission electron microscopy. We found that the mechanism involved differs from the classic explanation of nanoparticle aggregation triggered by an increase in the ionic strength. Moreover, our results give evidence that even when nanoparticles are resistant to an increment of the total amount of ions, the formation of insoluble salts in the vicinity of the nanoparticle is enough to induce the aggregation. The presence of silver chloride around the silver nanoparticles was documented by an X-ray diffraction pattern and electrochemical methods because chloride anions are ubiquitous in real media; this alternative process jeopardized the development of many applications with silver nanoparticles that depend on the use of stable colloids.

  13. Clastic pipe characteristics and distributions throughout the Colorado Plateau: Implications for paleoenvironment and paleoseismic controls

    NASA Astrophysics Data System (ADS)

    Wheatley, D. F.; Chan, M. A.; Sprinkel, D. A.

    2016-10-01

    Clastic pipes occur throughout much of the Phanerozoic strata of the Colorado Plateau and provide a unique opportunity to test the validly of various deformation and triggering mechanism hypotheses in the context of their tectono-stratigraphic and paleoenvironmental settings. Pipes dominantly occur in Jurassic strata and preferentially in eolian (especially interdune), sabkha, and fluvial deposits because these sediments contained interbedded fine-grained and water-saturated, high-porosity, coarse-grained facies. The greatest geographic concentrations of pipes occur in three trends: (1) a northeast trend from the Lake Powell to Moab areas of southern and southeastern Utah, (2) an east-west trend in northern Arizona within and north of the Grand Canyon, and (3) a west-northwest-east-southeast trend along Interstate 40 west of Albuquerque, New Mexico. Many pipes formed due to liquefaction and fluidization and were potentially triggered by seismic activity originating from basement-cored uplifts within the Colorado Plateau, although other trigger mechanisms cannot be completely eliminated. Some breccia pipes within northern Arizona that are rooted in karst are the exception to this interpretation. Pipes possess unique depositional and triggering requirements and thus provide an excellent opportunity to understand the interplay of sedimentology and tectonics within continental systems.

  14. The Effects of Triggering Mechanisms on the Energy Absorption Capability of Circular Jute/Epoxy Composite Tubes under Quasi-Static Axial Loading

    NASA Astrophysics Data System (ADS)

    Sivagurunathan, Rubentheran; Lau Tze Way, Saijod; Sivagurunathan, Linkesvaran; Yaakob, Mohd. Yuhazri

    2018-01-01

    The usage of composite materials have been improving over the years due to its superior mechanical properties such as high tensile strength, high energy absorption capability, and corrosion resistance. In this present study, the energy absorption capability of circular jute/epoxy composite tubes were tested and evaluated. To induce the progressive crushing of the composite tubes, four different types of triggering mechanisms were used which were the non-trigger, single chamfered trigger, double chamfered trigger and tulip trigger. Quasi-static axial loading test was carried out to understand the deformation patterns and the load-displacement characteristics for each composite tube. Besides that, the influence of energy absorption, crush force efficiency, peak load, mean load and load-displacement history were examined and discussed. The primary results displayed a significant influence on the energy absorption capability provided that stable progressive crushing occurred mostly in the triggered tubes compared to the non-triggered tubes. Overall, the tulip trigger configuration attributed the highest energy absorption.

  15. Synaptic vesicle recycling: steps and principles.

    PubMed

    Rizzoli, Silvio O

    2014-04-16

    Synaptic vesicle recycling is one of the best-studied cellular pathways. Many of the proteins involved are known, and their interactions are becoming increasingly clear. However, as for many other pathways, it is still difficult to understand synaptic vesicle recycling as a whole. While it is generally possible to point out how synaptic reactions take place, it is not always easy to understand what triggers or controls them. Also, it is often difficult to understand how the availability of the reaction partners is controlled: how the reaction partners manage to find each other in the right place, at the right time. I present here an overview of synaptic vesicle recycling, discussing the mechanisms that trigger different reactions, and those that ensure the availability of reaction partners. A central argument is that synaptic vesicles bind soluble cofactor proteins, with low affinity, and thus control their availability in the synapse, forming a buffer for cofactor proteins. The availability of cofactor proteins, in turn, regulates the different synaptic reactions. Similar mechanisms, in which one of the reaction partners buffers another, may apply to many other processes, from the biogenesis to the degradation of the synaptic vesicle.

  16. How do you approach seizures in the high altitude traveler?

    PubMed

    Maa, Edward H

    2011-01-01

    Counseling patients who suffer first-time or break- through seizures can be difficult, particularly when controllable external factors may be contributing to the lowering of their seizure threshold. High altitude as a potential trigger for seizures is a common question in our epilepsy clinics in Colorado, and this article reviews the existing anecdotal literature, presents our local experience with high altitude seizures (HAS), offers possible mechanisms to explain how high altitude may trigger seizures, and suggests an initial work-up and prophylactic strategies for future high altitude exposures.

  17. Development of Overflow-Prevention Valve with Trigger Mechanism.

    NASA Astrophysics Data System (ADS)

    Ishino, Yuji; Mizuno, Takeshi; Takasaki, Masaya

    2016-09-01

    A new overflow-prevention valve for combustible fluid is developed which uses a trigger mechanism. Loading arms for combustible fluid are used for transferring oil from a tanker to tanks and vice versa. The loading arm has a valve for preventing overflow. Overflow- prevention valves cannot use any electric component to avoid combustion. Therefore, the valve must be constructed only by mechanical parts. The conventional overflow-prevention valve uses fluid and pneumatic forces. It consists of a sensor probe, a cylinder, a main valve for shutting off the fluid and a locking mechanism for holding an open state of the main valve. The proposed overflow-prevention valve uses the pressure due to the height difference between the fluid level of the tank and the sensor probe. However, the force of the cylinder produced by the pressure is too small to release the locking mechanism. Therefore, a trigger mechanism is introduced between the cylinder and the locking mechanism. The trigger mechanism produces sufficient force to release the locking mechanism and close the main valve when the height of fluid exceeds a threshold value. A trigger mechanism is designed and fabricated. The operation necessary for closing the main valve is conformed experimentally.

  18. Kinematic evaluation of the finger's interphalangeal joints coupling mechanism--variability, flexion-extension differences, triggers, locking swanneck deformities, anthropometric correlations.

    PubMed

    Leijnse, J N A L; Quesada, P M; Spoor, C W

    2010-08-26

    The human finger contains tendon/ligament mechanisms essential for proper control. One mechanism couples the movements of the interphalangeal joints when the (unloaded) finger is flexed with active deep flexor. This study's aim was to accurately determine in a large finger sample the kinematics and variability of the coupled interphalangeal joint motions, for potential clinical and finger model validation applications. The data could also be applied to humanoid robotic hands. Sixty-eight fingers were measured in seventeen hands in nine subjects. Fingers exhibited great joint mobility variability, with passive proximal interphalangeal hyperextension ranging from zero to almost fifty degrees. Increased measurement accuracy was obtained by using marker frames to amplify finger segment motions. Gravitational forces on the marker frames were not found to invalidate measurements. The recorded interphalangeal joint trajectories were highly consistent, demonstrating the underlying coupling mechanism. The increased accuracy and large sample size allowed for evaluation of detailed trajectory variability, systematic differences between flexion and extension trajectories, and three trigger types, distinct from flexor tendon triggers, involving initial flexion deficits in either proximal or distal interphalangeal joint. The experimental methods, data and analysis should advance insight into normal and pathological finger biomechanics (e.g., swanneck deformities), and could help improve clinical differential diagnostics of trigger finger causes. The marker frame measuring method may be useful to quantify interphalangeal joints trajectories in surgical/rehabilitative outcome studies. The data as a whole provide the most comprehensive collection of interphalangeal joint trajectories for clinical reference and model validation known to us to date. 2010 Elsevier Ltd. All rights reserved.

  19. Hydrogen peroxide mechanosynthesis in siloxane-hydrogel contact lenses.

    PubMed

    Tavazzi, Silvia; Ferraro, Lorenzo; Cozza, Federica; Pastori, Valentina; Lecchi, Marzia; Farris, Stefano; Borghesi, Alessandro

    2014-11-26

    Drug-loaded contact lenses are emerging as the preferred treatment method for several ocular diseases, and efforts are being directed to promote extended and controlled delivery. One strategy is based on delivery induced by environmental triggers. One of these triggers can be hydrogen peroxide, since many platforms based on drug-loaded nanoparticles were demonstrated to be hydrogen-peroxide responsive. This is particularly interesting when hydrogen peroxide is the result of a specific pathophysiological condition. Otherwise, an alternative route to induce drug delivery is here proposed, namely the mechano-synthesis. The present work represents the proof-of-concept of the mechanosynthesis of hydrogen peroxide in siloxane-hydrogel contact lenses as a consequence of the cleavage of siloxane bonds at the interface between the polymer and water in aqueous phase. Their spongy morphology makes contact lenses promising systems for mechanical-to-chemical energy conversion, since the amount of hydrogen peroxide is expected to scale with the interfacial area between the polymer and water. The eyelid pressure during wear is sufficient to induce the hydrogen peroxide synthesis with concentrations which are biocompatible and suitable to trigger the drug release through hydrogen-peroxide-responsive platforms. For possible delivery on demand, the integration of piezoelectric polymers in the siloxane-hydrogel contact lenses could be designed, whose mechanical deformation could be induced by an applied wireless-controlled voltage.

  20. Aftershocks driven by afterslip and fluid pressure sweeping through a fault-fracture mesh

    USGS Publications Warehouse

    Ross, Zachary E.; Rollins, Christopher; Cochran, Elizabeth S.; Hauksson, Egill; Avouac, Jean-Philippe; Ben-Zion, Yehuda

    2017-01-01

    A variety of physical mechanisms are thought to be responsible for the triggering and spatiotemporal evolution of aftershocks. Here we analyze a vigorous aftershock sequence and postseismic geodetic strain that occurred in the Yuha Desert following the 2010 Mw 7.2 El Mayor-Cucapah earthquake. About 155,000 detected aftershocks occurred in a network of orthogonal faults and exhibit features of two distinct mechanisms for aftershock triggering. The earliest aftershocks were likely driven by afterslip that spread away from the main shock with the logarithm of time. A later pulse of aftershocks swept again across the Yuha Desert with square root time dependence and swarm-like behavior; together with local geological evidence for hydrothermalism, these features suggest that the events were driven by fluid diffusion. The observations illustrate how multiple driving mechanisms and the underlying fault structure jointly control the evolution of an aftershock sequence.

  1. Integration of the Super Nova early warning system with the NOvA Trigger

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

    Habig, Alec; Zirnstein, Jan

    The NOvA experiment, with a baseline of 810km, samples Fermilab’s upgraded NuMI beam with a Near Detector on-site and a Far Detector (FD) at Ash River, MN, to observe oscillations of muon neutrinos. The 344,064 liquid scintillator-filled cells of the 14 kton FD provide high granularity of a large detector mass and enable us to also study non-accelerator based neutrinos with our Data Driven Trigger framework. This paper will focus on the real time integration of the SNEWS with the NOvA Trigger where we have set up an XML-RPC based messaging system to inject the SNEWS signal directly into ourmore » trigger. In conclusion, this presents a departure from the E-Mail based notification mechanism used by SNEWS in the past and allows NOvA more control over propagation and transmission timing.« less

  2. Integration of the Super Nova early warning system with the NOvA Trigger

    DOE PAGES

    Habig, Alec; Zirnstein, Jan

    2015-12-23

    The NOvA experiment, with a baseline of 810km, samples Fermilab’s upgraded NuMI beam with a Near Detector on-site and a Far Detector (FD) at Ash River, MN, to observe oscillations of muon neutrinos. The 344,064 liquid scintillator-filled cells of the 14 kton FD provide high granularity of a large detector mass and enable us to also study non-accelerator based neutrinos with our Data Driven Trigger framework. This paper will focus on the real time integration of the SNEWS with the NOvA Trigger where we have set up an XML-RPC based messaging system to inject the SNEWS signal directly into ourmore » trigger. In conclusion, this presents a departure from the E-Mail based notification mechanism used by SNEWS in the past and allows NOvA more control over propagation and transmission timing.« less

  3. Development and Applications of Photo-triggered Theranostic Agents

    PubMed Central

    Rai, Prakash; Mallidi, Srivallesha; Zheng, Xiang; Rahmanzadeh, Ramtin; Mir, Youssef; Elrington, Stefan; Khurshid, Ahmat; Hasan, Tayyaba

    2010-01-01

    Theranostics, the fusion of therapy and diagnostics for optimizing efficacy and safety of therapeutic regimes, is a growing field that is paving the way towards the goal of personalized medicine for the benefit of patients. The use of light as a remote-activation mechanism for drug delivery has received increased attention due to its advantages in highly specific spatial and temporal control of compound release. Photo-triggered theranostic constructs could facilitate an entirely new category of clinical solutions which permit early recognition of the disease by enhancing contrast in various imaging modalities followed by the tailored guidance of therapy. Finally, such theranostic agents could aid imaging modalities in monitoring response to therapy. This article reviews recent developments in the use of light-triggered theranostic agents for simultaneous imaging and photoactivation of therapeutic agents. Specifically, we discuss recent developments in the use of theranostic agents for photodynamic-, photothermal- or photo-triggered chemo-therapy for several diseases. PMID:20858520

  4. Detonation control

    DOEpatents

    Mace, Jonathan L.; Seitz, Gerald J.; Bronisz, Lawrence E.

    2016-10-25

    Detonation control modules and detonation control circuits are provided herein. A trigger input signal can cause a detonation control module to trigger a detonator. A detonation control module can include a timing circuit, a light-producing diode such as a laser diode, an optically triggered diode, and a high-voltage capacitor. The trigger input signal can activate the timing circuit. The timing circuit can control activation of the light-producing diode. Activation of the light-producing diode illuminates and activates the optically triggered diode. The optically triggered diode can be coupled between the high-voltage capacitor and the detonator. Activation of the optically triggered diode causes a power pulse to be released from the high-voltage capacitor that triggers the detonator.

  5. System and method of active vibration control for an electro-mechanically cooled device

    DOEpatents

    Lavietes, Anthony D.; Mauger, Joseph; Anderson, Eric H.

    2000-01-01

    A system and method of active vibration control of an electro-mechanically cooled device is disclosed. A cryogenic cooling system is located within an environment. The cooling system is characterized by a vibration transfer function, which requires vibration transfer function coefficients. A vibration controller generates the vibration transfer function coefficients in response to various triggering events. The environments may differ by mounting apparatus, by proximity to vibration generating devices, or by temperature. The triggering event may be powering on the cooling system, reaching an operating temperature, or a reset action. A counterbalance responds to a drive signal generated by the vibration controller, based on the vibration signal and the vibration transfer function, which adjusts vibrations. The method first places a cryogenic cooling system within a first environment and then generates a first set of vibration transfer function coefficients, for a vibration transfer function of the cooling system. Next, the cryogenic cooling system is placed within a second environment and a second set of vibration transfer function coefficients are generated. Then, a counterbalance is driven, based on the vibration transfer function, to reduce vibrations received by a vibration sensitive element.

  6. More pain, more gain: Blocking the opioid system boosts adaptive cognitive control.

    PubMed

    van Steenbergen, Henk; Weissman, Daniel H; Stein, Dan J; Malcolm-Smith, Susan; van Honk, Jack

    2017-06-01

    The ability to adaptively increase cognitive control in response to cognitive challenges is crucial for goal-directed behavior. Recent findings suggest that aversive arousal triggers adaptive increases of control, but the neurochemical mechanisms underlying these effects remain unclear. Given the known contributions of the opioid system to hedonic states, we investigated whether blocking this system increases adaptive control modulations. To do so, we conducted a double-blind, placebo-controlled psychopharmacological study (n=52 females) involving a Stroop-like task. Specifically, we assessed the effect of naltrexone, an opioid blocker most selective to the mu-opioid system, on two measures of adaptive control that are thought to depend differentially on aversive arousal: post-error slowing and conflict adaptation. Consistent with our hypothesis, relative to placebo, naltrexone increased post-error slowing without influencing conflict adaptation. This finding not only supports the view that aversive arousal triggers adaptive control but also reveals a novel role for the opioid system in modulating such effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Molecular mechanisms mediating immune priming in Anopheles gambiae mosquitos

    USDA-ARS?s Scientific Manuscript database

    The Anopheles gambiae immune priming response is triggered when Plasmodium ookinetes invade the mosquito midgut and the microbiota comes in direct contact with injured cells. This is a long-lasting response that confers the challenged mosquito enhanced ability to control subsequent Plasmodium infect...

  8. Timing paradox of stepping and falls in ageing: not so quick and quick(er) on the trigger.

    PubMed

    Rogers, Mark W; Mille, Marie-Laure

    2016-08-15

    Physiological and degenerative changes affecting human standing balance are major contributors to falls with ageing. During imbalance, stepping is a powerful protective action for preserving balance that may be voluntarily initiated in recognition of a balance threat, or be induced by an externally imposed mechanical or sensory perturbation. Paradoxically, with ageing and falls, initiation slowing of voluntary stepping is observed together with perturbation-induced steps that are triggered as fast as or faster than for younger adults. While age-associated changes in sensorimotor conduction, central neuronal processing and cognitive functions are linked to delayed voluntary stepping, alterations in the coupling of posture and locomotion may also prolong step triggering. It is less clear, however, how these factors may explain the accelerated triggering of induced stepping. We present a conceptual model that addresses this issue. For voluntary stepping, a disruption in the normal coupling between posture and locomotion may underlie step-triggering delays through suppression of the locomotion network based on an estimation of the evolving mechanical state conditions for stability. During induced stepping, accelerated step initiation may represent an event-triggering process whereby stepping is released according to the occurrence of a perturbation rather than to the specific sensorimotor information reflecting the evolving instability. In this case, errors in the parametric control of induced stepping and its effectiveness in stabilizing balance would be likely to occur. We further suggest that there is a residual adaptive capacity with ageing that could be exploited to improve paradoxical triggering and other changes in protective stepping to impact fall risk. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  9. Controlled Sol-Gel Transitions of a Thermoresponsive Polymer in a Photoswitchable Azobenzene Ionic Liquid as a Molecular Trigger.

    PubMed

    Wang, Caihong; Hashimoto, Kei; Tamate, Ryota; Kokubo, Hisashi; Watanabe, Masayoshi

    2018-01-02

    Producing ionic liquids (ILs) that function as molecular trigger for macroscopic change is a challenging issue. Photoisomerization of an azobenzene IL at the molecular level evokes a macroscopic response (light-controlled mechanical sol-gel transitions) for ABA triblock copolymer solutions. The A endblocks, poly(2-phenylethyl methacrylate), show a lower critical solution temperature in the IL mixture containing azobenzene, while the B midblock, poly(methyl methacrylate), is compatible with the mixture. In a concentrated polymer solution, different gelation temperatures were observed in it under dark and UV conditions. Light-controlled sol-gel transitions were achieved by a photoresponsive solubility change of the A endblocks upon photoisomerization of the azobenzene IL. Therefore, an azobenzene IL as a molecular switch can tune the self-assembly of a thermoresponsive polymer, leading to macroscopic light-controlled sol-gel transitions. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Triggered instabilities in rocket motors and active combustion control for an incinerator afterburner

    NASA Astrophysics Data System (ADS)

    Wicker, Josef M.

    1999-11-01

    Two branches of research are conducted in this thesis. The first deals with nonlinear combustion response as a mechanism for triggering combustion instabilities in solid rocket motors. A nonlinear wave equation is developed to study a wide class of combustion response functions to second-order in fluctuation amplitude. Conditions for triggering are derived from analysis of limit cycles, and regions of triggering are found in parametric space. Introduction of linear cross-coupling and quadratic self-coupling among the acoustic modes appears to be how the nonlinear combustion response produces triggering to a stable limit cycle. Regions of initial conditions corresponding to stable pulses were found, suggesting that stability depends on initial phase angle and harmonic content, as well as the composite amplitude, of the pulse. Also, dependence of nonlinear stability upon system parameters is considered. The second part of this thesis presents research for a controller to improve the emissions of an incinerator afterburner. The developed controller was experimentally tested at the Naval Air Warfare Center (NAWC), on a 50kW-scale model of an afterburner for Naval shipboard incinerator applications. Acoustic forcing of the combustor's reacting shear layer is used to control the formation of coherent vortical structures, within which favorable fuel-air mixing and efficient combustion can occur. Laser-based measurements of CO emissions are used as the performance indicator for the combustor. The controller algorithm is based on the downhill simplex method and adjusts the shear layer forcing parameters in order to minimize the CO emissions. The downhill simplex method was analyzed with respect to its behavior in the face of time-variation of the plant and noise in the sensor signal, and was modified to account for these difficulties. The control system has experimentally demonstrated the ability (1) to find optimal control action for single- and multi-variable control, (2) to maintain optimal control for time-varying operating states, and (3) to automatically adjust auxiliary fuel in response to changing stoichiometry of the incoming waste pyrolysis gas. Also presented but not tested in the experiments are an expert-type model-guidance feature to aid convergence of the controller to optimum control, and methodology for maintaining flammability.

  11. Is cognitive control automatic? New insights from transcranial magnetic stimulation.

    PubMed

    Cona, G; Treccani, B; Umiltà, C A

    2016-10-01

    Cognitive control has been classically considered as a flexible process engaged to pursue intentional behaviors, as distinct from automatic processes, which are unintentional, inflexible, and triggered by unconscious mechanisms. Our study challenged this view, showing that such a distinction may not be so clear-cut. We analyzed motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation to investigate the neurocognitive mechanisms occurring in a conflict task during trials that either required or did not require a response. We observed a Simon effect on MEPs and sequential modulations of such effects on both kinds of trials. Sequential modulations are usually explained as resulting from the engagement of intentional control mechanisms. Our findings rule against this idea, suggesting that these effects are the result of a mechanism that detects and resolves conflict even when there is no intention to select any response. Accordingly, cognitive control also seems to operate without intention, acting in an automatic fashion.

  12. Electromechanical actuator for the tongs of a servomanipulator

    DOEpatents

    Martin, H. Lee; Killough, Stephen M.

    1986-01-01

    Computer-augmented electromechanical system is provided for controlling the tongs of a servomanipulator. The mechanical tongs are motor-driven through the remote slave arm of the manipulator, and the motor control current is supplied by a position sensor which senses the position of a spring-loaded trigger in the master arm handle on the manipulator. The actuator for the tongs provides the operator with artificial force reflection in a unilateral force-force control loop.

  13. Firmware Development Improves System Efficiency

    NASA Technical Reports Server (NTRS)

    Chern, E. James; Butler, David W.

    1993-01-01

    Most manufacturing processes require physical pointwise positioning of the components or tools from one location to another. Typical mechanical systems utilize either stop-and-go or fixed feed-rate procession to accomplish the task. The first approach achieves positional accuracy but prolongs overall time and increases wear on the mechanical system. The second approach sustains the throughput but compromises positional accuracy. A computer firmware approach has been developed to optimize this point wise mechanism by utilizing programmable interrupt controls to synchronize engineering processes 'on the fly'. This principle has been implemented in an eddy current imaging system to demonstrate the improvement. Software programs were developed that enable a mechanical controller card to transmit interrupts to a system controller as a trigger signal to initiate an eddy current data acquisition routine. The advantages are: (1) optimized manufacturing processes, (2) increased throughput of the system, (3) improved positional accuracy, and (4) reduced wear and tear on the mechanical system.

  14. Neuro Emotional Technique for the treatment of trigger point sensitivity in chronic neck pain sufferers: A controlled clinical trial

    PubMed Central

    Bablis, Peter; Pollard, Henry; Bonello, Rod

    2008-01-01

    Background Trigger points have been shown to be active in many myofascial pain syndromes. Treatment of trigger point pain and dysfunction may be explained through the mechanisms of central and peripheral paradigms. This study aimed to investigate whether the mind/body treatment of Neuro Emotional Technique (NET) could significantly relieve pain sensitivity of trigger points presenting in a cohort of chronic neck pain sufferers. Methods Sixty participants presenting to a private chiropractic clinic with chronic cervical pain as their primary complaint were sequentially allocated into treatment and control groups. Participants in the treatment group received a short course of Neuro Emotional Technique that consists of muscle testing, general semantics and Traditional Chinese Medicine. The control group received a sham NET protocol. Outcome measurements included pain assessment utilizing a visual analog scale and a pressure gauge algometer. Pain sensitivity was measured at four trigger point locations: suboccipital region (S); levator scapulae region (LS); sternocleidomastoid region (SCM) and temporomandibular region (TMJ). For each outcome measurement and each trigger point, we calculated the change in measurement between pre- and post- treatment. We then examined the relationships between these measurement changes and six independent variables (i.e. treatment group and the above five additional participant variables) using forward stepwise General Linear Model. Results The visual analog scale (0 to 10) had an improvement of 7.6 at S, 7.2 at LS, 7.5 at SCM and 7.1 at the TMJ in the treatment group compared with no improvement of at S, and an improvement of 0.04 at LS, 0.1 at SCM and 0.1 at the TMJ point in the control group, (P < 0.001). Conclusion After a short course of NET treatment, measurements of visual analog scale and pressure algometer recordings of four trigger point locations in a cohort of chronic neck pain sufferers were significantly improved when compared to a control group which received a sham protocol of NET. Chronic neck pain sufferers may benefit from NET treatment in the relief of trigger point sensitivity. Further research including long-term randomised controlled trials for the effect of NET on chronic neck pain, and other chronic pain syndromes are recommended. Trial Registration This trial has been registered and allocated the Australian Clinical Trials Registry (ACTR) number ACTRN012607000358448. The ACTR has met the requirements of the ICMJE's trials registration policy and is an ICMJE acceptable registry. PMID:18495042

  15. Networked event-triggered control: an introduction and research trends

    NASA Astrophysics Data System (ADS)

    Mahmoud, Magdi S.; Sabih, Muhammad

    2014-11-01

    A physical system can be studied as either continuous time or discrete-time system depending upon the control objectives. Discrete-time control systems can be further classified into two categories based on the sampling: (1) time-triggered control systems and (2) event-triggered control systems. Time-triggered systems sample states and calculate controls at every sampling instant in a periodic fashion, even in cases when states and calculated control do not change much. This indicates unnecessary and useless data transmission and computation efforts of a time-triggered system, thus inefficiency. For networked systems, the transmission of measurement and control signals, thus, cause unnecessary network traffic. Event-triggered systems, on the other hand, have potential to reduce the communication burden in addition to reducing the computation of control signals. This paper provides an up-to-date survey on the event-triggered methods for control systems and highlights the potential research directions.

  16. Cdk1 Activates Pre-mitotic Nuclear Envelope Dynein Recruitment and Apical Nuclear Migration in Neural Stem Cells.

    PubMed

    Baffet, Alexandre D; Hu, Daniel J; Vallee, Richard B

    2015-06-22

    Dynein recruitment to the nuclear envelope is required for pre-mitotic nucleus-centrosome interactions in nonneuronal cells and for apical nuclear migration in neural stem cells. In each case, dynein is recruited to the nuclear envelope (NE) specifically during G2 via two nuclear pore-mediated mechanisms involving RanBP2-BicD2 and Nup133-CENP-F. The mechanisms responsible for cell-cycle control of this behavior are unknown. We now find that Cdk1 serves as a direct master controller for NE dynein recruitment in neural stem cells and HeLa cells. Cdk1 phosphorylates conserved sites within RanBP2 and activates BicD2 binding and early dynein recruitment. Late recruitment is triggered by a Cdk1-induced export of CENP-F from the nucleus. Forced NE targeting of BicD2 overrides Cdk1 inhibition, fully rescuing dynein recruitment and nuclear migration in neural stem cells. These results reveal how NE dynein recruitment is cell-cycle regulated and identify the trigger mechanism for apical nuclear migration in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Geologic fracturing method and resulting fractured geologic structure

    DOEpatents

    Mace, Jonathan L.; Bradley, Christopher R.; Greening, Doran R.; Steedman, David W.

    2016-11-08

    Detonation control modules and detonation control circuits are provided herein. A trigger input signal can cause a detonation control module to trigger a detonator. A detonation control module can include a timing circuit, a light-producing diode such as a laser diode, an optically triggered diode, and a high-voltage capacitor. The trigger input signal can activate the timing circuit. The timing circuit can control activation of the light-producing diode. Activation of the light-producing diode illuminates and activates the optically triggered diode. The optically triggered diode can be coupled between the high-voltage capacitor and the detonator. Activation of the optically triggered diode causes a power pulse to be released from the high-voltage capacitor that triggers the detonator.

  18. Study on Excitation-triggered Damage Mechanism in Perilous Rock

    NASA Astrophysics Data System (ADS)

    Chen, Hongkai; Wang, Shengjuan

    2017-12-01

    Chain collapse is easy to happen for perilous rock aggregate locating on steep high slope, and one of the key scientific problems is the damage mechanism of perilous rock under excitation action at perilous rock rupture. This paper studies excitation-triggered damage mechanism in perilous rock by wave mechanics, which gives three conclusions. Firstly, when only the normal incidence attenuation spread of excitation wave is considered, while the energy loss is ignored for excitation wave to spread in perilous rock aggregate, the paper establishes one method to calculate peak velocity when excitation wave passes through boundary between any two perilous rock blocks in perilous rock aggregate. Secondly, following by Sweden and Canmet criteria, the paper provides one wave velocity criterion for excitation-triggered damage in the aggregate. Thirdly, assuming double parameters of volume strain of cracks or fissures in rock meet the Weibull distribution, one method to estimate micro-fissure in excitation-triggered damage zone in perilous rock aggregate is established. The studies solve the mechanical description problem for excitation-triggered damage in perilous rock, which is valuable in studies on profoundly rupture mechanism.

  19. Polymeric micelles with stimuli-triggering systems for advanced cancer drug targeting.

    PubMed

    Nakayama, Masamichi; Akimoto, Jun; Okano, Teruo

    2014-08-01

    Since the 1990s, nanoscale drug carriers have played a pivotal role in cancer chemotherapy, acting through passive drug delivery mechanisms and subsequent pharmaceutical action at tumor tissues with reduction of adverse effects. Polymeric micelles, as supramolecular assemblies of amphiphilic polymers, have been considerably developed as promising drug carrier candidates, and a number of clinical studies of anticancer drug-loaded polymeric micelle carriers for cancer chemotherapy applications are now in progress. However, these systems still face several issues; at present, the simultaneous control of target-selective delivery and release of incorporated drugs remains difficult. To resolve these points, the introduction of stimuli-responsive mechanisms to drug carrier systems is believed to be a promising approach to provide better solutions for future tumor drug targeting strategies. As possible trigger signals, biological acidic pH, light, heating/cooling and ultrasound actively play significant roles in signal-triggering drug release and carrier interaction with target cells. This review article summarizes several molecular designs for stimuli-responsive polymeric micelles in response to variation of pH, light and temperature and discusses their potentials as next-generation tumor drug targeting systems.

  20. Activity-induced convergence of APP and BACE-1 in acidic microdomains via an endocytosis-dependent pathway

    PubMed Central

    Das, Utpal; Scott, David; Ganguly, Archan; Koo, Edward H.; Tang, Yong; Roy, Subhojit

    2013-01-01

    The convergence of APP (substrate) and BACE-1 (enzyme) is a rate-limiting, obligatory event triggering the amyloidogenic pathway – a key step in Alzheimer’s disease (AD) pathology. However, as both APP/BACE-1 are highly expressed in brain, mechanisms precluding their unabated convergence are unclear. Exploring dynamic localization of APP/BACE-1 in cultured hippocampal neurons, we found that after synthesis via the secretory-pathway, dendritic APP/BACE-1-containing vesicles are largely segregated in physiologic states. While BACE-1 is largely sorted into acidic recycling endosomes, APP is conveyed in Golgi-derived vesicles. However upon activity-induction – a known trigger of the amyloidogenic pathway – APP is routed into BACE-1-positive recycling endosomes via a clathrin-dependent mechanism. A partitioning/convergence of APP/BACE-1 vesicles is also apparent in control/AD brains respectively. Considering BACE-1 is optimally active in an acidic environment, our experiments suggest that neurons have evolved trafficking strategies that normally limit APP/BACE-1 proximity; and also uncover a pathway routing APP into BACE-1-containing organelles – triggering amyloidogenesis. PMID:23931995

  1. Remote modulation of neural activities via near-infrared triggered release of biomolecules.

    PubMed

    Li, Wei; Luo, Rongcong; Lin, Xudong; Jadhav, Amol D; Zhang, Zicong; Yan, Li; Chan, Chung-Yuan; Chen, Xianfeng; He, Jufang; Chen, Chia-Hung; Shi, Peng

    2015-10-01

    The capability to remotely control the release of biomolecules provides an unique opportunity to monitor and regulate neural signaling, which spans extraordinary spatial and temporal scales. While various strategies, including local perfusion, molecular "uncaging", or photosensitive polymeric materials, have been applied to achieve controlled releasing of neuro-active substances, it is still challenging to adopt these technologies in many experimental contexts that require a straightforward but versatile loading-releasing mechanism. Here, we develop a synthetic strategy for remotely controllable releasing of neuro-modulating molecules. This platform is based on microscale composite hydrogels that incorporate polypyrrole (PPy) nanoparticles as photo-thermal transducers and is triggered by near-infrared-light (NIR) irradiation. Specifically, we first demonstrate the utility of our technology by recapitulating the "turning assay" and "collapse assay", which involve localized treatment of chemotactic factors (e.g. Netrin or Semaphorin 3A) to subcellular neural elements and have been extensively used in studying axonal pathfinding. On a network scale, the photo-sensitive microgels are also validated for light-controlled releasing of neurotransmitters (e.g. glutamate). A single NIR-triggered release is sufficient to change the dynamics of a cultured hippocampal neuron network. Taking the advantage of NIR's capability to penetrate deep into live tissue, this technology is further shown to work similarly well in vivo, which is evidenced by synchronized spiking activity in response to NIR-triggered delivery of glutamate in rat auditory cortex, demonstrating remote control of brain activity without any genetic modifications. Notably, our nano-composite microgels are capable of delivering various molecules, ranging from small chemicals to large proteins, without involving any crosslinking chemistry. Such great versatility and ease-of-use will likely make our optically-controlled delivery technology a general and important tool in cell biology research. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Prompt triggering of edge localized modes through lithium granule injection on EAST

    NASA Astrophysics Data System (ADS)

    Lunsford, Robert; Sun, Z.; Hu, J. S.; Xu, W.; Zuo, G. Z.; Gong, X. Z.; Wan, B. N.; Li, J. G.; Huang, M.; Maingi, R.; Diallo, A.; Tritz, K.; the EAST Team

    2017-10-01

    We report successful triggering of edge localized mode (ELMs) in EAST with Lithium (Li) micropellets, and the observed dependence of ELM triggering efficiency on granule size. ELM control is essential for successful ITER operation throughout the entire campaign, relying on magnetic perturbations for ELM suppression and ELM frequency enhancement via pellet injection. To separate the task of fueling from ELM pacing, we initiate the prompt generation of ELMs via impurity granule injection. Lithium granules ranging in size from 200 - 1000 microns are mechanically injected into upper-single null EAST long pulse H-mode discharges. The injections are monitored for their effect on high Z impurity accumulation and to assess the pressure perturbation required for reliable ELM triggering. We have determined that granules of diameter larger than 600 microns (corresponding to 5.2 x 1018 Li atoms) are successful at triggering ELMs more than 90% of the time. The triggering efficiency drops precipitously to less than 40% as the granule size is reduced to 400 microns (1.5 x 1018 Li atoms), indicating a triggering threshold has been crossed. Using this information an optimal impurity granule size which will regularly trigger a prompt ELM in these EAST discharges is determined. Coupling these results with alternate discharge scenarios on EAST and similar experiments performed on DIII-D provides the possibility of extrapolation to future devices.

  3. Triggering of frequent turbidity currents in Monterey Canyon and the role of antecedent conditioning

    NASA Astrophysics Data System (ADS)

    Clare, M. A.; Rosenberger, K. J.; Talling, P.; Barry, J.; Maier, K. L.; Parsons, D. R.; Simmons, S.; Gales, J. A.; Gwiazda, R.; McGann, M.; Paull, C. K.

    2017-12-01

    Turbidity currents pose a hazard to seafloor infrastructure, deliver organic carbon and nutrients to deep-sea communities, and form economically important deposits. Thus, determining the tempo of turbidity current activity and whether different triggers result in different flow modes is important. Identification of specific triggers is challenging, however, because most studies of turbidity currents are based on their deposits. New direct monitoring of flows and environmental conditions provides the necessary temporal constraints to identify triggering mechanisms. The Coordinated Canyon Experiment (CCE) in Monterey Canyon, offshore California is the most ambitious attempt yet to measure turbidity flows and their triggers. The CCE provides precise constraint on flow timing, initiation, and potential triggers based on measurements at 7 different instrumented moorings and 2 metocean buoys. Fifteen turbidity flows were measured in 18 months; with recorded velocities >8 m/s and run-outs of up to 50 km. Presence of live estuarine foraminifera within moored sediment traps suggests that that flows originated in water depths of <10 m, but it is unclear specifically how these flows were triggered. Turbidity currents are thought to be triggered by processes including earthquakes, river floods and storm waves. Here we analyse seismicity, local river discharge, internal tides, wave height, direction and period data. We identify no clear control of any of these individual variables on flow timing. None of the recorded earthquakes (

  4. Evaluation of Applicability of a Flare Trigger Model Based on a Comparison of Geometric Structures

    NASA Astrophysics Data System (ADS)

    Bamba, Yumi; Kusano, Kanya

    2018-03-01

    The triggering mechanism(s) and critical condition(s) of solar flares are still not completely clarified, although various studies have attempted to elucidate them. We have also proposed a theoretical flare-trigger model based on MHD simulations in which two types of small-scale bipole fields, the so-called opposite polarity (OP) and reversed shear (RS), can trigger flares. In this study, we evaluated the applicability of our flare-trigger model to the observation of 32 flares that were observed by the Solar Dynamics Observatory, by focusing on geometrical structures. We classified the events into six types, including the OP and RS types, based on photospheric magnetic field configuration, presence of precursor brightenings, and shape of the initial flare ribbons. As a result, we found that approximately 30% of the flares were consistent with our flare-trigger model, and the number of RS-type triggered flares is larger than that of the OP type. We found that none of the sampled events contradict our flare model; though, we cannot clearly determine the trigger mechanism of 70% of the flares in this study. We carefully investigated the applicability of our flare-trigger model and the possibility that other models can explain the other 70% of the events. Consequently, we concluded that our flare-trigger model has certainly proposed important conditions for flare-triggering.

  5. Respirator triggering of electron beam computed tomography (EBCT): evaluation of dynamic changes during mechanical expiration in the traumatized patient

    NASA Astrophysics Data System (ADS)

    Recheis, Wolfgang A.; Kleinsasser, Axel; Hatschenberger, Robert; Knapp, Rudolf; zur Nedden, Dieter; Hoermann, Christoph

    1999-05-01

    The purpose of this project is to evaluate the dynamic changes during expiration at different levels of positive end- expiratory pressure (PEEP) in the ventilated patient. We wanted to discriminate between normal lung function and acute respiratory distress syndrome (ARDS). After approval by the local Ethic Committee we studied two ventilated patients: (1) with normal lung function; (2) ARDS). We used the 50 ms scan mode of the EBCT. The beam was positioned 1 cm above the diaphragm. The table position remained unchanged. An electronic trigger was developed, that utilizes the respirators synchronizing signal to start the EBCT at the onset of expiration. During controlled mechanical expiration at two levels of PEEP (0 and 15 cm H2O), pulmonary aeration was rated as: well-aerated (-900HU/-500HU), poorly- aerated (-500HU/-100HU) and non-aerated (-100HU/+100HU). Pathological and normal lung function showed different dynamic changes (FIG.4-12). The different PEEP levels resulted in a significant change of pulmonary aeration in the same patient. Although we studied only a very limited number of patients, respirator triggered EBCT may be accurate in discriminating pathological changes due to the abnormal lung function in the mechanically ventilated patient.

  6. Synaptic vesicle recycling: steps and principles

    PubMed Central

    Rizzoli, Silvio O

    2014-01-01

    Synaptic vesicle recycling is one of the best-studied cellular pathways. Many of the proteins involved are known, and their interactions are becoming increasingly clear. However, as for many other pathways, it is still difficult to understand synaptic vesicle recycling as a whole. While it is generally possible to point out how synaptic reactions take place, it is not always easy to understand what triggers or controls them. Also, it is often difficult to understand how the availability of the reaction partners is controlled: how the reaction partners manage to find each other in the right place, at the right time. I present here an overview of synaptic vesicle recycling, discussing the mechanisms that trigger different reactions, and those that ensure the availability of reaction partners. A central argument is that synaptic vesicles bind soluble cofactor proteins, with low affinity, and thus control their availability in the synapse, forming a buffer for cofactor proteins. The availability of cofactor proteins, in turn, regulates the different synaptic reactions. Similar mechanisms, in which one of the reaction partners buffers another, may apply to many other processes, from the biogenesis to the degradation of the synaptic vesicle. PMID:24596248

  7. Protein addressing on patterned microchip by coupling chitosan electrodeposition and 'electro-click' chemistry.

    PubMed

    Shi, Xiao-Wen; Qiu, Ling; Nie, Zhen; Xiao, Ling; Payne, Gregory F; Du, Yumin

    2013-12-01

    Many applications in proteomics and lab-on-chip analysis require methods that guide proteins to assemble at surfaces with high spatial and temporal control. Electrical inputs are particularly convenient to control, and there has been considerable effort to discover simple and generic mechanisms that allow electrical inputs to trigger protein assembly on-demand. Here, we report the electroaddressing of a protein to a patterned surface by coupling two generic electroaddressing mechanisms. First, we electrodeposit the stimuli-responsive film-forming aminopolysaccharide chitosan to form a hydrogel matrix at the electrode surface. After deposition, the matrix is chemically functionalized with alkyne groups. Second, we ''electro-click' an azide-tagged protein to the functionalized matrix using electrical signals to trigger conjugation by Huisgen 1,3-dipolar cycloadditions. Specifically, a cathodic potential is applied to the matrix-coated electrode to reduce Cu(II) to Cu(I) which is required for the click reaction. Using fluorescently-labeled bovine serum albumin as our model, we demonstrate that protein conjugation can be controlled spatially and temporally. We anticipate that the coupling of polysaccharide electrodeposition and electro-click chemistry will provide a simple and generic approach to electroaddress proteins within compatible hydrogel matrices.

  8. Light-Triggered Release of DNA from Plasmon-Resonant Nanoparticles

    NASA Astrophysics Data System (ADS)

    Huschka, Ryan

    Plasmon-resonant nanoparticle complexes show promising potential for lighttriggered, controllable delivery of deoxyribonucleic acids (DNA) for research and therapeutic purposes. For example, the approach of RNA interference (RNAi) . using antisense DNA or RNA oligonucleotides to silence activity of a specific pathogenic gene transcript and reduce expression of the encoded protein . is very useful in dissecting genetic function and holds promise as a molecular therapeutic. Herein, we investigate the mechanism and probe the in vitro therapeutic potential of DNA light-triggered release from plasmonic nanoparticles. First, we investigate the mechanism of light-triggered release by dehybridizing double-stranded (dsDNA) via laser illumination from two types of nanoparticle substrates: gold (Au) nanoshells and Au nanorods. Both light-triggered and thermally induced releases are distinctly observable from nanoshell-based complexes. Surprisingly, no analogous measurable light-triggered release was observable from nanorod-based complexes below the DNA melting temperature. These results suggest that a nonthermal mechanism may play a role in light-triggered DNA release. Second, we demonstrate the in vitro light-triggered release of molecules noncovalently attached within dsDNA bound to the Au nanoshell surface. DAPI (4',6- diamidino-2-phenylindole), a bright blue fluorescent molecule that binds reversibly to double-stranded DNA, was chosen to visualize this intracellular light-induced release process. Illumination through the cell membrane of the nanoshell-dsDNA-DAPI complexes dehybridizes the DNA and releases the DAPI molecules within living cells. The DAPI molecules diffuse to the nucleus and associate with the cell's endogenous DNA. This work could have future applications towards drug delivery of molecules that associate with dsDNA. Finally, we demonstrate an engineered Au nanoshell (AuNS)-based therapeutic oligonucleotide delivery vehicle, designed to release its cargo on demand upon illumination with a near-infrared (NIR) laser. A poly(L)lysine peptide (PLL) epilayer coated onto the AuNS surface (AuNS-PLL) is used to capture intact, single-stranded antisense DNA oligonucleotide, or alternatively, double-stranded short-interfering RNA (siRNA) molecules. A green fluorescent protein (GFP)-expressing human lung cancer H1299 cell line was used to determine cellular uptake and GFP gene silencing mediated by AuNS-PLL delivery vector. The light-triggered release of oligonucleotides could have broad applications in the study of cellular processes and in the development of intracellular targeted therapies.

  9. Event-Based Robust Control for Uncertain Nonlinear Systems Using Adaptive Dynamic Programming.

    PubMed

    Zhang, Qichao; Zhao, Dongbin; Wang, Ding

    2018-01-01

    In this paper, the robust control problem for a class of continuous-time nonlinear system with unmatched uncertainties is investigated using an event-based control method. First, the robust control problem is transformed into a corresponding optimal control problem with an augmented control and an appropriate cost function. Under the event-based mechanism, we prove that the solution of the optimal control problem can asymptotically stabilize the uncertain system with an adaptive triggering condition. That is, the designed event-based controller is robust to the original uncertain system. Note that the event-based controller is updated only when the triggering condition is satisfied, which can save the communication resources between the plant and the controller. Then, a single network adaptive dynamic programming structure with experience replay technique is constructed to approach the optimal control policies. The stability of the closed-loop system with the event-based control policy and the augmented control policy is analyzed using the Lyapunov approach. Furthermore, we prove that the minimal intersample time is bounded by a nonzero positive constant, which excludes Zeno behavior during the learning process. Finally, two simulation examples are provided to demonstrate the effectiveness of the proposed control scheme.

  10. "The phactalysts": carbon nanotube/TiO2 composites as phototropic actuators for wireless remote triggering of chemical reactions and catalysis.

    PubMed

    Vassalini, Irene; Alessandri, Ivano

    2017-08-17

    A new concept of a reconfigurable smart catalyst was developed from the synergistic combination of polycarbonate/carbon nanotube bimorph photoactuators and TiO 2 . The addition of TiO 2 provides the photoactuators with photocatalytic activity and superior opto-mechanical properties, making phototropic actuation fast, reversible and responsive to Vis-NIR light sources. These composites were tested in the wireless, light-driven and spatially controlled remote triggering of different chemical reactions, including local explosions and photocatalytic polymerizations. The same materials were also investigated as efficient opto-mechanical shutters for the light-selective inhibition or activation of specific reactions, such as the photo-induced degradation of organic dyes. These results suggest that the integration of photocatalysts with soft photoactuators can open intriguing opportunities for chemistry and soft robotics.

  11. Molecular Mechanisms of Root Gravitropism.

    PubMed

    Su, Shih-Heng; Gibbs, Nicole M; Jancewicz, Amy L; Masson, Patrick H

    2017-09-11

    Plant shoots typically grow against the gravity vector to access light, whereas roots grow downward into the soil to take up water and nutrients. These gravitropic responses can be altered by developmental and environmental cues. In this review, we discuss the molecular mechanisms that govern the gravitropism of angiosperm roots, where a physical separation between sites for gravity sensing and curvature response has facilitated discovery. Gravity sensing takes place in the columella cells of the root cap, where sedimentation of starch-filled plastids (amyloplasts) triggers a pathway that results in a relocalization to the lower side of the cell of PIN proteins, which facilitate efflux of the plant hormone auxin efflux. Consequently, auxin accumulates in the lower half of the root, triggering bending of the root tip at the elongation zone. We review our understanding of the molecular mechanisms that control this process in primary roots, and discuss recent insights into the regulation of oblique growth in lateral roots and its impact on root-system architecture and soil exploration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Relating triggering processes in lab experiments with earthquakes.

    NASA Astrophysics Data System (ADS)

    Baro Urbea, J.; Davidsen, J.; Kwiatek, G.; Charalampidou, E. M.; Goebel, T.; Stanchits, S. A.; Vives, E.; Dresen, G.

    2016-12-01

    Statistical relations such as Gutenberg-Richter's, Omori-Utsu's and the productivity of aftershocks were first observed in seismology, but are also common to other physical phenomena exhibiting avalanche dynamics such as solar flares, rock fracture, structural phase transitions and even stock market transactions. All these examples exhibit spatio-temporal correlations that can be explained as triggering processes: Instead of being activated as a response to external driving or fluctuations, some events are consequence of previous activity. Although different plausible explanations have been suggested in each system, the ubiquity of such statistical laws remains unknown. However, the case of rock fracture may exhibit a physical connection with seismology. It has been suggested that some features of seismology have a microscopic origin and are reproducible over a vast range of scales. This hypothesis has motivated mechanical experiments to generate artificial catalogues of earthquakes at a laboratory scale -so called labquakes- and under controlled conditions. Microscopic fractures in lab tests release elastic waves that are recorded as ultrasonic (kHz-MHz) acoustic emission (AE) events by means of piezoelectric transducers. Here, we analyse the statistics of labquakes recorded during the failure of small samples of natural rocks and artificial porous materials under different controlled compression regimes. Temporal and spatio-temporal correlations are identified in certain cases. Specifically, we distinguish between the background and triggered events, revealing some differences in the statistical properties. We fit the data to statistical models of seismicity. As a particular case, we explore the branching process approach simplified in the Epidemic Type Aftershock Sequence (ETAS) model. We evaluate the empirical spatio-temporal kernel of the model and investigate the physical origins of triggering. Our analysis of the focal mechanisms implies that the occurrence of the empirical laws extends well beyond purely frictional sliding events, in contrast to what is often assumed.

  13. Output Consensus of Heterogeneous Linear Multi-Agent Systems by Distributed Event-Triggered/Self-Triggered Strategy.

    PubMed

    Hu, Wenfeng; Liu, Lu; Feng, Gang

    2016-09-02

    This paper addresses the output consensus problem of heterogeneous linear multi-agent systems. We first propose a novel distributed event-triggered control scheme. It is shown that, with the proposed control scheme, the output consensus problem can be solved if two matrix equations are satisfied. Then, we further propose a novel self-triggered control scheme, with which continuous monitoring is avoided. By introducing a fixed timer into both event- and self-triggered control schemes, Zeno behavior can be ruled out for each agent. The effectiveness of the event- and self-triggered control schemes is illustrated by an example.

  14. Strategic modulation of cognitive control.

    PubMed

    Lungu, Ovidiu V; Liu, Tao; Waechter, Tobias; Willingham, Daniel T; Ashe, James

    2007-08-01

    The neural substrate of cognitive control is thought to comprise an evaluative component located in the anterior cingulate cortex (ACC) and an executive component in the prefrontal cortex (PFC). The control mechanism itself is mainly local, triggered by response conflict (monitored by the ACC) and involving the allocation of executive resources (recruited by the PFC) in a trial-to-trial fashion. However, another way to achieve control would be to use a strategic mechanism based on long-term prediction of upcoming events and on a chronic response strategy that ignores local features of the task. In the current study, we showed that such a strategic control mechanism was based on a functional dissociation or complementary relationship between the ACC and the PFC. When information in the environment was available to make predictions about upcoming stimuli, local task features (e.g., response conflict) were no longer used as a control signal. We suggest that having separate control mechanisms based on local or global task features allows humans to be persistent in pursuing their goals, yet flexible enough to adapt to changes in the environment.

  15. Asthma Triggers: Gain Control

    MedlinePlus

    ... Centers Asthma Contact Us Share Asthma Triggers: Gain Control Breathing Freely: Controlling Asthma Triggers This video features ... Air Quality: Biological Pollutants Help Your Child Gain Control Over Asthma Top of Page Molds About Molds ...

  16. Anticipating conflict facilitates controlled stimulus-response selection

    PubMed Central

    Correa, Ángel; Rao, Anling; Nobre, Anna C.

    2014-01-01

    Cognitive control can be triggered in reaction to previous conflict, as suggested by the finding of sequential effects in conflict tasks. Can control also be triggered proactively by presenting cues predicting conflict (‘proactive control’)? We exploited the high temporal resolution of event-related potentials (ERPs) and controlled for sequential effects to ask whether proactive control based on anticipating conflict modulates neural activity related to cognitive control, as may be predicted from the conflict-monitoring model. ERPs associated with conflict detection (N2) were measured during a cued flanker task. Symbolic cues were either informative or neutral with respect to whether the target involved conflicting or congruent responses. Sequential effects were controlled by analysing the congruency of the previous trial. The results showed that cuing conflict facilitated conflict resolution and reduced the N2 latency. Other potentials (frontal N1 and P3) were also modulated by cuing conflict. Cuing effects were most evident after congruent than after incongruent trials. This interaction between cuing and sequential effects suggests neural overlap between the control networks triggered by proactive and reactive signals. This finding clarifies why previous neuroimaging studies, in which reactive sequential effects were not controlled, have rarely found anticipatory effects upon conflict-related activity. Finally, the high temporal resolution of ERPs was critical to reveal a temporal modulation of conflict detection by proactive control. This novel finding suggests that anticipating conflict speeds up conflict detection and resolution. Recent research suggests that this anticipatory mechanism may be mediated by pre-activation of the ACC during the preparatory interval. PMID:18823248

  17. Experimental Investigation of Mechanical Behavior of an Oxide/Oxide Ceramic Composite in Interlaminar Shear and under Combined Tension-Torsion Loading

    DTIC Science & Technology

    2014-03-27

    testing machine was warmed up for at least 30 min using a cyclic command with a sine waveform in displacement control . Gripping sections of each test...the test specimen was inserted into the susceptor. Then the testing machine is placed in displacement control and the top portion of the specimen...the MTS software also triggered the operation of the high speed cameras. 31 The testing system was placed in displacement /rotation control and the

  18. Asynchronous data change notification between database server and accelerator controls system

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

    Fu, W.; Morris, J.; Nemesure, S.

    2011-10-10

    Database data change notification (DCN) is a commonly used feature. Not all database management systems (DBMS) provide an explicit DCN mechanism. Even for those DBMS's which support DCN (such as Oracle and MS SQL server), some server side and/or client side programming may be required to make the DCN system work. This makes the setup of DCN between database server and interested clients tedious and time consuming. In accelerator control systems, there are many well established software client/server architectures (such as CDEV, EPICS, and ADO) that can be used to implement data reflection servers that transfer data asynchronously to anymore » client using the standard SET/GET API. This paper describes a method for using such a data reflection server to set up asynchronous DCN (ADCN) between a DBMS and clients. This method works well for all DBMS systems which provide database trigger functionality. Asynchronous data change notification (ADCN) between database server and clients can be realized by combining the use of a database trigger mechanism, which is supported by major DBMS systems, with server processes that use client/server software architectures that are familiar in the accelerator controls community (such as EPICS, CDEV or ADO). This approach makes the ADCN system easy to set up and integrate into an accelerator controls system. Several ADCN systems have been set up and used in the RHIC-AGS controls system.« less

  19. Cyclin B Translation Depends on mTOR Activity after Fertilization in Sea Urchin Embryos

    PubMed Central

    Boulben, Sandrine; Glippa, Virginie; Morales, Julia; Cormier, Patrick

    2016-01-01

    The cyclin B/CDK1 complex is a key regulator of mitotic entry. Using PP242, a specific ATP-competitive inhibitor of mTOR kinase, we provide evidence that the mTOR signalling pathway controls cyclin B mRNA translation following fertilization in Sphaerechinus granularis and Paracentrotus lividus. We show that PP242 inhibits the degradation of the cap-dependent translation repressor 4E-BP (eukaryotic initiation factor 4E-Binding Protein). PP242 inhibits global protein synthesis, delays cyclin B accumulation, cyclin B/CDK1 complex activation and consequently entry into the mitotic phase of the cell cycle triggered by fertilization. PP242 inhibits cyclin B mRNA recruitment into active polysomes triggered by fertilization. An amount of cyclin B mRNA present in active polysomes appears to be insensitive to PP242 treatment. Taken together, our results suggest that, following sea urchin egg fertilization, cyclin B mRNA translation is controlled by two independent mechanisms: a PP242-sensitive and an additional PP242-insentitive mechanism. PMID:26962866

  20. Near-Infrared-Induced Heating of Confined Water in Polymeric Particles for Efficient Payload Release

    PubMed Central

    2015-01-01

    Near-infrared (NIR) light-triggered release from polymeric capsules could make a major impact on biological research by enabling remote and spatiotemporal control over the release of encapsulated cargo. The few existing mechanisms for NIR-triggered release have not been widely applied because they require custom synthesis of designer polymers, high-powered lasers to drive inefficient two-photon processes, and/or coencapsulation of bulky inorganic particles. In search of a simpler mechanism, we found that exposure to laser light resonant with the vibrational absorption of water (980 nm) in the NIR region can induce release of payloads encapsulated in particles made from inherently non-photo-responsive polymers. We hypothesize that confined water pockets present in hydrated polymer particles absorb electromagnetic energy and transfer it to the polymer matrix, inducing a thermal phase change. In this study, we show that this simple and highly universal strategy enables instantaneous and controlled release of payloads in aqueous environments as well as in living cells using both pulsed and continuous wavelength lasers without significant heating of the surrounding aqueous solution. PMID:24717072

  1. Near-infrared-induced heating of confined water in polymeric particles for efficient payload release.

    PubMed

    Viger, Mathieu L; Sheng, Wangzhong; Doré, Kim; Alhasan, Ali H; Carling, Carl-Johan; Lux, Jacques; de Gracia Lux, Caroline; Grossman, Madeleine; Malinow, Roberto; Almutairi, Adah

    2014-05-27

    Near-infrared (NIR) light-triggered release from polymeric capsules could make a major impact on biological research by enabling remote and spatiotemporal control over the release of encapsulated cargo. The few existing mechanisms for NIR-triggered release have not been widely applied because they require custom synthesis of designer polymers, high-powered lasers to drive inefficient two-photon processes, and/or coencapsulation of bulky inorganic particles. In search of a simpler mechanism, we found that exposure to laser light resonant with the vibrational absorption of water (980 nm) in the NIR region can induce release of payloads encapsulated in particles made from inherently non-photo-responsive polymers. We hypothesize that confined water pockets present in hydrated polymer particles absorb electromagnetic energy and transfer it to the polymer matrix, inducing a thermal phase change. In this study, we show that this simple and highly universal strategy enables instantaneous and controlled release of payloads in aqueous environments as well as in living cells using both pulsed and continuous wavelength lasers without significant heating of the surrounding aqueous solution.

  2. Early T-cell activation biophysics

    PubMed Central

    Henry, Nelly; Hivroz, Claire

    2009-01-01

    The T-cell is one of the main players in the mammalian immune response. It ensures antigen recognition at the surface of antigen-presenting cells in a complex and highly sensitive and specific process, in which the encounter of the T-cell receptor with the agonist peptide associated with the major histocompatibility complex triggers T-cell activation. While signaling pathways have been elucidated in increasing detail, the mechanism of TCR triggering remains highly controversial despite active research published in the past 10 years. In this paper, we present a short overview of pending questions on critical initial events associated with T-cell triggering. In particular, we examine biophysical approaches already in use, as well as future directions. We suggest that the most recent advances in fluorescence super-resolution imaging, coupled with the new classes of genetic fluorescent probes, will play an important role in elucidation of the T-cell triggering mechanism. Beyond this aspect, we predict that exploration of mechanical cues in the triggering process will provide new clues leading to clarification of the entire mechanism. PMID:20514131

  3. Explosion suppression system

    DOEpatents

    Sapko, Michael J.; Cortese, Robert A.

    1992-01-01

    An explosion suppression system and triggering apparatus therefor are provided for quenching gas and dust explosions. An electrically actuated suppression mechanism which dispenses an extinguishing agent into the path ahead of the propagating flame is actuated by a triggering device which is light powered. This triggering device is located upstream of the propagating flame and converts light from the flame to an electrical actuation signal. A pressure arming device electrically connects the triggering device to the suppression device only when the explosion is sensed by a further characteristic thereof beside the flame such as the pioneer pressure wave. The light powered triggering device includes a solar panel which is disposed in the path of the explosion and oriented between horizontally downward and vertical. Testing mechanisms are also preferably provided to test the operation of the solar panel and detonator as well as the pressure arming mechanism.

  4. The failure of earthquake failure models

    USGS Publications Warehouse

    Gomberg, J.

    2001-01-01

    In this study I show that simple heuristic models and numerical calculations suggest that an entire class of commonly invoked models of earthquake failure processes cannot explain triggering of seismicity by transient or "dynamic" stress changes, such as stress changes associated with passing seismic waves. The models of this class have the common feature that the physical property characterizing failure increases at an accelerating rate when a fault is loaded (stressed) at a constant rate. Examples include models that invoke rate state friction or subcritical crack growth, in which the properties characterizing failure are slip or crack length, respectively. Failure occurs when the rate at which these grow accelerates to values exceeding some critical threshold. These accelerating failure models do not predict the finite durations of dynamically triggered earthquake sequences (e.g., at aftershock or remote distances). Some of the failure models belonging to this class have been used to explain static stress triggering of aftershocks. This may imply that the physical processes underlying dynamic triggering differs or that currently applied models of static triggering require modification. If the former is the case, we might appeal to physical mechanisms relying on oscillatory deformations such as compaction of saturated fault gouge leading to pore pressure increase, or cyclic fatigue. However, if dynamic and static triggering mechanisms differ, one still needs to ask why static triggering models that neglect these dynamic mechanisms appear to explain many observations. If the static and dynamic triggering mechanisms are the same, perhaps assumptions about accelerating failure and/or that triggering advances the failure times of a population of inevitable earthquakes are incorrect.

  5. Orthogonal Operation of Constitutional Dynamic Networks Consisting of DNA-Tweezer Machines.

    PubMed

    Yue, Liang; Wang, Shan; Cecconello, Alessandro; Lehn, Jean-Marie; Willner, Itamar

    2017-12-26

    Overexpression or down-regulation of cellular processes are often controlled by dynamic chemical networks. Bioinspired by nature, we introduce constitutional dynamic networks (CDNs) as systems that emulate the principle of the nature processes. The CDNs comprise dynamically interconvertible equilibrated constituents that respond to external triggers by adapting the composition of the dynamic mixture to the energetic stabilization of the constituents. We introduce a nucleic acid-based CDN that includes four interconvertible and mechanically triggered tweezers, AA', BB', AB' and BA', existing in closed, closed, open, and open configurations, respectively. By subjecting the CDN to auxiliary triggers, the guided stabilization of one of the network constituents dictates the dynamic reconfiguration of the structures of the tweezers constituents. The orthogonal and reversible operations of the CDN DNA tweezers are demonstrated, using T-A·T triplex or K + -stabilized G-quadruplex as structural motifs that control the stabilities of the constituents. The implications of the study rest on the possible applications of input-guided CDN assemblies for sensing, logic gate operations, and programmed activation of molecular machines.

  6. Dual-mode disturbance-accommodating pointing controller for Hubble Space Telescope

    NASA Astrophysics Data System (ADS)

    Addington, Stewart I.; Johnson, C. D.

    1995-03-01

    Cyclic thermal expansions and mechanical stiction effects in the solar arrays on the Hubble Space Telescope (HST) are triggering repeated occurrences of damped, relaxation-type flex-body vibrations of the solar arrays. Those solar array vibrations are, in turn, causing unwanted deviations of the telescope from its specified pointing direction. In this paper we propose two strategies one can adopt in designing a telescope-pointing controller to cope with the aforementioned disturbances: 1) a total isolation (TI) control strategy whereby the HST controller torques are designed to adaptively counteract and cancel out the persistent disturbing torques that are causing the unwanted telescope motions and 2) an array damping (AD) control strategy whereby the HST controller torques are used to actively augment the natural dampening of the solar array vibrations and the attendant telescope motions, between triggerings of the stiction-related flex-body relaxation oscillations. Using the principles of disturbance accommodation control theory, a dual-mode controller for a generic, planar-motion (single-axis) model of the HST is proposed. This controller incorporates both the TI and AD modes of disturbance accommodation. Simulation studies of the closed-loop system using generic parameter values clearly indicate, qualitatively, the enhanced pointing performance such a controller can achieve.

  7. Nickel (II) nitrate hexahydrate triggered canine neutrophil extracellular traps release in vitro.

    PubMed

    Wei, Zhengkai; Zhang, Xu; Wang, Yanan; Wang, Jingjing; Fu, Yunhe; Yang, Zhengtao

    2018-05-30

    Nickel (II) nitrate hexahydrate (Ni) is a common heavy metal material in battery manufacturing, electroplating alloy parts and ceramic staining, therefore we frequently contact with Ni-related products in daily life. In this study, we aimed to investigate the effects of Ni on neutrophils extracellular traps (NETs) release by canine polymorphonuclear neutrophils (PMNs). The structure of Ni-induced NETs was observed by fluorescence confocal microscopy. Ni-triggered NETs release was quantified by Pico Green ® and fluorescence microplate reader. In addition, the inhibitors of NADPH oxidase, ERK1/2-, p38 - signaling pathways were used for preliminary inquiry into the potential mechanism of this process. The results showed that Ni markedly triggered the formation of NETs-like structures, and these structures were mainly consisted of DNA decorated with NE and MPO. Furthermore, quantification experiments showed that Ni significantly increased NETs formation compared to control groups. These results forcefully confirmed that nickel nitrate possesses the ability to induce NETs formation. However, inhibiting the NADPH oxidase, ERK1/2- and p38 MAPK-signaling pathways did not significantly change the quantitation of Ni-induced NETs release. To our knowledge, this study is the first report of Ni-triggered NETs release in vitro, which might provide an entirely new mechanism of several diseases and health issues induced by nickel overexposure. Copyright © 2018. Published by Elsevier Ltd.

  8. Dynamic Aftershock Triggering Correlated with Cyclic Loading in the Slip Direction

    NASA Astrophysics Data System (ADS)

    Hardebeck, J.

    2014-12-01

    Dynamic stress changes have been shown to contribute to aftershock triggering, but the physical triggering mechanisms are not fully understood. Some proposed mechanisms are based on dynamic stress loading of the target fault in a direction that encourages earthquake slip (e.g. dynamic Coulomb stress triggering), while other mechanisms are based on fault weakening due to shaking. If dynamic stress loading in the fault slip direction plays a role in aftershock triggering, we would expect to see a relationship between the dynamic stress orientations and the aftershock focal mechanisms. Alternatively, if dynamic stress change triggering functions only through a fault weakening mechanism that is independent of the slip direction of the target fault, no such relationship is expected. I study aftershock sequences of 4 M≥6.7 mainshocks in southern California, and find a small but significant relationship between modeled dynamic stress direction and aftershock focal mechanisms. The mainshock dynamic stress changes have two observed impacts: changing the focal mechanisms in a given location to favor those aligned with the dynamic stress change, and changing the spatial distribution of seismicity to favor locations where the dynamic stress change aligns with the background stress. The aftershock focal mechanisms are significantly more aligned with the dynamic stress changes than the preshock mechanisms for only the first 0.5-1 year following most mainshocks, although for at least 10 years following Hector Mine. Dynamic stress effects on focal mechanisms are best observed at long periods (30-60 sec). Dynamic stress effects are only observed when using metrics based on repeated stress cycling in the same direction, for example considering the dominant stress orientation over the full time series, and not for the peak dynamic stress. These results imply that dynamic aftershock triggering operates at least in part through cyclic loading in the direction of fault slip, although non-directional fault weakening may be important as well. This suggests that the orientation of the dynamic stresses, as well as their amplitude, should be considered in the development of physics-based aftershock forecasting models.

  9. A Trigger Mechanism for Volcanic Low-Frequency Seismic Events on Montserrat

    NASA Astrophysics Data System (ADS)

    Neuberg, J. W.; Tuffen, H.; Jolly, A.; Green, D.

    2003-12-01

    Seismic observations of low-frequency earthquake swarms on Montserrat point to a non-destructive, repeatable source mechanism in a confined area inside or near the conduit. While the seismic wave propagation pattern of the subsequent resonance in and around the conduit is well studied, the trigger mechanism has remained elusive. In this contribution we suggest a trigger mechanism based on new field evidence for fracture and healing of magma in volcanic conduits, together with seismic observations from Montserrat and finite element modelling of magma deformation during conduit flow. As a seismic trigger we suggest a stick-slip motion of highly-viscous magma in the glass transition, that periodically generates networks of seismogenic shear fractures a few metres in length. These fractures are rapidly filled by fine-grained material [cataclasite] that is generated by friction processes on the fracture surfaces, such as corner abrasion, and is locally redeposited by gas flowing within the fracture system. Filled fractures are then swiftly healed as reloading leads to annealing and a return to cohesive viscous deformation. Such a fast healing process, probably on the order of tens of seconds, leads to a repeatable trigger mechanism. Due to a strong lateral viscosity gradient in the conduit, highly-viscous magma near the conduit walls, which can exhibit brittle behaviour, co-exists with low-viscosity, fluid magma in the conduit centre; such that brittle failure provides the seismic trigger mechanism while the fluid part can still act as a seismic resonator.

  10. The development of high-voltage repetitive low-jitter corona stabilized triggered switch

    NASA Astrophysics Data System (ADS)

    Geng, Jiuyuan; Yang, Jianhua; Cheng, Xinbing; Yang, Xiao; Chen, Rong

    2018-04-01

    The high-power switch plays an important part in a pulse power system. With the trend of pulse power technology toward modularization, miniaturization, and accuracy control, higher requirements on electrical trigger and jitter of the switch have been put forward. A high-power low-jitter corona-stabilized triggered switch (CSTS) is designed in this paper. This kind of CSTS is based on corona stabilized mechanism, and it can be used as a main switch of an intense electron-beam accelerator (IEBA). Its main feature was the use of an annular trigger electrode instead of a traditional needle-like trigger electrode, taking main and side trigger rings to fix the discharging channels and using SF6/N2 gas mixture as its operation gas. In this paper, the strength of the local field enhancement was changed by a trigger electrode protrusion length Dp. The differences of self-breakdown voltage and its stability, delay time jitter, trigger requirements, and operation range of the switch were compared. Then the effect of different SF6/N2 mixture ratio on switch performance was explored. The experimental results show that when the SF6 is 15% with the pressure of 0.2 MPa, the hold-off voltage of the switch is 551 kV, the operating range is 46.4%-93.5% of the self-breakdown voltage, the jitter is 0.57 ns, and the minimum trigger voltage requirement is 55.8% of the peak. At present, the CSTS has been successfully applied to an IEBA for long time operation.

  11. The development of high-voltage repetitive low-jitter corona stabilized triggered switch.

    PubMed

    Geng, Jiuyuan; Yang, Jianhua; Cheng, Xinbing; Yang, Xiao; Chen, Rong

    2018-04-01

    The high-power switch plays an important part in a pulse power system. With the trend of pulse power technology toward modularization, miniaturization, and accuracy control, higher requirements on electrical trigger and jitter of the switch have been put forward. A high-power low-jitter corona-stabilized triggered switch (CSTS) is designed in this paper. This kind of CSTS is based on corona stabilized mechanism, and it can be used as a main switch of an intense electron-beam accelerator (IEBA). Its main feature was the use of an annular trigger electrode instead of a traditional needle-like trigger electrode, taking main and side trigger rings to fix the discharging channels and using SF 6 /N 2 gas mixture as its operation gas. In this paper, the strength of the local field enhancement was changed by a trigger electrode protrusion length Dp. The differences of self-breakdown voltage and its stability, delay time jitter, trigger requirements, and operation range of the switch were compared. Then the effect of different SF 6 /N 2 mixture ratio on switch performance was explored. The experimental results show that when the SF 6 is 15% with the pressure of 0.2 MPa, the hold-off voltage of the switch is 551 kV, the operating range is 46.4%-93.5% of the self-breakdown voltage, the jitter is 0.57 ns, and the minimum trigger voltage requirement is 55.8% of the peak. At present, the CSTS has been successfully applied to an IEBA for long time operation.

  12. Autophagy as a trigger for cell death: autophagic degradation of inhibitor of apoptosis dBruce controls DNA fragmentation during late oogenesis in Drosophila.

    PubMed

    Nezis, Ioannis P; Shravage, Bhupendra V; Sagona, Antonia P; Johansen, Terje; Baehrecke, Eric H; Stenmark, Harald

    2010-11-01

    Autophagy has been reported to contribute to cell death, but the underlying mechanisms remain largely unknown and controversial. We have: been studying oogenesis in Drosophila melanogaster as a model system to understand the interplay between autophagy and cell death. Using a novel autophagy reporter we found that autophagy occurs during developmental cell death of nurse cells in late oogenesis. Genetic inhibition: of autophagy-related genes atg1, atg13 and vps34 results in late-stage egg chambers containing persisting nurse cell nuclei without fragmented DNA and attenuation of caspase-3 cleavage. We found that Drosophila inhibitor of apoptosis dBruce is degraded by autophagy and this degradation promotes DNA fragmentation and subsequent nurse cell death. These studies demonstrate that autophagic degradation of an inhibitor: of apoptosis is a novel mechanism of triggering cell death.

  13. Variability of Tidal Volume in Patient-Triggered Mechanical Ventilation in ARDS.

    PubMed

    Perinel-Ragey, Sophie; Baboi, Loredana; Guérin, Claude

    2017-11-01

    Limiting tidal volume (V T ) in patients with ARDS may not be achieved once patient-triggered breaths occur. Furthermore, ICU ventilators offer numerous patient-triggered modes that work differently across brands. We systematically investigated, using a bench model, the effect of patient-triggered modes on the size and variability of V T at different breathing frequencies (f), patient effort, and ARDS severity. We used a V500 Infinity ICU ventilator connected to an ASL 5000 lung model whose compliance was mimicking mild, moderate, and severe ARDS. Thirteen patient-triggered modes were tested, falling into 3 categories, namely volume control ventilation with mandatory minute ventilation; pressure control ventilation, including airway pressure release ventilation (APRV); and pressure support ventilation. Two levels of f and effort were tested for each ARDS severity in each mode. Median (first-third quartiles) V T was compared across modes using non-parametric tests. The probability of V T > 6 mL/kg ideal body weight was assessed by binomial regression and expressed as the odds ratio (OR) with 95% CI. V T variability was measured from the coefficient of variation. V T distribution over all f, effort, and ARDS categories significantly differed across modes ( P < .001, Kruskal-Wallis test). V T was significantly greater with pressure support (OR 420 mL, 95% CI 332-527 mL) than with any other mode except for variable pressure support level. Risk for V T to be > 6 mL/kg was significantly increased with spontaneous breaths patient-triggered by pressure support (OR 19.36, 95% CI 12.37-30.65) and significantly reduced in APRV (OR 0.44, 95% CI 0.26-0.72) and pressure support with guaranteed volume mode. The risk increased with increasing effort and decreasing f. Coefficient of variation of V T was greater for low f and volume control-mandatory minute ventilation and pressure control modes. APRV had the greatest within-mode variability. Risk of V T > 6 mL/kg was significantly reduced in APRV and pressure support with guaranteed volume mode. APRV had the highest variability. Pressure support with guaranteed volume could be tested in patients with ARDS. Copyright © 2017 by Daedalus Enterprises.

  14. Power-law rheology controls aftershock triggering and decay

    PubMed Central

    Zhang, Xiaoming; Shcherbakov, Robert

    2016-01-01

    The occurrence of aftershocks is a signature of physical systems exhibiting relaxation phenomena. They are observed in various natural or experimental systems and usually obey several non-trivial empirical laws. Here we consider a cellular automaton realization of a nonlinear viscoelastic slider-block model in order to infer the physical mechanisms of triggering responsible for the occurrence of aftershocks. We show that nonlinear viscoelasticity plays a critical role in the occurrence of aftershocks. The model reproduces several empirical laws describing the statistics of aftershocks. In case of earthquakes, the proposed model suggests that the power-law rheology of the fault gauge, underlying lower crust, and upper mantle controls the decay rate of aftershocks. This is verified by analysing several prominent aftershock sequences for which the rheological properties of the underlying crust and upper mantle were established. PMID:27819355

  15. ADAPTIVE MECHANISMS CONTROLLING UTERINE SPIRAL ARTERY REMODELING DURING THE ESTABLISHMENT OF PREGNANCY

    PubMed Central

    Soares, Michael J.; Chakraborty, Damayanti; Kubota, Kaiyu; Renaud, Stephen J.; Rumi, M.A. Karim

    2015-01-01

    Implantation of the embryo into the uterus triggers the initiation of hemochorial placentation. The hemochorial placenta facilitates the acquisition of maternal resources required for embryo/fetal growth. Uterine spiral arteries form the nutrient supply line for the placenta and fetus. This vascular conduit undergoes gestation stage-specific remodeling directed by maternal natural killer cells and embryo-derived invasive trophoblast lineages. The placentation site, including remodeling of the uterine spiral arteries, is shaped by environmental challenges. In this review, we discuss the cellular participants controlling pregnancy-dependent uterine spiral artery remodeling and mechanisms responsible for their development and function. PMID:25023691

  16. Cdk1 phosphorylates SPAT-1/Bora to trigger PLK-1 activation and drive mitotic entry in C. elegans embryos

    PubMed Central

    Tavernier, Nicolas; Noatynska, Anna; Panbianco, Costanza; Martino, Lisa; Van Hove, Lucie; Schwager, Françoise; Léger, Thibaut

    2015-01-01

    The molecular mechanisms governing mitotic entry during animal development are incompletely understood. Here, we show that the mitotic kinase CDK-1 phosphorylates Suppressor of Par-Two 1 (SPAT-1)/Bora to regulate its interaction with PLK-1 and to trigger mitotic entry in early Caenorhabditis elegans embryos. Embryos expressing a SPAT-1 version that is nonphosphorylatable by CDK-1 and that is defective in PLK-1 binding in vitro present delays in mitotic entry, mimicking embryos lacking SPAT-1 or PLK-1 functions. We further show that phospho–SPAT-1 activates PLK-1 by triggering phosphorylation on its activator T loop in vitro by Aurora A. Likewise, we show that phosphorylation of human Bora by Cdk1 promotes phosphorylation of human Plk1 by Aurora A, suggesting that this mechanism is conserved in humans. Our results suggest that CDK-1 activates PLK-1 via SPAT-1 phosphorylation to promote entry into mitosis. We propose the existence of a positive feedback loop that connects Cdk1 and Plk1 activation to ensure a robust control of mitotic entry and cell division timing. PMID:25753036

  17. Shear-rate-dependent strength control on the dynamics of rainfall-triggered landslides, Tokushima Prefecture, Japan

    USGS Publications Warehouse

    Wang, G.; Suemine, A.; Schulz, W.H.

    2010-01-01

    A typhoon (Typhoon No. 10) attacked Shikoku Island and the Tyugoku area of Japan in 2004. This typhoon produced a new daily precipitation record of 1317 mm on Shikoku Island and triggered hundreds of landslides in Tokushima Prefecture. One catastrophic landslide was triggered in the Shiraishi area of Kisawa village, and destroyed more than 10 houses while also leaving an unstable block high on the slope. The unstable block kept moving after the event, showing accelerating and decelerating movement during and after rainfall and reaching a displacement of several meters before countermeasures were put into place. To examine the mechanism for this landsliding characteristic, samples (weathered serpentinite) were taken from the field, and their shear behaviours examined using ring shear tests. The test results revealed that the residual shear strength of the samples is positively dependent on the shear rate, which may provide an explanation for the continuous acceleratingdecelerating process of the landsliding. The roughness of the shear surface and the microstructure of the shear zone were measured and observed by laser microscope and SEM techniques in an attempt to clarify the mechanism of shear rate effect on the residual shear strength. Copyright ?? 2010 John Wiley & Sons, Ltd.

  18. Potassium dynamics and seizures: Why is potassium ictogenic?

    PubMed

    de Curtis, Marco; Uva, Laura; Gnatkovsky, Vadym; Librizzi, Laura

    2018-07-01

    Potassium channels dysfunction and altered genes encoding for molecules involved in potassium homeostasis have been associated with human epilepsy. These observations are in agreement with a control role of extracellular potassium on neuronal excitability and seizure generation. Epileptiform activity, in turn, regulates potassium homeostasis through mechanisms that are still not well established. We review here how potassium-associated processes are regulated in the brain and examine the mechanisms that support the role of potassium in triggering epileptiform activities. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Dual-stage periodic event-triggered output-feedback control for linear systems.

    PubMed

    Ruan, Zhen; Chen, Wu-Hua; Lu, Xiaomei

    2018-05-01

    This paper proposes an event-triggered control framework, called dual-stage periodic event-triggered control (DSPETC), which unifies periodic event-triggered control (PETC) and switching event-triggered control (SETC). Specifically, two period parameters h 1 and h 2 are introduced to characterize the new event-triggering rule, where h 1 denotes the sampling period, while h 2 denotes the monitoring period. By choosing some specified values of h 2 , the proposed control scheme can reduce to PETC or SETC scheme. In the DSPETC framework, the controlled system is represented as a switched system model and its stability is analyzed via a switching-time-dependent Lyapunov functional. Both the cases with/without network-induced delays are investigated. Simulation and experimental results show that the DSPETC scheme is superior to the PETC scheme and the SETC scheme. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

  20. Infrared-actuated recovery of polyurethane filled by reduced graphene oxide/carbon nanotube hybrids with high energy density.

    PubMed

    Feng, Yiyu; Qin, Mengmeng; Guo, Haiqiang; Yoshino, Katsumi; Feng, Wei

    2013-11-13

    Optically actuated shape recovery materials receive much interest because of their great ability to control the creation of mechanical motion remotely and precisely. An infrared (IR) triggered actuator based on shape recovery was fabricated using polyurethane (TPU) incorporated by sulfonated reduced graphene oxide (SRGO)/sulfonated carbon nanotube (SCNT) hybrid nanofillers. Interconnected SRGO/SCNT hybrid nanofillers at a low weight loading of 1% dispersed in TPU showed good IR absorption and improved the crystallization of soft segments for a large shape deformation. The output force, energy density and recovery time of IR-triggered actuators were dependent on weight ratios of SRGO to SCNT (SRGO:SCNT). TPU nanocomposites filled by a hybrid nanofiller with SRGO:SCNT of 3:1 showed the maximum IR-actuated stress recovery of lifting a 107.6 g weight up 4.7 cm in 18 s. The stress recovery delivered a high energy density of 0.63 J/g and shape recovery force up to 1.2 MPa due to high thermal conductivity (1.473 W/mK) and Young's modulus of 23.4 MPa. Results indicate that a trade-off between the stiffness and efficient heat transfer controlled by synergistic effect between SRGO and SCNT is critical for high mechanical power output of IR-triggered actuators. IR-actuated shape recovery of SRGO/SCNT/TPU nanocomposites combining high energy density and output forces can be further developed for advanced optomechanical systems.

  1. Event-triggered attitude control of spacecraft

    NASA Astrophysics Data System (ADS)

    Wu, Baolin; Shen, Qiang; Cao, Xibin

    2018-02-01

    The problem of spacecraft attitude stabilization control system with limited communication and external disturbances is investigated based on an event-triggered control scheme. In the proposed scheme, information of attitude and control torque only need to be transmitted at some discrete triggered times when a defined measurement error exceeds a state-dependent threshold. The proposed control scheme not only guarantees that spacecraft attitude control errors converge toward a small invariant set containing the origin, but also ensures that there is no accumulation of triggering instants. The performance of the proposed control scheme is demonstrated through numerical simulation.

  2. Dissociable brain mechanisms underlying the conscious and unconscious control of behavior.

    PubMed

    van Gaal, Simon; Lamme, Victor A F; Fahrenfort, Johannes J; Ridderinkhof, K Richard

    2011-01-01

    Cognitive control allows humans to overrule and inhibit habitual responses to optimize performance in challenging situations. Contradicting traditional views, recent studies suggest that cognitive control processes can be initiated unconsciously. To further capture the relation between consciousness and cognitive control, we studied the dynamics of inhibitory control processes when triggered consciously versus unconsciously in a modified version of the stop task. Attempts to inhibit an imminent response were often successful after unmasked (visible) stop signals. Masked (invisible) stop signals rarely succeeded in instigating overt inhibition but did trigger slowing down of response times. Masked stop signals elicited a sequence of distinct ERP components that were also observed on unmasked stop signals. The N2 component correlated with the efficiency of inhibitory control when elicited by unmasked stop signals and with the magnitude of slowdown when elicited by masked stop signals. Thus, the N2 likely reflects the initiation of inhibitory control, irrespective of conscious awareness. The P3 component was much reduced in amplitude and duration on masked versus unmasked stop trials. These patterns of differences and similarities between conscious and unconscious cognitive control processes are discussed in a framework that differentiates between feedforward and feedback connections in yielding conscious experience.

  3. Micro-to-nano-scale deformation mechanisms of a bimodal ultrafine eutectic composite

    PubMed Central

    Lee, Seoung Wan; Kim, Jeong Tae; Hong, Sung Hwan; Park, Hae Jin; Park, Jun-Young; Lee, Nae Sung; Seo, Yongho; Suh, Jin Yoo; Eckert, Jürgen; Kim, Do Hyang; Park, Jin Man; Kim, Ki Buem

    2014-01-01

    The outstading mechanical properties of bimodal ultrafine eutectic composites (BUECs) containing length scale hierarchy in eutectic structure were demonstrated by using AFM observation of surface topography with quantitative height measurements and were interpreted in light of the details of the deformation mechanisms by three different interface modes. It is possible to develop a novel strain accommodated eutectic structure for triggering three different interface-controlled deformation modes; (I) rotational boundary mode, (II) accumulated interface mode and (III) individual interface mode. A strain accommodated microstructure characterized by the surface topology gives a hint to design a novel ultrafine eutectic alloys with excellent mechanical properties. PMID:25265897

  4. Event-triggered decentralized adaptive fault-tolerant control of uncertain interconnected nonlinear systems with actuator failures.

    PubMed

    Choi, Yun Ho; Yoo, Sung Jin

    2018-06-01

    This paper investigates the event-triggered decentralized adaptive tracking problem of a class of uncertain interconnected nonlinear systems with unexpected actuator failures. It is assumed that local control signals are transmitted to local actuators with time-varying faults whenever predefined conditions for triggering events are satisfied. Compared with the existing control-input-based event-triggering strategy for adaptive control of uncertain nonlinear systems, the aim of this paper is to propose a tracking-error-based event-triggering strategy in the decentralized adaptive fault-tolerant tracking framework. The proposed approach can relax drastic changes in control inputs caused by actuator faults in the existing triggering strategy. The stability of the proposed event-triggering control system is analyzed in the Lyapunov sense. Finally, simulation comparisons of the proposed and existing approaches are provided to show the effectiveness of the proposed theoretical result in the presence of actuator faults. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

  5. Is gluten a cause of gastrointestinal symptoms in people without celiac disease?

    PubMed

    Biesiekierski, Jessica R; Muir, Jane G; Gibson, Peter R

    2013-12-01

    The avoidance of wheat- and gluten-containing products is a worldwide phenomenon. While celiac disease is a well-established entity, the evidence base for gluten as a trigger of symptoms in patients without celiac disease (so-called 'non-celiac gluten sensitivity' or NCGS) is limited. The problems lie in the complexity of wheat and the ability of its carbohydrate as well as protein components to trigger gastrointestinal symptoms, the potentially false assumption that response to a gluten-free diet equates to an effect of gluten withdrawal, and diagnostic criteria for coeliac disease. Recent randomized controlled re-challenge trials have suggested that gluten may worsen gastrointestinal symptoms, but failed to confirm patients with self-perceived NCGS have specific gluten sensitivity. Furthermore, mechanisms by which gluten triggers symptoms have yet to be identified. This review discusses the most recent scientific evidence and our current understanding of NCGS.

  6. Pathway diversity leads to 2D-nanostructure in photo-triggered supramolecular assembly.

    PubMed

    Ghosh, Suhrit; Pal, Deep Sankar

    2018-03-31

    This communication reports photo-triggered supramolecular assembly of a naphthalene-diimide (NDI) derivative, appended with a photo-labile ortho-nitrobenzyl (ONB)-ester protected carboxylic acid. Photo-irradiation produces the free COOH group which facilitates H-bonding driven face-to-face stacking of the NDI chromophores producing an ultra-thin (height < 2.0 nm) two-dimensional (2D) nano-sheet. In contrast, spontaneous supramolecular assembly of the same active monomer exhibits entirely different features such as uncontrolled growth, J-aggregation and fibrillar morphology. A completely different pathway for photo-triggered assembly is attributed to the dual function of the photo-caged pro-monomer in (i) producing the carboxylic acid in controlled manner and (ii) simultaneously inhibiting the spontaneous J-aggregation of the photo-generated monomers by ester-carboxylic acid H-bonding and in turn directing a distinct growth mechanism. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Photochemical mechanisms of light-triggered release from nanocarriers

    PubMed Central

    Fomina, Nadezda; Sankaranarayanan, Jagadis; Almutairi, Adah

    2012-01-01

    Over the last three decades, a handful of photochemical mechanisms have been applied to a large number of nanoscale assemblies that encapsulate a payload to afford spatio-temporal and remote control over activity of the encapsulated payload. Many of these systems are designed with an eye towards biomedical applications, as spatio-temporal and remote control of bioactivity would advance research and clinical practice. This review covers five underlying photochemical mechanisms that govern the activity of the majority of photoresponsive nanocarriers: 1. photo driven isomerization and oxidation, 2. surface plasmon absorption and photothermal effects, 3. photo driven hydrophobicity changes, 4. photo driven polymer backbone fragmentation and 5. photo driven de-crosslinking. The ways in which these mechanisms have been incorporated into nanocarriers and how they affect release is detailed, as well as the advantages and disadvantages of each system. PMID:22386560

  8. Transcutaneous vagus nerve stimulation (tVNS) enhances conflict-triggered adjustment of cognitive control.

    PubMed

    Fischer, Rico; Ventura-Bort, Carlos; Hamm, Alfons; Weymar, Mathias

    2018-04-24

    Response conflicts play a prominent role in the flexible adaptation of behavior as they represent context-signals that indicate the necessity for the recruitment of cognitive control. Previous studies have highlighted the functional roles of the affectively aversive and arousing quality of the conflict signal in triggering the adaptation process. To further test this potential link with arousal, participants performed a response conflict task in two separate sessions with either transcutaneous vagus nerve stimulation (tVNS), which is assumed to activate the locus coeruleus-noradrenaline (LC-NE) system, or with neutral sham stimulation. In both sessions the N2 and P3 event-related potentials (ERP) were assessed. In line with previous findings, conflict interference, the N2 and P3 amplitude were reduced after conflict. Most importantly, this adaptation to conflict was enhanced under tVNS compared to sham stimulation for conflict interference and the N2 amplitude. No effect of tVNS on the P3 component was found. These findings suggest that tVNS increases behavioral and electrophysiological markers of adaptation to conflict. Results are discussed in the context of the potentially underlying LC-NE and other neuromodulatory (e.g., GABA) systems. The present findings add important pieces to the understanding of the neurophysiological mechanisms of conflict-triggered adjustment of cognitive control.

  9. Laboratory investigations of earthquake dynamics

    NASA Astrophysics Data System (ADS)

    Xia, Kaiwen

    In this thesis this will be attempted through controlled laboratory experiments that are designed to mimic natural earthquake scenarios. The earthquake dynamic rupturing process itself is a complicated phenomenon, involving dynamic friction, wave propagation, and heat production. Because controlled experiments can produce results without assumptions needed in theoretical and numerical analysis, the experimental method is thus advantageous over theoretical and numerical methods. Our laboratory fault is composed of carefully cut photoelastic polymer plates (Homahte-100, Polycarbonate) held together by uniaxial compression. As a unique unit of the experimental design, a controlled exploding wire technique provides the triggering mechanism of laboratory earthquakes. Three important components of real earthquakes (i.e., pre-existing fault, tectonic loading, and triggering mechanism) correspond to and are simulated by frictional contact, uniaxial compression, and the exploding wire technique. Dynamic rupturing processes are visualized using the photoelastic method and are recorded via a high-speed camera. Our experimental methodology, which is full-field, in situ, and non-intrusive, has better control and diagnostic capacity compared to other existing experimental methods. Using this experimental approach, we have investigated several problems: dynamics of earthquake faulting occurring along homogeneous faults separating identical materials, earthquake faulting along inhomogeneous faults separating materials with different wave speeds, and earthquake faulting along faults with a finite low wave speed fault core. We have observed supershear ruptures, subRayleigh to supershear rupture transition, crack-like to pulse-like rupture transition, self-healing (Heaton) pulse, and rupture directionality.

  10. Bioactive films of zein/magnetite magnetically stimuli-responsive for controlled drug release

    NASA Astrophysics Data System (ADS)

    Marín, Tíffany; Montoya, Paula; Arnache, Oscar; Pinal, Rodolfo; Calderón, Jorge

    2018-07-01

    The Zein films in two configurations with magnetite nanoparticles (zein/NPs) and magnetite-acetaminophen (zein/NPs/Drug) were used as magnetically stimuli-responsive systems to propose a model of controlled release by dissolution and diffusion mechanism. Composite material films of zein/NPs and zein/NPs/Drug were made by dispersion of magnetite nanoparticles into zein solution then solvent casting of the solution on a flat Teflon substrate. The properties of composite films were analyzed by magnetization curves of (MvsH) and measurements of magnetic force microscopy (MFM). Drug release from the zein/NPs/Drug composite films was determined using a type II dissolution apparatus for a period of 2 h under applied magnetic field conditions. In addition, the diffusion mechanism was tested with zein/NPs films into diffusion cell containing acetaminophen solution for 24 h and using a permanent magnet as a remote trigger device. The results showed that the magnetite nanoparticles contained in the zein/NPs and zein/NPs/Drug composite films are stable, i.e., they do not undergo sufficiently high levels of oxidation as to alter their magnetic properties. Furthermore, the dissolution and diffusion results lead us to conclude that zein composite films effectively behave as stimuli-responsive systems triggered by an external magnetic field applied. The result is a model controlled release system whereby drug release can be controlled by adjusting the magnitude of the applied magnetic field.

  11. Elevated ATF4 Expression, in the Absence of Other Signals, Is Sufficient for Transcriptional Induction via CCAAT Enhancer-binding Protein-activating Transcription Factor Response Elements*

    PubMed Central

    Shan, Jixiu; Örd, Daima; Örd, Tõnis; Kilberg, Michael S.

    2009-01-01

    Protein limitation in vivo or amino acid deprivation of cells in culture causes a signal transduction cascade consisting of activation of the kinase GCN2 (general control nonderepressible 2), phosphorylation of eukaryotic initiation factor 2, and increased synthesis of activating transcription factor (ATF) 4 by a translational control mechanism. In a self-limiting transcriptional program, ATF4 transiently activates a wide range of downstream target genes involved in transport, cellular metabolism, and other cell functions. Simultaneous activation of other signal transduction pathways by amino acid deprivation led to the question of whether or not the increased abundance of ATF4 alone was sufficient to trigger the transcriptional control mechanisms. Using 293 cells that ectopically express ATF4 in a tetracycline-inducible manner showed that ATF4 target genes were activated in the absence of amino acid deprivation. Ectopic expression of ATF4 alone resulted in effective recruitment of the general transcription machinery, but some reduction in histone modification was observed. These data document that ATF4 alone is sufficient to trigger the amino acid-responsive transcriptional control program. However, the absolute amount of ectopic ATF4 required to achieve the same degree of transcriptional activation observed after amino acid limitation was greater, suggesting that other factors may serve to enhance ATF4 function. PMID:19509279

  12. LSTM, GRU, Highway and a Bit of Attention: An Empirical Overview for Language Modeling in Speech Recognition

    DTIC Science & Technology

    2016-09-12

    on learning word triggers with an attention mechanism. 5.1. Model descriptions 5.1.1. Attention layer A minimalistic attention mechanism can be...word trigger model based on a minimalistic attention mechanism: it already showed some interesting qualitative re- sults, while the performance was not

  13. Adaptive Event-Triggered Control Based on Heuristic Dynamic Programming for Nonlinear Discrete-Time Systems.

    PubMed

    Dong, Lu; Zhong, Xiangnan; Sun, Changyin; He, Haibo

    2017-07-01

    This paper presents the design of a novel adaptive event-triggered control method based on the heuristic dynamic programming (HDP) technique for nonlinear discrete-time systems with unknown system dynamics. In the proposed method, the control law is only updated when the event-triggered condition is violated. Compared with the periodic updates in the traditional adaptive dynamic programming (ADP) control, the proposed method can reduce the computation and transmission cost. An actor-critic framework is used to learn the optimal event-triggered control law and the value function. Furthermore, a model network is designed to estimate the system state vector. The main contribution of this paper is to design a new trigger threshold for discrete-time systems. A detailed Lyapunov stability analysis shows that our proposed event-triggered controller can asymptotically stabilize the discrete-time systems. Finally, we test our method on two different discrete-time systems, and the simulation results are included.

  14. Specific features of the control systems of new-modification 310-330-MW steam turbines manufactured by PAO turboatom

    NASA Astrophysics Data System (ADS)

    Shvetsov, V. L.; Babaev, I. N.

    2017-07-01

    Principal engineering solutions taken by PAO Turboatom when developing the control systems of the 310-325-MW turbines for thermal power stations are set forth. A schematic diagram of the control system is presented and the designs of the retrofitted basic mechanisms, viz., high-pressure steam-distribution unit and the cutoff valve, are described. It is noted that the accepted principles of designing the control systems allow retaining the following advantages of the latter: use of the condensate as a cheap nonflammable working fluid, valveless switches to control the locking servomotors, a mechanical ring-type turbine trip mechanism (TTM) in combination with an actuator fitted with two double-seated actuator valves to control the pressure in the pulse security lines, and a rotary valve to block the triggering of the actuator valves during successive testing of the TTM rings by filling the oil during the operation of the turbine and the subsequent raising of the above valves. The control systems of the new-modification turbines are based on microprocessor hardware using electromechanical converters to drive every cutoff valve as a universal solution that is not oriented towards a particular manufacturer of the control system electronics. Application of a mechanical turbine trip mechanism is acknowledged as indispensable for unconditional guarantee of the safe operation of the turbines irrespective of the presence of the electronic turbine trip mechanism.

  15. Numerical investigation of the triggering mechanisms of the Piz Dora sackung system (Val Mustair, Switzerland)

    NASA Astrophysics Data System (ADS)

    Riva, Federico; Agliardi, Federico; Crosta, Giovanni B.; Zanchi, Andrea

    2015-04-01

    Deep-Seated Gravitational Slope Deformations (DSGSD) are widespread phenomena in alpine environments, where they affect entire high-relief valley flanks involving huge rock volumes. Slope scale inherited structures related to ductile and brittle tectonic deformation can control the onset and development of DSGSD and the localization of strain in deep gravitational shear zones. Slope unloading, rock mass damage and hydrological perturbations related to deglaciation are considered important triggers of these phenomena in formerly glaciated areas. Furthermore, earthquake shaking and the long-term effects of seismicity in active tectonic areas might provide an additional triggering component. Nevertheless, the role played by these different processes and their interplay is not obvious, especially in geological context less typically favourable to DSGSD and in low-magnitude seismicity settings as the axial European Alps. We analysed the Piz Dora sackung system (Val Mustair, Switzerland), which affects conglomerates, meta-conglomerates and phyllites of the Austroalpine S-Charl nappe, involved in a slope-scale, WNW trending closed anticline fold. The area is actively uplifting, seismically active (maximum Mw>5) and experienced extensive glaciation during the LGM. The slope is affected by sharp gravitational morphostructures associated to the deep-seated sliding of 1.85 km3 of rock along a basal shear zone up to 300 m deep (Agliardi et al., 2014; Barbarano et al., 2015). We investigated the controlling role of inherited tectonic features and the relative influence of different candidate triggering processes (post-glacial debuttressing, related changes in slope hydrology, seismicity) through a series of 2D Distinct Element (DEM) numerical models set up using the code UDEC (ItascaTM). Based on field structural and geomechanical data, we discretized the slope into an ensemble of discontinuum domains, accounting for the slope-scale folded structure and characterised by unique combinations of rock mass properties and persistent brittle structural patterns related to folding or regional stress fields. We analysed the processes leading to DSGSD onset and evolution by testing combinations of: a) rock mass constitutive models; b) in situ stress fields; c) hydro-mechanical coupling; d) dynamic loadings. DEM results, validated using field evidence and discussed against the results of continuum-based Finite-Element models (Agliardi et al., 2014; Barbarano et al., 2015), suggest that DSGSD failure mechanisms are constrained by fold-related brittle structures, and stress and hydrologic conditioning of deglaciation were key triggers modulated by active tectonic processes. References: - Agliardi F., Barbarano M., Crosta G.B., Riva F. & Zanchi A. (2014). Inherited and active tectonic controls on the Piz Dora sackung system (Val Mustair). In 3rd Slope Tectonic Conference proceedings, NGU Report 2014.030. - Barbarano M., Agliardi F., Crosta G. B., & Zanchi A. (2015). Inherited and Active Tectonic Controls on the Piz Dora DSGSD (Val Müstair, Switzerland). In Engineering Geology for Society and Territory-Volume 2 (pp. 605-608). Springer International Publishing.

  16. Central FPGA-based destination and load control in the LHCb MHz event readout

    NASA Astrophysics Data System (ADS)

    Jacobsson, R.

    2012-10-01

    The readout strategy of the LHCb experiment is based on complete event readout at 1 MHz. A set of 320 sub-detector readout boards transmit event fragments at total rate of 24.6 MHz at a bandwidth usage of up to 70 GB/s over a commercial switching network based on Gigabit Ethernet to a distributed event building and high-level trigger processing farm with 1470 individual multi-core computer nodes. In the original specifications, the readout was based on a pure push protocol. This paper describes the proposal, implementation, and experience of a non-conventional mixture of a push and a pull protocol, akin to credit-based flow control. An FPGA-based central master module, partly operating at the LHC bunch clock frequency of 40.08 MHz and partly at a double clock speed, is in charge of the entire trigger and readout control from the front-end electronics up to the high-level trigger farm. One FPGA is dedicated to controlling the event fragment packing in the readout boards, the assignment of the farm node destination for each event, and controls the farm load based on an asynchronous pull mechanism from each farm node. This dynamic readout scheme relies on generic event requests and the concept of node credit allowing load control and trigger rate regulation as a function of the global farm load. It also allows the vital task of fast central monitoring and automatic recovery in-flight of failing nodes while maintaining dead-time and event loss at a minimum. This paper demonstrates the strength and suitability of implementing this real-time task for a very large distributed system in an FPGA where no random delays are introduced, and where extreme reliability and accurate event accounting are fundamental requirements. It was in use during the entire commissioning phase of LHCb and has been in faultless operation during the first two years of physics luminosity data taking.

  17. Stereotyped responses of Drosophila peptidergic neuronal ensemble depend on downstream neuromodulators

    PubMed Central

    Mena, Wilson; Diegelmann, Sören; Wegener, Christian; Ewer, John

    2016-01-01

    Neuropeptides play a key role in the regulation of behaviors and physiological responses including alertness, social recognition, and hunger, yet, their mechanism of action is poorly understood. Here, we focus on the endocrine control ecdysis behavior, which is used by arthropods to shed their cuticle at the end of every molt. Ecdysis is triggered by ETH (Ecdysis triggering hormone), and we show that the response of peptidergic neurons that produce CCAP (crustacean cardioactive peptide), which are key targets of ETH and control the onset of ecdysis behavior, depends fundamentally on the actions of neuropeptides produced by other direct targets of ETH and released in a broad paracrine manner within the CNS; by autocrine influences from the CCAP neurons themselves; and by inhibitory actions mediated by GABA. Our findings provide insights into how this critical insect behavior is controlled and general principles for understanding how neuropeptides organize neuronal activity and behaviors. DOI: http://dx.doi.org/10.7554/eLife.19686.001 PMID:27976997

  18. Environmentally Friendly Coating Technology for Autonomous Corrosion Control

    NASA Technical Reports Server (NTRS)

    Calle, Luz M.; Li, Wenyan; Buhrow, Jerry W.; Johnsey, Marissa N.; Jolley, Scott T.; Pearman, Benjamin P.; Zhang, Xuejun; Fitzpatrick, Lilliana; Gillis, Mathew; Blanton, Michael; hide

    2016-01-01

    This work concerns the development of environmentally friendly encapsulation technology, specifically designed to incorporate corrosion indicators, inhibitors, and self-healing agents into a coating, in such a way that the delivery of the indicators and inhibitors is triggered by the corrosion process, and the delivery of self-healing agents is triggered by mechanical damage to the coating. Encapsulation of the active corrosion control ingredients allows the incorporation of desired autonomous corrosion control functions such as: early corrosion detection, hidden corrosion detection, corrosion inhibition, and self-healing of mechanical damage into a coating. The technology offers the versatility needed to include one or several corrosion control functions into the same coating.The development of the encapsulation technology has progressed from the initial proof-of-concept work, in which a corrosion indicator was encapsulated into an oil-core (hydrophobic) microcapsule and shown to be delivered autonomously, under simulated corrosion conditions, to a sophisticated portfolio of micro carriers (organic, inorganic, and hybrid) that can be used to deliver a wide range of active corrosion ingredients at a rate that can be adjusted to offer immediate as well as long-term corrosion control. The micro carriers have been incorporated into different coating formulas to test and optimize the autonomous corrosion detection, inhibition, and self-healing functions of the coatings. This paper provides an overview of progress made to date and highlights recent technical developments, such as improved corrosion detection sensitivity, inhibitor test results in various types of coatings, and highly effective self-healing coatings based on green chemistry.

  19. Improving the Efficacy of Anticancer Drugs via Encapsulation and Acoustic Release.

    PubMed

    Ahmed, Salma E; Awad, Nahid; Paul, Vinod; Moussa, Hesham G; Husseini, Ghaleb A

    2018-06-08

    Conventional chemotherapeutics lack the specificity and controllability, thus may poison healthy cells while attempting to kill cancerous ones. Newly developed nano-drug delivery systems have shown promise in delivering anti-tumor agents with enhanced stability, durability and overall performance; especially when used along with targeting and triggering techniques. This work traces back the history of chemotherapy, addressing the main challenges that have encouraged the medical researchers to seek a sanctuary in nanotechnological-based drug delivery systems that are grafted with appropriate targeting techniques and drug release mechanisms. A special focus will be paid towards acoustically triggered liposomes encapsulating doxorubicin. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Leaf shedding as an anti-bacterial defense in Arabidopsis cauline leaves

    PubMed Central

    2017-01-01

    Plants utilize an innate immune system to protect themselves from disease. While many molecular components of plant innate immunity resemble the innate immunity of animals, plants also have evolved a number of truly unique defense mechanisms, particularly at the physiological level. Plant’s flexible developmental program allows them the unique ability to simply produce new organs as needed, affording them the ability to replace damaged organs. Here we develop a system to study pathogen-triggered leaf abscission in Arabidopsis. Cauline leaves infected with the bacterial pathogen Pseudomonas syringae abscise as part of the defense mechanism. Pseudomonas syringae lacking a functional type III secretion system fail to elicit an abscission response, suggesting that the abscission response is a novel form of immunity triggered by effectors. HAESA/HAESA-like 2, INFLORESCENCE DEFICIENT IN ABSCISSION, and NEVERSHED are all required for pathogen-triggered abscission to occur. Additionally phytoalexin deficient 4, enhanced disease susceptibility 1, salicylic acid induction-deficient 2, and senescence-associated gene 101 plants with mutations in genes necessary for bacterial defense and salicylic acid signaling, and NahG transgenic plants with low levels of salicylic acid fail to abscise cauline leaves normally. Bacteria that physically contact abscission zones trigger a strong abscission response; however, long-distance signals are also sent from distal infected tissue to the abscission zone, alerting the abscission zone of looming danger. We propose a threshold model regulating cauline leaf defense where minor infections are handled by limiting bacterial growth, but when an infection is deemed out of control, cauline leaves are shed. Together with previous results, our findings suggest that salicylic acid may regulate both pathogen- and drought-triggered leaf abscission. PMID:29253890

  1. Light-Adaptive Supramolecular Nacre-Mimetic Nanocomposites.

    PubMed

    Zhu, Baolei; Noack, Manuel; Merindol, Remi; Barner-Kowollik, Christopher; Walther, Andreas

    2016-08-10

    Nature provides design paradigms for adaptive, self-healing, and synergistic high-performance structural materials. Nacre's brick-and-mortar architecture is renowned for combining stiffness, toughness, strength, and lightweightness. Although elaborate approaches exist to mimic its static structure and performance, and to incorporate functionalities for the engineering world, there is a profound gap in addressing adaptable mechanical properties, particularly using remote, quick, and spatiotemporal triggers. Here, we demonstrate a generic approach to control the mechanical properties of nacre-inspired nanocomposites by designing a photothermal energy cascade using colloidal graphene as light-harvesting unit and coupling it to molecularly designed, thermoreversible, supramolecular bonds in the nanoconfined soft phase of polymer/nanoclay nacre-mimetics. The light intensity leads to adaptive steady-states balancing energy uptake and dissipation. It programs the mechanical properties and switches the materials from high stiffness/strength to higher toughness within seconds under spatiotemporal control. We envisage possibilities beyond mechanical materials, for example, light-controlled (re)shaping or actuation in highly reinforced nanocomposites.

  2. Mechanofluorochromic Carbon Nanodots: Controllable Pressure-Triggered Blue- and Red-Shifted Photoluminescence.

    PubMed

    Liu, Cui; Xiao, Guanjun; Yang, Mengli; Zou, Bo; Zhang, Zhi-Ling; Pang, Dai-Wen

    2018-02-12

    Mechanofluorochromic materials, which change their photoluminescence (PL) colors in responding to mechanical stimuli, can be used as mechanosensors, security papers, and photoelectronic devices. However, traditional mechanofluorochromic materials can only be adjusted to a monotone direction upon the external stimuli. Controllable pressure-triggered blue- and red-shifted PL is reported for C-dots. The origin of mechanofluorochromism (MFC) in C-dots is interpreted based on structure-property relationships. The carbonyl group and the π-conjugated system play key roles in the PL change of C-dots under high pressure. As the pressure increases, the enhanced π-π stacking of the π-conjugated system causes the red-shift of PL, while the conversion of carbonyl groups eventually induces a blue-shift. Together with their low toxicity, good hydrophilicity, and small size, the tunable MFC property would boost various potential applications of C-dots. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Microfluidic mixing triggered by an external LED illumination.

    PubMed

    Venancio-Marques, Anna; Barbaud, Fanny; Baigl, Damien

    2013-02-27

    The mixing of confined liquids is a central yet challenging operation in miniaturized devices. Microfluidic mixing is usually achieved with passive mixers that are robust but poorly flexible, or active mixers that offer dynamic control but mainly rely on electrical or mechanical transducers, which increase the fragility, cost, and complexity of the device. Here, we describe the first remote and reversible control of microfluidic mixing triggered by a light illumination simply provided by an external LED illumination device. The approach is based on the light-induced generation of water microdroplets acting as reversible stirrers of two continuous oil phase flows containing samples to be mixed. We demonstrate many cycles of reversible photoinduced transitions between a nonmixing behavior and full homogenization of the two oil phases. The method is cheap, portable, and adaptable to many device configurations, thus constituting an essential brick for the generation of future all-optofluidic chip.

  4. Recent Developments on Autonomous Corrosion Protection Through Encapsulation

    NASA Technical Reports Server (NTRS)

    Li, W.; Buhrow, J. W.; Calle, L. M.; Gillis, M.; Blanton, M.; Hanna, J.; Rawlins, J.

    2015-01-01

    This paper concerns recent progress in the development of a multifunctional smart coating, based on microencapsulation, for the autonomous detection and control of corrosion. Microencapsulation has been validated and optimized to incorporate desired corrosion control functionalities, such as early corrosion detection and inhibition, through corrosion-initiated release of corrosion indicators and inhibitors, as well as self-healing agent release triggered by mechanical damage. While proof-of-concept results have been previously reported, more recent research and development efforts have concentrated on improving coating compatibility and synthesis procedure scalability, with a targeted goal of obtaining easily dispersible pigment-grade type microencapsulated materials. The recent progress has resulted in the development of pH-sensitive microparticles as a corrosion-triggered delivery system for corrosion indicators and inhibitors. The synthesis and early corrosion indication results obtained with coating formulations that incorporate these microparticles are reported. The early corrosion indicating results were obtained with color changing and with fluorescent indicators.

  5. A dual-mode disturbance-accommodating controller for the Hubble Space Telescope

    NASA Astrophysics Data System (ADS)

    Addington, Stewart; Johnson, C. D.

    Cyclic thermal expansions and mechanical stiction effects in the Solar Arrays on the Hubble Space Telescope (HST) are triggering repeated occurrences of damped, relaxation-type flex-body vibrations of the solar arrays. Those solar array vibrations are, in turn, causing unwanted, oscillating disturbance torques on the HST main body, which cause unwanted deviations of the telescope from its specified pointing direction. In this paper we propose two strategies one can adopt in designing a telescope-pointing controller to cope with the aforementioned disturbances: (1) a `total isolation' (TI) control strategy whereby the HST controller torques are designed to adaptively counteract and cancel-out the persistent disturbing torques that are causing the unwanted telescope motions, and (2) an `array damping' (AD) control strategy whereby the HST controller torques are used to actively augment the natural dampening of the solar array vibrations and the attendant telescope motions, between triggerings of the stiction-related flex-body relaxation oscillations. Using the principles of Disturbance-Accommodating Control (DAC) Theory a dual-mode controller for a generic, planar-motion (single-axis) model of the HST is proposed. This controller incorporates both the TI and AD modes of disturbance-accommodation. Simulation studies of the closed-loop system using generic parameter values clearly indicate, qualitatively, the enhanced pointing-performance such a controller can achieve.

  6. Triggering Mechanism for Neutron Induced Single-Event Burnout in Power Devices

    NASA Astrophysics Data System (ADS)

    Shoji, Tomoyuki; Nishida, Shuichi; Hamada, Kimimori

    2013-04-01

    Cosmic ray neutrons can trigger catastrophic failures in power devices. It has been reported that parasitic transistor action causes single-event burnout (SEB) in power metal-oxide-semiconductor field-effect transistors (MOSFETs) and insulated gate bipolar transistors (IGBTs). However, power diodes do not have an inherent parasitic transistor. In this paper, we describe the mechanism triggering SEB in power diodes for the first time using transient device simulation. Initially, generated electron-hole pairs created by incident recoil ions generate transient current, which increases the electron density in the vicinity of the n-/n+ boundary. The space charge effect of the carriers leads to an increase in the strength of the electric field at the n-/n+ boundary. Finally, the onset of impact ionization at the n-/n+ boundary can trigger SEB. Furthermore, this failure is closely related to diode secondary breakdown. It was clarified that the impact ionization at the n-/n+ boundary is a key point of the mechanism triggering SEB in power devices.

  7. Mechanisms of Intentional Binding and Sensory Attenuation: The Role of Temporal Prediction, Temporal Control, Identity Prediction, and Motor Prediction

    ERIC Educational Resources Information Center

    Hughes, Gethin; Desantis, Andrea; Waszak, Florian

    2013-01-01

    Sensory processing of action effects has been shown to differ from that of externally triggered stimuli, with respect both to the perceived timing of their occurrence (intentional binding) and to their intensity (sensory attenuation). These phenomena are normally attributed to forward action models, such that when action prediction is consistent…

  8. Polycystin-1 is a Cardiomyocyte Mechanosensor That Governs L-type Ca2+ Channel Protein Stability

    PubMed Central

    Pedrozo, Zully; Criollo, Alfredo; Battiprolu, Pavan K.; Morales, Cyndi R.; Contreras, Ariel; Fernández, Carolina; Jiang, Nan; Luo, Xiang; Caplan, Michael J.; Somlo, Stefan; Rothermel, Beverly A.; Gillette, Thomas G.; Lavandero, Sergio; Hill, Joseph A.

    2015-01-01

    Background L-type calcium channel (LTCC) activity is critical to afterload-induced hypertrophic growth of the heart. However, mechanisms governing mechanical stress-induced activation of LTCC activity are obscure. Polycystin-1 (PC-1) is a G-protein-coupled receptor-like protein that functions as a mechanosensor in a variety of cell types and is present in cardiomyocytes. Methods and Results We subjected neonatal rat ventricular myocytes (NRVMs) to mechanical stretch by exposing them to hypo-osmotic (HS) medium or cyclic mechanical stretch, triggering cell growth in a manner dependent on LTCC activity. RNAi-dependent knockdown of PC-1 blocked this hypertrophy. Over-expression of a C-terminal fragment of PC-1 was sufficient to trigger NRVM hypertrophy. Exposing NRVMs to HS medium resulted in an increase in α1C protein levels, a response that was prevented by PC-1 knockdown. MG132, a proteasomal inhibitor, rescued PC-1 knockdown-dependent declines in α1C protein. To test this in vivo, we engineered mice harboring conditional silencing of PC-1 selectively in cardiomyocytes (PC-1 KO) and subjected them to mechanical stress in vivo (transverse aortic constriction, TAC). At baseline, PC-1 KO mice manifested decreased cardiac function relative to littermate controls, and α1C LTCC protein levels were significantly lower in PC-1 KO hearts. Whereas control mice manifested robust TAC-induced increases in cardiac mass, PC-1 KO mice showed no significant growth. Likewise, TAC-elicited increases in hypertrophic markers and interstitial fibrosis were blunted in the knockout animals Conclusions PC-1 is a cardiomyocyte mechanosensor and is required for cardiac hypertrophy through a mechanism that involves stabilization of α1C protein. PMID:25888683

  9. Polycystin-1 Is a Cardiomyocyte Mechanosensor That Governs L-Type Ca2+ Channel Protein Stability.

    PubMed

    Pedrozo, Zully; Criollo, Alfredo; Battiprolu, Pavan K; Morales, Cyndi R; Contreras-Ferrat, Ariel; Fernández, Carolina; Jiang, Nan; Luo, Xiang; Caplan, Michael J; Somlo, Stefan; Rothermel, Beverly A; Gillette, Thomas G; Lavandero, Sergio; Hill, Joseph A

    2015-06-16

    L-type calcium channel activity is critical to afterload-induced hypertrophic growth of the heart. However, the mechanisms governing mechanical stress-induced activation of L-type calcium channel activity are obscure. Polycystin-1 (PC-1) is a G protein-coupled receptor-like protein that functions as a mechanosensor in a variety of cell types and is present in cardiomyocytes. We subjected neonatal rat ventricular myocytes to mechanical stretch by exposing them to hypo-osmotic medium or cyclic mechanical stretch, triggering cell growth in a manner dependent on L-type calcium channel activity. RNAi-dependent knockdown of PC-1 blocked this hypertrophy. Overexpression of a C-terminal fragment of PC-1 was sufficient to trigger neonatal rat ventricular myocyte hypertrophy. Exposing neonatal rat ventricular myocytes to hypo-osmotic medium resulted in an increase in α1C protein levels, a response that was prevented by PC-1 knockdown. MG132, a proteasomal inhibitor, rescued PC-1 knockdown-dependent declines in α1C protein. To test this in vivo, we engineered mice harboring conditional silencing of PC-1 selectively in cardiomyocytes (PC-1 knockout) and subjected them to mechanical stress in vivo (transverse aortic constriction). At baseline, PC-1 knockout mice manifested decreased cardiac function relative to littermate controls, and α1C L-type calcium channel protein levels were significantly lower in PC-1 knockout hearts. Whereas control mice manifested robust transverse aortic constriction-induced increases in cardiac mass, PC-1 knockout mice showed no significant growth. Likewise, transverse aortic constriction-elicited increases in hypertrophic markers and interstitial fibrosis were blunted in the knockout animals PC-1 is a cardiomyocyte mechanosensor that is required for cardiac hypertrophy through a mechanism that involves stabilization of α1C protein. © 2015 American Heart Association, Inc.

  10. The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs

    PubMed Central

    Garzia, Aitor; Jafarnejad, Seyed Mehdi; Meyer, Cindy; Chapat, Clément; Gogakos, Tasos; Morozov, Pavel; Amiri, Mehdi; Shapiro, Maayan; Molina, Henrik; Tuschl, Thomas; Sonenberg, Nahum

    2017-01-01

    Cryptic polyadenylation within coding sequences (CDS) triggers ribosome-associated quality control (RQC), followed by degradation of the aberrant mRNA and polypeptide, ribosome disassembly and recycling. Although ribosomal subunit dissociation and nascent peptide degradation are well-understood, the molecular sensors of aberrant mRNAs and their mechanism of action remain unknown. We studied the Zinc Finger Protein 598 (ZNF598) using PAR-CLIP and revealed that it cross-links to tRNAs, mRNAs and rRNAs, thereby placing the protein on translating ribosomes. Cross-linked reads originating from AAA-decoding tRNALys(UUU) were 10-fold enriched over its cellular abundance, and poly-lysine encoded by poly(AAA) induced RQC in a ZNF598-dependent manner. Encounter with translated polyA segments by ZNF598 triggered ubiquitination of several ribosomal proteins, requiring the E2 ubiquitin ligase UBE2D3 to initiate RQC. Considering that human CDS are devoid of >4 consecutive AAA codons, sensing of prematurely placed polyA tails by a specialized RNA-binding protein is a novel nucleic-acid-based surveillance mechanism of RQC. PMID:28685749

  11. The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs.

    PubMed

    Garzia, Aitor; Jafarnejad, Seyed Mehdi; Meyer, Cindy; Chapat, Clément; Gogakos, Tasos; Morozov, Pavel; Amiri, Mehdi; Shapiro, Maayan; Molina, Henrik; Tuschl, Thomas; Sonenberg, Nahum

    2017-07-07

    Cryptic polyadenylation within coding sequences (CDS) triggers ribosome-associated quality control (RQC), followed by degradation of the aberrant mRNA and polypeptide, ribosome disassembly and recycling. Although ribosomal subunit dissociation and nascent peptide degradation are well-understood, the molecular sensors of aberrant mRNAs and their mechanism of action remain unknown. We studied the Zinc Finger Protein 598 (ZNF598) using PAR-CLIP and revealed that it cross-links to tRNAs, mRNAs and rRNAs, thereby placing the protein on translating ribosomes. Cross-linked reads originating from AAA-decoding tRNA Lys (UUU) were 10-fold enriched over its cellular abundance, and poly-lysine encoded by poly(AAA) induced RQC in a ZNF598-dependent manner. Encounter with translated polyA segments by ZNF598 triggered ubiquitination of several ribosomal proteins, requiring the E2 ubiquitin ligase UBE2D3 to initiate RQC. Considering that human CDS are devoid of >4 consecutive AAA codons, sensing of prematurely placed polyA tails by a specialized RNA-binding protein is a novel nucleic-acid-based surveillance mechanism of RQC.

  12. Nanocomposite thin films for triggerable drug delivery.

    PubMed

    Vannozzi, Lorenzo; Iacovacci, Veronica; Menciassi, Arianna; Ricotti, Leonardo

    2018-05-01

    Traditional drug release systems normally rely on a passive delivery of therapeutic compounds, which can be partially programmed, prior to injection or implantation, through variations in the material composition. With this strategy, the drug release kinetics cannot be remotely modified and thus adapted to changing therapeutic needs. To overcome this issue, drug delivery systems able to respond to external stimuli are highly desirable, as they allow a high level of temporal and spatial control over drug release kinetics, in an operator-dependent fashion. Areas covered: On-demand drug delivery systems actually represent a frontier in this field and are attracting an increasing interest at both research and industrial level. Stimuli-responsive thin films, enabled by nanofillers, hold a tremendous potential in the field of triggerable drug delivery systems. The inclusion of responsive elements in homogeneous or heterogeneous thin film-shaped polymeric matrices strengthens and/or adds intriguing properties to conventional (bare) materials in film shape. Expert opinion: This Expert Opinion review aims to discuss the approaches currently pursued to achieve an effective on-demand drug delivery, through nanocomposite thin films. Different triggering mechanisms allowing a fine control on drug delivery are described, together with current challenges and possible future applications in therapy and surgery.

  13. Triggered creep as a possible mechanism for delayed dynamic triggering of tremor and earthquakes

    USGS Publications Warehouse

    Shelly, David R.; Peng, Zhigang; Hill, David P.; Aiken, Chastity

    2011-01-01

    The passage of radiating seismic waves generates transient stresses in the Earth's crust that can trigger slip on faults far away from the original earthquake source. The triggered fault slip is detectable in the form of earthquakes and seismic tremor. However, the significance of these triggered events remains controversial, in part because they often occur with some delay, long after the triggering stress has passed. Here we scrutinize the location and timing of tremor on the San Andreas fault between 2001 and 2010 in relation to distant earthquakes. We observe tremor on the San Andreas fault that is initiated by passing seismic waves, yet migrates along the fault at a much slower velocity than the radiating seismic waves. We suggest that the migrating tremor records triggered slow slip of the San Andreas fault as a propagating creep event. We find that the triggered tremor and fault creep can be initiated by distant earthquakes as small as magnitude 5.4 and can persist for several days after the seismic waves have passed. Our observations of prolonged tremor activity provide a clear example of the delayed dynamic triggering of seismic events. Fault creep has been shown to trigger earthquakes, and we therefore suggest that the dynamic triggering of prolonged fault creep could provide a mechanism for the delayed triggering of earthquakes. ?? 2011 Macmillan Publishers Limited. All rights reserved.

  14. Edge Mechanisms for Power Excursion Control in Burning Plasmas

    NASA Astrophysics Data System (ADS)

    Hill, M. D.; Stacey, W. M.

    2017-10-01

    ITER must have active and preferably also passive control mechanisms that will limit inadvertent plasma power excursions which could trigger runaway fusion heating. We are identifying and investigating the potential of ion-orbit loss, impurity seeding, and various divertor ``choking'' phenomena to control or limit sudden increases in plasma density or temperature by reducing energy confinement, increasing radiation loss, etc., with the idea that such mechanisms could be tested on DIII-D and other existing tokamaks. We are assembling an edge-divertor code (GTEDGE-2) with a neutral transport model and a burn dynamics code, for this purpose. One potential control mechanism is the enhanced ion orbit loss from the thermalized ion distribution that would result from heating of the thermalized plasma ion distribution. Another possibility is impurity seeding with ions whose emissivity would increase sharply if the edge temperature increased. Enhanced radiative losses should also reduce the thermal energy flux across the separatrix, perhaps dropping the plasma into the poorer L-mode confinement regime. We will present some initial calculations to quantify these ideas. Work supported by US DOE under DE-FC02-04ER54698.

  15. Fusion of Enveloped Viruses in Endosomes

    PubMed Central

    White, Judith M.; Whittaker, Gary R.

    2016-01-01

    Ari Helenius launched the field of enveloped virus fusion in endosomes with a seminal paper in the Journal of Cell Biology in 1980. In the intervening years a great deal has been learned about the structures and mechanisms of viral membrane fusion proteins as well as about the endosomes in which different enveloped viruses fuse and the endosomal cues that trigger fusion. We now recognize three classes of viral membrane fusion proteins based on structural criteria and four mechanisms of fusion triggering. After reviewing general features of viral membrane fusion proteins and viral fusion in endosomes, we delve into three characterized mechanisms for viral fusion triggering in endosomes: by low pH, by receptor binding plus low pH, and by receptor binding plus the action of a protease. We end with a discussion of viruses that may employ novel endosomal fusion triggering mechanisms. A key take home message is that enveloped viruses that enter cells by fusing in endosomes traverse the endocytic pathway until they reach an endosome that has all of the environmental conditions (pH, proteases, ions, intracellular receptors, and lipid composition) to (if needed) prime and (in all cases) trigger the fusion protein and to support membrane fusion. PMID:26935856

  16. Emotional triggers in myocardial infarction: do they matter?

    PubMed

    Edmondson, Donald; Newman, Jonathan D; Whang, William; Davidson, Karina W

    2013-01-01

    Considerable excitement and interest have arisen recently concerning the role that acute emotional triggers may play in precipitating a myocardial infarction (MI). Observational studies have found repeatedly that patients report excessive anger, anxiety, sadness, grief, or acute stress immediately prior to onset of MI, and recent meta-analyses summarizing these findings reported strong associations between MI occurrence and many of these acute emotions. However, it is unclear whether and through what mechanisms acute emotional triggers might influence MI, and whether there is any clinical utility in knowing if or how emotions trigger MI. We debate whether emotional triggers matter by reviewing the recent evidence for the association between acute emotional triggers and MI and by describing the potential pathophysiological characteristics and mechanisms underlying this association and the preventive strategies that could be used to mitigate the risk of acute MI. We also examine whether the study of emotional triggers could influence clinical risk management or changes in clinical practice/management. We offer suggestions for research that might shed light on whether emotional triggers could initiate a paradigm shift in preventive cardiology, or whether acute emotional triggers are either intractable catalysts for, or merely an epiphenomenon of, some MIs.

  17. Emotional triggers in myocardial infarction: do they matter?

    PubMed Central

    Edmondson, Donald; Newman, Jonathan D.; Whang, William; Davidson, Karina W.

    2013-01-01

    Considerable excitement and interest have arisen recently concerning the role that acute emotional triggers may play in precipitating a myocardial infarction (MI). Observational studies have found repeatedly that patients report excessive anger, anxiety, sadness, grief, or acute stress immediately prior to onset of MI, and recent meta-analyses summarizing these findings reported strong associations between MI occurrence and many of these acute emotions. However, it is unclear whether and through what mechanisms acute emotional triggers might influence MI, and whether there is any clinical utility in knowing if or how emotions trigger MI. We debate whether emotional triggers matter by reviewing the recent evidence for the association between acute emotional triggers and MI and by describing the potential pathophysiological characteristics and mechanisms underlying this association and the preventive strategies that could be used to mitigate the risk of acute MI. We also examine whether the study of emotional triggers could influence clinical risk management or changes in clinical practice/management. We offer suggestions for research that might shed light on whether emotional triggers could initiate a paradigm shift in preventive cardiology, or whether acute emotional triggers are either intractable catalysts for, or merely an epiphenomenon of, some MIs. PMID:23178642

  18. Induced and triggered earthquakes at The Geysers geothermal reservoir

    NASA Astrophysics Data System (ADS)

    Johnson, Lane R.; Majer, Ernest L.

    2017-05-01

    The Geysers geothermal reservoir in northern California is the site of numerous studies of both seismicity induced by injection of fluids and seismicity triggered by other earthquakes. Data from a controlled experiment in the northwest part of The Geysers in the time period 2011 to 2015 are used to study these induced and triggered earthquakes and possible differences between them. Causal solutions to the elastic equations for a porous medium show how fluid injection generates fast elastic and diffusion waves followed by a much slower diffusive wake. Calculations of fluid increment, fluid pressure and elastic stress are used to investigate both when and why seismic failure takes place. Taking into account stress concentrations caused by material heterogeneity leads to the conclusion that fluid injection by itself can cause seismic activity with no need for tectonic forces. Induced events that occur at early times are best explained by changes in stress rate, while those that occur at later times are best explained by changes in stress. While some of the seismic activity is clearly induced by injection of fluids, also present is triggered seismicity that includes aftershock sequences, swarms of seismicity triggered by other earthquakes at The Geysers and clusters of multiple earthquakes. No basic differences are found between the source mechanisms of these different types of earthquakes.

  19. Land Use Induced Hydroclimatic Variability Over Large Deforested Areas in Southern Amazon Rainforest

    NASA Astrophysics Data System (ADS)

    Khanna, J.; Medvigy, D.

    2017-12-01

    Contemporary Amazonian deforestation, which occurs at scales of a few hundreds of kilometers, has been found to induce systematic changes in the regional dry season precipitation. The replacement of rough forest with smooth pasture induces a low level atmospheric convergence and uplift in the downwind and divergence and subsidence in the upwind deforested areas. The resulting precipitation change is about ±30% of the deforested area mean in the two regions respectively. Compared with the increase in non-precipitating cloudiness triggered by small scale clearings prevalent in the early phases of deforestation, this `dynamical mesoscale circulation' can have regional ecological impacts by altering precipitation seasonality and in turn ecosystem dynamics. However, the seasonality and variability of this phenomenon hasn't been studied. Using observations and numerical simulations this study investigates the relationships between the dynamical mechanism and the local- and continental-scale atmospheric conditions to understand the physical controls on this phenomenon on the inter-annual, inter-seasonal and daily time scales. We find that the strength of the dynamical mechanism is controlled mostly by regional scale thermal and dynamical conditions of the boundary layer and not the continental and global scale atmospheric state. The lifting condensation level (thermodynamic control) and wind speed (dynamic control) within the boundary layer have the largest and positive correlations with the dipole strength, which is true although not always significant across time scales. Due to this dependence it is found to be strongest during parts of the year when the atmosphere is relatively stable. Hence, overall this phenomenon is found to be the prevalent convective triggering mechanism during the dry and parts of transition seasons (especially spring), significantly affecting the hydroclimate during this period.

  20. Application of Fault Management Theory to the Quantitative Selection of a Launch Vehicle Abort Trigger Suite

    NASA Technical Reports Server (NTRS)

    Lo, Yunnhon; Johnson, Stephen B.; Breckenridge, Jonathan T.

    2014-01-01

    The theory of System Health Management (SHM) and of its operational subset Fault Management (FM) states that FM is implemented as a "meta" control loop, known as an FM Control Loop (FMCL). The FMCL detects that all or part of a system is now failed, or in the future will fail (that is, cannot be controlled within acceptable limits to achieve its objectives), and takes a control action (a response) to return the system to a controllable state. In terms of control theory, the effectiveness of each FMCL is estimated based on its ability to correctly estimate the system state, and on the speed of its response to the current or impending failure effects. This paper describes how this theory has been successfully applied on the National Aeronautics and Space Administration's (NASA) Space Launch System (SLS) Program to quantitatively estimate the effectiveness of proposed abort triggers so as to select the most effective suite to protect the astronauts from catastrophic failure of the SLS. The premise behind this process is to be able to quantitatively provide the value versus risk trade-off for any given abort trigger, allowing decision makers to make more informed decisions. All current and planned crewed launch vehicles have some form of vehicle health management system integrated with an emergency launch abort system to ensure crew safety. While the design can vary, the underlying principle is the same: detect imminent catastrophic vehicle failure, initiate launch abort, and extract the crew to safety. Abort triggers are the detection mechanisms that identify that a catastrophic launch vehicle failure is occurring or is imminent and cause the initiation of a notification to the crew vehicle that the escape system must be activated. While ensuring that the abort triggers provide this function, designers must also ensure that the abort triggers do not signal that a catastrophic failure is imminent when in fact the launch vehicle can successfully achieve orbit. That is, the abort triggers must have low false negative rates to be sure that real crew-threatening failures are detected, and also low false positive rates to ensure that the crew does not abort from non-crew-threatening launch vehicle behaviors. The analysis process described in this paper is a compilation of over six years of lessons learned and refinements from experiences developing abort triggers for NASA's Constellation Program (Ares I Project) and the SLS Program, as well as the simultaneous development of SHM/FM theory. The paper will describe the abort analysis concepts and process, developed in conjunction with SLS Safety and Mission Assurance (S&MA) to define a common set of mission phase, failure scenario, and Loss of Mission Environment (LOME) combinations upon which the SLS Loss of Mission (LOM) Probabilistic Risk Assessment (PRA) models are built. This abort analysis also requires strong coordination with the Multi-Purpose Crew Vehicle (MPCV) and SLS Structures and Environments (STE) to formulate a series of abortability tables that encapsulate explosion dynamics over the ascent mission phase. The design and assessment of abort conditions and triggers to estimate their Loss of Crew (LOC) Benefits also requires in-depth integration with other groups, including Avionics, Guidance, Navigation and Control(GN&C), the Crew Office, Mission Operations, and Ground Systems. The outputs of this analysis are a critical input to SLS S&MA's LOC PRA models. The process described here may well be the first full quantitative application of SHM/FM theory to the selection of a sensor suite for any aerospace system.

  1. Mechanism of force mode dip-pen nanolithography

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

    Yang, Haijun, E-mail: yanghaijun@sinap.ac.cn, E-mail: swguo@sjtu.edu.cn, E-mail: wanghuabin@cigit.ac.cn; Interfacial Water Division and Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, CAS, Shanghai 201800; Xie, Hui

    In this work, the underlying mechanism of the force mode dip-pen nanolithography (FMDPN) is investigated in depth by analyzing force curves, tapping mode deflection signals, and “Z-scan” voltage variations during the FMDPN. The operation parameters including the relative “trigger threshold” and “surface delay” parameters are vital to control the loading force and dwell time for ink deposition during FMDPN. A model is also developed to simulate the interactions between the atomic force microscope tip and soft substrate during FMDPN, and verified by its good performance in fitting our experimental data.

  2. Synchronization of Switched Neural Networks With Communication Delays via the Event-Triggered Control.

    PubMed

    Wen, Shiping; Zeng, Zhigang; Chen, Michael Z Q; Huang, Tingwen

    2017-10-01

    This paper addresses the issue of synchronization of switched delayed neural networks with communication delays via event-triggered control. For synchronizing coupled switched neural networks, we propose a novel event-triggered control law which could greatly reduce the number of control updates for synchronization tasks of coupled switched neural networks involving embedded microprocessors with limited on-board resources. The control signals are driven by properly defined events, which depend on the measurement errors and current-sampled states. By using a delay system method, a novel model of synchronization error system with delays is proposed with the communication delays and event-triggered control in the unified framework for coupled switched neural networks. The criteria are derived for the event-triggered synchronization analysis and control synthesis of switched neural networks via the Lyapunov-Krasovskii functional method and free weighting matrix approach. A numerical example is elaborated on to illustrate the effectiveness of the derived results.

  3. Careers and Organizational Labor Markets: Demographic Models of Organizational Behavior.

    ERIC Educational Resources Information Center

    Stewman, Shelby; Konda, Suresh L.

    1983-01-01

    Four organizational micro-structures and two triggering mechanisms that provide clues for assessing individual career prospects within an organization are identified. The four microstructures are grade ratios, vacancy chains, managerial selection preferences, and cohort size. The triggering mechanisms are growth and exit rates. (Author/AM)

  4. On the Control of Social Approach-Avoidance Behavior: Neural and Endocrine Mechanisms.

    PubMed

    Kaldewaij, Reinoud; Koch, Saskia B J; Volman, Inge; Toni, Ivan; Roelofs, Karin

    The ability to control our automatic action tendencies is crucial for adequate social interactions. Emotional events trigger automatic approach and avoidance tendencies. Although these actions may be generally adaptive, the capacity to override these emotional reactions may be key to flexible behavior during social interaction. The present chapter provides a review of the neuroendocrine mechanisms underlying this ability and their relation to social psychopathologies. Aberrant social behavior, such as observed in social anxiety or psychopathy, is marked by abnormalities in approach-avoidance tendencies and the ability to control them. Key neural regions involved in the regulation of approach-avoidance behavior are the amygdala, widely implicated in automatic emotional processing, and the anterior prefrontal cortex, which exerts control over the amygdala. Hormones, especially testosterone and cortisol, have been shown to affect approach-avoidance behavior and the associated neural mechanisms. The present chapter also discusses ways to directly influence social approach and avoidance behavior and will end with a research agenda to further advance this important research field. Control over approach-avoidance tendencies may serve as an exemplar of emotional action regulation and might have a great value in understanding the underlying mechanisms of the development of affective disorders.

  5. Modulation of occluding junctions alters the hematopoietic niche to trigger immune activation

    PubMed Central

    Khadilkar, Rohan J; Vogl, Wayne; Goodwin, Katharine

    2017-01-01

    Stem cells are regulated by signals from their microenvironment, or niche. During Drosophila hematopoiesis, a niche regulates prohemocytes to control hemocyte production. Immune challenges activate cell-signalling to initiate the cellular and innate immune response. Specifically, certain immune challenges stimulate the niche to produce signals that induce prohemocyte differentiation. However, the mechanisms that promote prohemocyte differentiation subsequent to immune challenges are poorly understood. Here we show that bacterial infection induces the cellular immune response by modulating occluding-junctions at the hematopoietic niche. Occluding-junctions form a permeability barrier that regulates the accessibility of prohemocytes to niche derived signals. The immune response triggered by infection causes barrier breakdown, altering the prohemocyte microenvironment to induce immune cell production. Moreover, genetically induced barrier ablation provides protection against infection by activating the immune response. Our results reveal a novel role for occluding-junctions in regulating niche-hematopoietic progenitor signalling and link this mechanism to immune cell production following infection. PMID:28841136

  6. Liquid Marble Coalescence and Triggered Microreaction Driven by Acoustic Levitation.

    PubMed

    Chen, Zhen; Zang, Duyang; Zhao, Liang; Qu, Mengfei; Li, Xu; Li, Xiaoguang; Li, Lixin; Geng, Xingguo

    2017-06-27

    Liquid marbles show promising potential for application in the microreactor field. Control of the coalescence between two or among multiple liquid marbles is critical; however, the successful merging of two isolated marbles is difficult because of their mechanically robust particle shells. In this work, the coalescence of multiple liquid marbles was achieved via acoustic levitation. The dynamic behaviors of the liquid marbles were monitored by a high-speed camera. Driven by the sound field, the liquid marbles moved toward each other, collided, and eventually coalesced into a larger single marble. The underlying mechanisms of this process were probed via sound field simulation and acoustic radiation pressure calculation. The results indicated that the pressure gradient on the liquid marble surface favors the formation of a liquid bridge between the liquid marbles, resulting in their coalescence. A preliminary indicator reaction was induced by the coalescence of dual liquid marbles, which suggests that expected chemical reactions can be successfully triggered with multiple reagents contained in isolated liquid marbles via acoustic levitation.

  7. Molecular mechanism of Mg2+-dependent gating in CorA

    NASA Astrophysics Data System (ADS)

    Dalmas, Olivier; Sompornpisut, Pornthep; Bezanilla, Francisco; Perozo, Eduardo

    2014-04-01

    CorA is the major transport system responsible for Mg2+ uptake in bacteria and can functionally substitute for its homologue Mrs2p in the yeast inner mitochondrial membrane. Although several CorA crystal structures are available, the molecular mechanism of Mg2+ uptake remains to be established. Here we use electron paramagnetic resonance spectroscopy, electrophysiology and molecular dynamic simulations to show that CorA is regulated by cytoplasmic Mg2+ acting as a ligand and elucidate the basic conformational rearrangements responsible for Mg2+-dependent gating. Mg2+ unbinding at the divalent cation sensor triggers a conformational change that leads to the inward motion of the stalk helix, which propagates to the pore-forming transmembrane helix TM1. Helical tilting and rotation in TM1 generates an iris-like motion that increases the diameter of the permeation pathway, triggering ion conduction. This work establishes the molecular basis of a Mg2+-driven negative feedback loop in CorA as the key physiological event controlling Mg2+ uptake and homeostasis in prokaryotes.

  8. Smart Coating for Corrosion Indication and Prevention: Recent Progress

    NASA Technical Reports Server (NTRS)

    Li, Wenyan; Hintze, Paul; Calle, Luz M.; Buhrow, Jerry; Curran, Jerry; Muehlberg, A. J.; Gelling, V. J.; Webster, D. C.; Croll, S. G.; Contu, F.; hide

    2009-01-01

    The authors are developing a smart coating system based on pH-triggered release microcapsules. These microcapsules can be incorporated into various coating systems for corrosion detection, protection and self-repair of mechanical coating damage. This paper will present the results from progress made to date in the controlled release properties of these microcapsules as well as in their corrosion indication and corrosion inhibition function.

  9. A triggered mechanism retrieves membrane in seconds after Ca(2+)- stimulated exocytosis in single pituitary cells

    PubMed Central

    1994-01-01

    In neuroendocrine cells, cytosolic Ca2+ triggers exocytosis in tens of milliseconds, yet known pathways of endocytic membrane retrieval take minutes. To test for faster retrieval mechanisms, we have triggered short bursts of exocytosis by flash photolysis of caged Ca2+, and have tracked subsequent retrieval by measuring the plasma membrane capacitance. We find that a limited amount of membrane can be retrieved with a time constant of 4 s at 21-26 degrees C, and that this occurs partially via structures larger than coated vesicles. This novel mechanism may be arrested at a late step. Incomplete retrieval structures then remain on the cell surface for minutes until the consequences of a renewed increase in cytosolic [Ca2+] disconnect them from the cell surface in < 1 s. Our results provide evidence for a rapid, triggered membrane retrieval pathway in excitable cells. PMID:8120090

  10. A MODEL FOR MAGNETICALLY COUPLED SYMPATHETIC ERUPTIONS

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

    Toeroek, T.; Titov, V. S.; Mikic, Z.

    2011-10-01

    Sympathetic eruptions on the Sun have been observed for several decades, but the mechanisms by which one eruption can trigger another remain poorly understood. We present a three-dimensional MHD simulation that suggests two possible magnetic trigger mechanisms for sympathetic eruptions. We consider a configuration that contains two coronal flux ropes located within a pseudo-streamer and one rope located next to it. A sequence of eruptions is initiated by triggering the eruption of the flux rope next to the streamer. The expansion of the rope leads to two consecutive reconnection events, each of which triggers the eruption of a flux ropemore » by removing a sufficient amount of overlying flux. The simulation qualitatively reproduces important aspects of the global sympathetic event on 2010 August 1 and provides a scenario for the so-called twin filament eruptions. The suggested mechanisms are also applicable for sympathetic eruptions occurring in other magnetic configurations.« less

  11. Stimuli-Responsive DNA-Based Hydrogels: From Basic Principles to Applications.

    PubMed

    Kahn, Jason S; Hu, Yuwei; Willner, Itamar

    2017-04-18

    The base sequence of nucleic acids encodes structural and functional information into the DNA biopolymer. External stimuli such as metal ions, pH, light, or added nucleic acid fuel strands provide triggers to reversibly switch nucleic acid structures such as metal-ion-bridged duplexes, i-motifs, triplex nucleic acids, G-quadruplexes, or programmed double-stranded hybrids of oligonucleotides (DNA). The signal-triggered oligonucleotide structures have been broadly applied to develop switchable DNA nanostructures and DNA machines, and these stimuli-responsive assemblies provide functional scaffolds for the rapidly developing area of DNA nanotechnology. Stimuli-responsive hydrogels undergoing signal-triggered hydrogel-to-solution transitions or signal-controlled stiffness changes attract substantial interest as functional matrices for controlled drug delivery, materials exhibiting switchable mechanical properties, acting as valves or actuators, and "smart" materials for sensing and information processing. The integration of stimuli-responsive oligonucleotides with hydrogel-forming polymers provides versatile means to exploit the functional information encoded in the nucleic acid sequences to yield stimuli-responsive hydrogels exhibiting switchable physical, structural, and chemical properties. Stimuli-responsive DNA-based nucleic acid structures are integrated in acrylamide polymer chains and reversible, switchable hydrogel-to-solution transitions of the systems are demonstrated by applying external triggers, such as metal ions, pH-responsive strands, G-quadruplex, and appropriate counter triggers that bridge and dissociate the polymer chains. By combining stimuli-responsive nucleic acid bridges with thermosensitive poly(N-isopropylacrylamide) (pNIPAM) chains, systems undergoing reversible solution ↔ hydrogel ↔ solid transitions are demonstrated. Specifically, by bridging acrylamide polymer chains by two nucleic acid functionalities, where one type of bridging unit provides a stimuli-responsive element and the second unit acts as internal "bridging memory", shape-memory hydrogels undergoing reversible and switchable transitions between shaped hydrogels and shapeless quasi-liquid states are demonstrated. By using stimuli-responsive hydrogel cross-linking units that can assemble the bridging units by two different input signals, the orthogonally-triggered functions of the shape-memory were shown. Furthermore, a versatile approach to assemble stimuli-responsive DNA-based acrylamide hydrogel films on surfaces is presented. The method involves the activation of the hybridization chain-reaction (HCR) by a surface-confined promoter strand, in the presence of acrylamide chains modified with two DNA hairpin structures and appropriate stimuli-responsive tethers. The resulting hydrogel-modified surfaces revealed switchable stiffness properties and signal-triggered catalytic functions. By applying the method to assemble the hydrogel microparticles, substrate-loaded, stimuli-responsive microcapsules are prepared. The signal-triggered DNA-based hydrogel microcapsules are applied as drug carriers for controlled release. The different potential applications and future perspectives of stimuli responsive hydrogels are discussed. Specifically, the use of these smart materials and assemblies as carriers for controlled drug release and as shape-memory matrices for information storage and inscription and the use of surface-confined stimuli-responsive hydrogels, exhibiting switchable stiffness properties, for catalysis and controlled growth of cells are discussed.

  12. Triggering Descending Pain Inhibition by Observing Ourselves or a Loved-One in Pain.

    PubMed

    Gougeon, Véronique; Gaumond, Isabelle; Goffaux, Philippe; Potvin, Stéphane; Marchand, Serge

    2016-03-01

    Recent studies demonstrate that empathy-evoked brain responses include the activation of brainstem structures responsible for triggering descending pain inhibition. Unfortunately, direct evidence linking empathy for pain and descending inhibitory controls (conditioned pain modulation) is lacking. This study, therefore, aimed to determine if the observation of ourselves or a loved-one in pain could activate descending pain inhibition without exposure to a noxious stimulation; which is otherwise required. Descending pain inhibition was triggered by immersing the right arm of participants (15 heterosexual couples; mean age±SE: 28.89±2.14) in a bath of cold water. The effects of empathy on descending pain inhibition were observed by immersing the right arm of participants in a bath of lukewarm water while having them watch a video of either themselves or their spouse during a previous nociceptive immersion. Immersion of the arm in a bath of lukewarm water without empathic (video) observation was also included as a control condition. A strong inhibitory response activated by the mere observation of the video of themselves or their spouse in pain without a nociceptive conditioning stimulus. Associative statistics also showed that strong pain catastrophizing responses while watching the video resulted in stronger pain inhibition. Moreover, high levels of empathy were associated with stronger pain inhibition, but only for women. This study showed that observing someone in pain triggers descending pain inhibition. Results also demonstrate how empathy and gender are affecting pain modulation mechanisms.

  13. Membrane cholesterol removal changes mechanical properties of cells and induces secretion of a specific pool of lysosomes.

    PubMed

    Hissa, Barbara; Pontes, Bruno; Roma, Paula Magda S; Alves, Ana Paula; Rocha, Carolina D; Valverde, Thalita M; Aguiar, Pedro Henrique N; Almeida, Fernando P; Guimarães, Allan J; Guatimosim, Cristina; Silva, Aristóbolo M; Fernandes, Maria C; Andrews, Norma W; Viana, Nathan B; Mesquita, Oscar N; Agero, Ubirajara; Andrade, Luciana O

    2013-01-01

    In a previous study we had shown that membrane cholesterol removal induced unregulated lysosomal exocytosis events leading to the depletion of lysosomes located at cell periphery. However, the mechanism by which cholesterol triggered these exocytic events had not been uncovered. In this study we investigated the importance of cholesterol in controlling mechanical properties of cells and its connection with lysosomal exocytosis. Tether extraction with optical tweezers and defocusing microscopy were used to assess cell dynamics in mouse fibroblasts. These assays showed that bending modulus and surface tension increased when cholesterol was extracted from fibroblasts plasma membrane upon incubation with MβCD, and that the membrane-cytoskeleton relaxation time increased at the beginning of MβCD treatment and decreased at the end. We also showed for the first time that the amplitude of membrane-cytoskeleton fluctuation decreased during cholesterol sequestration, showing that these cells become stiffer. These changes in membrane dynamics involved not only rearrangement of the actin cytoskeleton, but also de novo actin polymerization and stress fiber formation through Rho activation. We found that these mechanical changes observed after cholesterol sequestration were involved in triggering lysosomal exocytosis. Exocytosis occurred even in the absence of the lysosomal calcium sensor synaptotagmin VII, and was associated with actin polymerization induced by MβCD. Notably, exocytosis triggered by cholesterol removal led to the secretion of a unique population of lysosomes, different from the pool mobilized by actin depolymerizing drugs such as Latrunculin-A. These data support the existence of at least two different pools of lysosomes with different exocytosis dynamics, one of which is directly mobilized for plasma membrane fusion after cholesterol removal.

  14. Membrane Cholesterol Removal Changes Mechanical Properties of Cells and Induces Secretion of a Specific Pool of Lysosomes

    PubMed Central

    Roma, Paula Magda S.; Alves, Ana Paula; Rocha, Carolina D.; Valverde, Thalita M.; Aguiar, Pedro Henrique N.; Almeida, Fernando P.; Guimarães, Allan J.; Guatimosim, Cristina; Silva, Aristóbolo M.; Fernandes, Maria C.; Andrews, Norma W.; Viana, Nathan B.; Mesquita, Oscar N.; Agero, Ubirajara; Andrade, Luciana O.

    2013-01-01

    In a previous study we had shown that membrane cholesterol removal induced unregulated lysosomal exocytosis events leading to the depletion of lysosomes located at cell periphery. However, the mechanism by which cholesterol triggered these exocytic events had not been uncovered. In this study we investigated the importance of cholesterol in controlling mechanical properties of cells and its connection with lysosomal exocytosis. Tether extraction with optical tweezers and defocusing microscopy were used to assess cell dynamics in mouse fibroblasts. These assays showed that bending modulus and surface tension increased when cholesterol was extracted from fibroblasts plasma membrane upon incubation with MβCD, and that the membrane-cytoskeleton relaxation time increased at the beginning of MβCD treatment and decreased at the end. We also showed for the first time that the amplitude of membrane-cytoskeleton fluctuation decreased during cholesterol sequestration, showing that these cells become stiffer. These changes in membrane dynamics involved not only rearrangement of the actin cytoskeleton, but also de novo actin polymerization and stress fiber formation through Rho activation. We found that these mechanical changes observed after cholesterol sequestration were involved in triggering lysosomal exocytosis. Exocytosis occurred even in the absence of the lysosomal calcium sensor synaptotagmin VII, and was associated with actin polymerization induced by MβCD. Notably, exocytosis triggered by cholesterol removal led to the secretion of a unique population of lysosomes, different from the pool mobilized by actin depolymerizing drugs such as Latrunculin-A. These data support the existence of at least two different pools of lysosomes with different exocytosis dynamics, one of which is directly mobilized for plasma membrane fusion after cholesterol removal. PMID:24376622

  15. Investigation of Potential Triggered Tremor in Latin America and the Caribbean

    NASA Astrophysics Data System (ADS)

    Gonzalez-Huizar, H.; Velasco, A. A.; Peng, Z.

    2012-12-01

    Recent observations have shown that seismic waves generate transient stresses capable of triggering earthquakes and tectonic (or non-volcanic) tremor far away from the original earthquake source. However, the mechanisms behind remotely triggered seismicity still remain unclear. Triggered tremor signals can be particularly useful in investigating remote triggering processes, since in many cases, the tremor pulses are very clearly modulated by the passing surface waves. The temporal stress changes (magnitude and orientation) caused by seismic waves at the tremor source region can be calculated and correlated with tremor pulses, which allows for exploring the stresses involved in the triggering process. Some observations suggest that triggered and ambient tremor signals are generated under similar physical conditions; thus, investigating triggered tremor might also provide important clues on how and under what conditions ambient tremor signals generate. In this work we present some of the results and techniques we employ in the research of potential cases of triggered tectonic tremor in Latin America and the Caribbean. This investigation includes: (1) the triggered tremor detection, with the use of specific signal filters; (2) localization of the sources, using uncommon techniques like time reversal signals; (3) and the analysis of the stress conditions under which they are generated, by modeling the triggering waves related dynamic stress. Our results suggest that tremor can be dynamically triggered by both Love and Rayleigh waves and in broad variety of tectonic environments depending strongly on the dynamic stress amplitude and orientation. Investigating remotely triggered seismicity offers the opportunity to improve our knowledge about deformation mechanisms and the physics of rupture.

  16. Conflict-Triggered Top-Down Control: Default Mode, Last Resort, or No Such Thing?

    ERIC Educational Resources Information Center

    Bugg, Julie M.

    2014-01-01

    The conflict monitoring account posits that globally high levels of conflict trigger engagement of top-down control; however, recent findings point to the mercurial nature of top-down control in high conflict contexts. The current study examined the potential moderating effect of associative learning on conflict-triggered top-down control…

  17. Targeted antioxidant therapies in hyperglycemia-mediated endothelial dysfunction.

    PubMed

    de Haan, Judy B; Cooper, Mark E

    2011-01-01

    Although intensive glycaemic and blood pressure control have reduced the risks of micro- and macrovascular complications, diabetes remains a major cause of cardiovascular events, end-stage renal failure, blindness and neuropathy. It is therefore imperative to understand the underlying mechanisms and to establish effective treatments to prevent, retard or reverse diabetic complications. One area of increased focus is the diabetic vascular endothelium. Hyperglycaemia triggers a cascade of events, not least an increase in reactive oxygen species (ROS) leading to enhanced oxidative stress, with its negative impact on endothelial function. In this review, we explore a unifying hypothesis that increased glucose-mediated ROS leads to endothelial dysfunction as the underpinning causative event triggering accelerated micro- and macrovascular complications. In particular, the consequences of deficiencies in the antioxidant enzyme, glutathione peroxidase, on endothelial dysfunction as a trigger of diabetic micro- and macrovascular complications, will be reviewed. Furthermore, novel antioxidant therapies will be highlighted. Specifically, use of Gpx1-mimetics holds promise as a targeted antioxidant approach and an alternative adjunct therapy to reduce diabetic complications.

  18. Quaternary base-level drops and trigger mechanisms in a closed basin: Geomorphic and sedimentological studies of the Gastre Basin, Argentina

    NASA Astrophysics Data System (ADS)

    Bilmes, Andrés; Veiga, Gonzalo D.; Ariztegui, Daniel; Castelltort, Sébastien; D'Elia, Leandro; Franzese, Juan R.

    2017-04-01

    Evaluating the role of tectonics and climate as possible triggering mechanisms of landscape reconfigurations is essential for paleoenvironmental and paleoclimatic reconstructions. In this study an exceptional receptive closed Quaternary system of Patagonia (the Gastre Basin) is described, and examined in order to analyze factors triggering base-level drops. Based on a geomorphological approach, which includes new tectonic geomorphology investigations combined with sedimentological and stratigraphic analysis, three large-scale geomorphological systems were identified, described and linked to two major lake-level highstands preserved in the basin. The results indicate magnitudes of base-level drops that are several orders of magnitude greater than present-day water-level fluctuations, suggesting a triggering mechanism not observed in recent times. Direct observations indicating the occurrence of Quaternary faults were not recorded in the region. In addition, morphometric analyses that included mountain front sinuosity, valley width-height ratio, and fan apex position dismiss tectonic fault activity in the Gastre Basin during the middle Pleistocene-Holocene. Therefore, we suggest here that upper Pleistocene climate changes may have been the main triggering mechanism of base-level falls in the Gastre Basin as it is observed in other closed basins of central Patagonia (i.e., Carri Laufquen Basin).

  19. Epigenetic mechanisms of memory formation and reconsolidation.

    PubMed

    Jarome, Timothy J; Lubin, Farah D

    2014-11-01

    Memory consolidation involves transcriptional control of genes in neurons to stabilize a newly formed memory. Following retrieval, a once consolidated memory destabilizes and again requires gene transcription changes in order to restabilize, a process referred to as reconsolidation. Understanding the molecular mechanisms of gene transcription during the consolidation and reconsolidation processes could provide crucial insights into normal memory formation and memory dysfunction associated with psychiatric disorders. In the past decade, modifications of epigenetic markers such as DNA methylation and posttranslational modifications of histone proteins have emerged as critical transcriptional regulators of gene expression during initial memory formation and after retrieval. In light of the rapidly growing literature in this exciting area of research, we here examine the most recent and latest evidence demonstrating how memory acquisition and retrieval trigger epigenetic changes during the consolidation and reconsolidation phases to impact behavior. In particular we focus on the reconsolidation process, where we discuss the already identified epigenetic regulators of gene transcription during memory reconsolidation, while exploring other potential epigenetic modifications that may also be involved, and expand on how these epigenetic modifications may be precisely and temporally controlled by important signaling cascades critical to the reconsolidation process. Finally, we explore the possibility that epigenetic mechanisms may serve to regulate a system or circuit level reconsolidation process and may be involved in retrieval-dependent memory updating. Hence, we propose that epigenetic mechanisms coordinate changes in neuronal gene transcription, not only during the initial memory consolidation phase, but are triggered by retrieval to regulate molecular and cellular processes during memory reconsolidation. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Epigenetic Mechanisms of Memory Formation and Reconsolidation

    PubMed Central

    Jarome, Timothy J.; Lubin, Farah D.

    2014-01-01

    Memory consolidation involves transcriptional control of genes in neurons to stabilize a newly formed memory. Following retrieval, a once consolidated memory destabilizes and again requires gene transcription changes in order to restabilize, a process referred to as reconsolidation. Understanding the molecular mechanisms of gene transcription during the consolidation and reconsolidation processes could provide crucial insights into normal memory formation and memory dysfunction associated with psychiatric disorders. In the past decade, modifications of epigenetic markers such as DNA methylation and posttranslational modifications of histone proteins have emerged as critical transcriptional regulators of gene expression during initial memory formation and after retrieval. In light of the rapidly growing literature in this exciting area of research, we here examine the most recent and latest evidence demonstrating how memory acquisition and retrieval trigger epigenetic changes during the consolidation and reconsolidation phases to impact behavior. In particular we focus on the reconsolidation process, where we discuss the already identified epigenetic regulators of gene transcription during memory reconsolidation, while exploring other potential epigenetic modifications that may also be involved, and expand on how these epigenetic modifications may be precisely and temporally controlled by important signaling cascades critical to the reconsolidation process. Finally, we explore the possibility that epigenetic mechanisms may serve to regulate a system or circuit level reconsolidation process and may be involved in retrieval-dependent memory updating. Hence, we propose that epigenetic mechanisms coordinate changes in neuronal gene transcription, not only during the initial memory consolidation phase, but are triggered by retrieval to regulate molecular and cellular processes during memory reconsolidation. PMID:25130533

  1. Rejection triggers liver transplant tolerance: Involvement of mesenchyme-mediated immune control mechanisms in mice.

    PubMed

    Morita, Miwa; Joyce, Daniel; Miller, Charles; Fung, John J; Lu, Lina; Qian, Shiguang

    2015-09-01

    Liver tolerance was initially recognized by the spontaneous acceptance of liver allografts in many species. The underlying mechanisms are not completely understood. However, liver transplant (LT) tolerance absolutely requires interferon (IFN)-γ, a rejection-associated inflammatory cytokine. In this study, we investigated the rejection of liver allografts deficient in the IFN-γ receptor and reveal that the liver graft is equipped with machineries capable of counterattacking the host immune response through a mesenchyme-mediated immune control (MMIC) mechanism. MMIC is triggered by T effector (Tef) cell-derived IFN-γ that drives expression of B7-H1 on graft mesenchymal cells leading to Tef cell apoptosis. We describe the negative feedback loop between graft mesenchymal and Tef cells that ultimately results in LT tolerance. Comparable elevations of T-regulatory cells and myeloid-derived suppressor cells were observed in both rejection and tolerance groups and were not dependent on IFN-γ stimulation, suggesting a critical role of Tef cell elimination in tolerance induction. We identify potent MMIC activity in hepatic stellate cells and liver sinusoidal endothelial cells. MMIC is unlikely exclusive to the liver, given that spontaneous acceptance of kidney allografts has been reported, although less commonly, probably reflecting variance in MMIC activity. MMIC may represent an important homeostatic mechanism that supports peripheral tolerance and could be a target for the prevention and treatment of transplant rejection. This study highlights that the graft is an active participant in the equipoise between tolerance and rejection and warrants more attention in the search for tolerance biomarkers. © 2015 by the American Association for the Study of Liver Diseases.

  2. Rejection Triggers Liver Transplant Tolerance: Involvements of Mesenchyme-Mediated Immune Control Mechanisms

    PubMed Central

    Morita, Miwa; Joyce, Daniel; Miller, Charles; Fung, John J.; Lu, Lina; Qian, Shiguang

    2015-01-01

    Liver tolerance was initially recognized by the spontaneous acceptance of liver allograft in many species. The underlying mechanisms are not completely understood. We have been inspired by an unexpected phenomenon that the liver transplant tolerance absolutely requires interferon (IFN)-γ, a rejection-associated inflammatory cytokine. In this study, we investigate the rejection of liver allografts deficient in IFN-γ receptor and reveal that the liver graft is equipped with machineries capable of counterattacking the host immune response through a mesenchyme-mediated immune control (MMIC) mechanism. MMIC is triggered by T effectors (Tef) cell-derived IFN-γ to drive the expression of B7-H1 on graft mesenchymal cells leading to Tef cell apoptosis. We describe the negative feedback loop between graft mesenchymal and Tef cells that ultimately results in liver transplant tolerance. Comparable elevations of T regulatory cells and myeloid-derived suppressor cells are seen in both rejection and tolerance groups, and are not dependent on IFN-γ stimulation, suggesting a critical role of Tef cell elimination in tolerance induction. We identify potent MMIC activity in hepatic stellate cells and liver sinusoidal endothelial cells. MMIC is unlikely exclusive to the liver, as spontaneous acceptance of kidney allografts has been reported, although less commonly, probably reflecting variance in MMIC activity. MMCI may represent an important homeostatic mechanism that supports peripheral tolerance, and could be a target for the prevention and treatment of transplant rejection. This study highlights that the graft is actively participant in the equipoise between tolerance and rejection and warrants more attention in the search for tolerance biomarkers. PMID:25998530

  3. Mechanisms of haptoglobin protection against hemoglobin peroxidation triggered endothelial damage.

    PubMed

    Schaer, C A; Deuel, J W; Bittermann, A G; Rubio, I G; Schoedon, G; Spahn, D R; Wepf, R A; Vallelian, F; Schaer, D J

    2013-11-01

    Extracellular hemoglobin (Hb) has been recognized as a disease trigger in hemolytic conditions such as sickle cell disease, malaria, and blood transfusion. In vivo, many of the adverse effects of free Hb can be attenuated by the Hb scavenger acute-phase protein haptoglobin (Hp). The primary physiologic disturbances that can be caused by free Hb are found within the cardiovascular system and Hb-triggered oxidative toxicity toward the endothelium has been promoted as a potential mechanism. The molecular mechanisms of this toxicity as well as of the protective activities of Hp are not yet clear. Within this study, we systematically investigated the structural, biochemical, and cell biologic nature of Hb toxicity in an endothelial cell system under peroxidative stress. We identified two principal mechanisms of oxidative Hb toxicity that are mediated by globin degradation products and by modified lipoprotein species, respectively. The two damage pathways trigger diverse and discriminative inflammatory and cytotoxic responses. Hp provides structural stabilization of Hb and shields Hb's oxidative reactions with lipoproteins, providing dramatic protection against both pathways of toxicity. By these mechanisms, Hp shifts Hb's destructive pseudo-peroxidative reaction to a potential anti-oxidative function during peroxidative stress.

  4. Evaluating the Mechanisms of Light-Triggered siRNA Release from Nanoshells for Temporal Control Over Gene Regulation.

    PubMed

    Riley, Rachel S; Dang, Megan N; Billingsley, Margaret M; Abraham, Baxter; Gundlach, Lars; Day, Emily S

    2018-06-13

    The ability to regulate intracellular gene expression with exogenous nucleic acids such as small interfering RNAs (siRNAs) has substantial potential to improve the study and treatment of disease. However, most transfection agents and nanoparticle-based carriers that are used for the intracellular delivery of nucleic acids cannot distinguish between diseased and healthy cells, which may cause them to yield unintended widespread gene regulation. An ideal delivery system would only silence targeted proteins in diseased tissue in response to an external stimulus. To enable spatiotemporal control over gene silencing, researchers have begun to develop nucleic acid-nanoparticle conjugates that keep their nucleic acid cargo inactive until it is released from the nanoparticle on-demand by externally applied near-infrared laser light. This strategy can overcome several limitations of other nucleic acid delivery systems, but the mechanisms by which these platforms operate remain ill understood. Here, we perform a detailed investigation of the mechanisms by which silica core/gold shell nanoshells (NSs) release conjugated siRNA upon excitation with either pulsed or continuous wave (CW) near-infrared (NIR) light, with the goal of providing insight into how these nanoconjugates can enable on-demand gene regulation. We demonstrate that siRNA release from NSs upon pulsed laser irradiation is a temperature-independent process that is substantially more efficient than siRNA release triggered by CW irradiation. Contrary to literature, which suggests that only pulsed irradiation releases siRNA duplexes, we found that both modes of irradiation release a mixture of siRNA duplexes and single-stranded oligonucleotides, but that pulsed irradiation results in a higher percentage of released duplexes. To demonstrate that the siRNA released from NSs upon pulsed irradiation remains functional, we evaluated the use of NSs coated with green fluorescent protein (GFP)-targeted siRNA (siGFP-NS) for on-demand knockdown of GFP in cells. We found that GFP-expressing cells treated with siGFP-NS and irradiated with a pulsed laser experienced a 33% decrease in GFP expression compared to cells treated with no laser. Further, we observed that light-triggered gene silencing mediated by siGFP-NS is more potent than using commercial transfection agents to deliver siRNA into cells. This work provides unprecedented insight into the mechanisms by which plasmonic NSs release siRNA upon light irradiation and demonstrates the importance of thoroughly characterizing photoresponsive nanosystems for applications in triggered gene regulation.

  5. Carbon monoxide – physiology, detection and controlled release

    PubMed Central

    Heinemann, Stefan H.; Hoshi, Toshinori; Westerhausen, Matthias

    2014-01-01

    Carbon monoxide (CO) is increasingly recognized as a cell-signalling molecule akin to nitric oxide (NO). CO has attracted particular attention as a potential therapeutic agent because of its reported anti-hypertensive, anti-inflammatory and cell-protective effects. We discuss recent progress in identifying new effector systems and elucidating the mechanisms of action of CO on, e.g., ion channels, as well as the design of novel methods to monitor CO in cellular environments. We also report on recent developments in the area of CO-releasing molecules (CORMs) and materials for controlled CO application. Novel triggers for CO release, metal carbonyls and degradation mechanisms of CORMs, are highlighted. In addition, potential formulations of CORMs for targeted CO release are discussed. PMID:24556640

  6. Tremor evidence for dynamically triggered creep events on the deep San Andreas Fault

    NASA Astrophysics Data System (ADS)

    Peng, Z.; Shelly, D. R.; Hill, D. P.; Aiken, C.

    2010-12-01

    Deep tectonic tremor has been observed along major subduction zones and the San Andreas fault (SAF) in central and southern California. It appears to reflect deep fault slip, and it is often seen to be triggered by small stresses, including passing seismic waves from large regional and teleseismic earthquakes. Here we examine tremor activity along the Parkfield-Cholame section of the SAF from mid-2001 to early 2010, scrutinizing its relationship with regional and teleseismic earthquakes. Based on similarities in the shape and timing of seismic waveforms, we conclude that triggered and ambient tremor share common sources and a common physical mechanism. Utilizing this similarity in waveforms, we detect tremor triggered by numerous large events, including previously unreported triggering from the recent 2009 Mw7.3 Honduras, 2009 Mw8.1 Samoa, and 2010 Mw8.8 Chile earthquakes at teleseismic distances, and the relatively small 2007 Mw5.4 Alum Rock and 2008 Mw5.4 Chino Hills earthquakes at regional distances. We also find multiple examples of systematic migration in triggered tremor, similar to ambient tremor migration episodes observed at other times. Because these episodes propagate much more slowly than the triggering waves, the migration likely reflects a small, triggered creep event. As with ambient tremor bursts, triggered tremor at times persists for multiple days, probably indicating a somewhat larger creep event. This activity provides a clear example of delayed dynamic triggering, with a mechanism perhaps also relevant for triggering of regular earthquakes.

  7. Contactless, photoinitiated snap-through in azobenzene-functionalized polymers

    PubMed Central

    Shankar, M. Ravi; Smith, Matthew L.; Tondiglia, Vincent P.; Lee, Kyung Min; McConney, Michael E.; Wang, David H.; Tan, Loon-Seng; White, Timothy J.

    2013-01-01

    Photomechanical effects in polymeric materials and composites transduce light into mechanical work. The ability to control the intensity, polarization, placement, and duration of light irradiation is a distinctive and potentially useful tool to tailor the location, magnitude, and directionality of photogenerated mechanical work. Unfortunately, the work generated from photoresponsive materials is often slow and yields very small power densities, which diminish their potential use in applications. Here, we investigate photoinitiated snap-through in bistable arches formed from samples composed of azobenzene-functionalized polymers (both amorphous polyimides and liquid crystal polymer networks) and report orders-of-magnitude enhancement in actuation rates (approaching 102 mm/s) and powers (as much as 1 kW/m3). The contactless, ultra-fast actuation is observed at irradiation intensities <<100 mW/cm2. Due to the bistability and symmetry of the snap-through, reversible and bidirectional actuation is demonstrated. A model is developed to elucidate the underlying mechanics of the snap-through, specifically focusing on isolating the role of sample geometry, mechanical properties of the materials, and photomechanical strain. Using light to trigger contactless, ultrafast actuation in an otherwise passive structure is a potentially versatile tool to use in mechanical design at the micro-, meso-, and millimeter scales as actuators, as well as switches that can be triggered from large standoff distances, impulse generators for microvehicles, microfluidic valves and mixers in laboratory-on-chip devices, and adaptive optical elements. PMID:24190994

  8. Contactless, photoinitiated snap-through in azobenzene-functionalized polymers.

    PubMed

    Shankar, M Ravi; Smith, Matthew L; Tondiglia, Vincent P; Lee, Kyung Min; McConney, Michael E; Wang, David H; Tan, Loon-Seng; White, Timothy J

    2013-11-19

    Photomechanical effects in polymeric materials and composites transduce light into mechanical work. The ability to control the intensity, polarization, placement, and duration of light irradiation is a distinctive and potentially useful tool to tailor the location, magnitude, and directionality of photogenerated mechanical work. Unfortunately, the work generated from photoresponsive materials is often slow and yields very small power densities, which diminish their potential use in applications. Here, we investigate photoinitiated snap-through in bistable arches formed from samples composed of azobenzene-functionalized polymers (both amorphous polyimides and liquid crystal polymer networks) and report orders-of-magnitude enhancement in actuation rates (approaching 10(2) mm/s) and powers (as much as 1 kW/m(3)). The contactless, ultra-fast actuation is observed at irradiation intensities <100 mW/cm(2). Due to the bistability and symmetry of the snap-through, reversible and bidirectional actuation is demonstrated. A model is developed to elucidate the underlying mechanics of the snap-through, specifically focusing on isolating the role of sample geometry, mechanical properties of the materials, and photomechanical strain. Using light to trigger contactless, ultrafast actuation in an otherwise passive structure is a potentially versatile tool to use in mechanical design at the micro-, meso-, and millimeter scales as actuators, as well as switches that can be triggered from large standoff distances, impulse generators for microvehicles, microfluidic valves and mixers in laboratory-on-chip devices, and adaptive optical elements.

  9. Degassing during quiescence as a trigger of magma ascent and volcanic eruptions.

    PubMed

    Girona, Társilo; Costa, Fidel; Schubert, Gerald

    2015-12-15

    Understanding the mechanisms that control the start-up of volcanic unrest is crucial to improve the forecasting of eruptions at active volcanoes. Among the most active volcanoes in the world are the so-called persistently degassing ones (e.g., Etna, Italy; Merapi, Indonesia), which emit massive amounts of gas during quiescence (several kilotonnes per day) and erupt every few months or years. The hyperactivity of these volcanoes results from frequent pressurizations of the shallow magma plumbing system, which in most cases are thought to occur by the ascent of magma from deep to shallow reservoirs. However, the driving force that causes magma ascent from depth remains unknown. Here we demonstrate that magma ascent can be triggered by the passive release of gas during quiescence, which induces the opening of pathways connecting deep and shallow magma reservoirs. This top-down mechanism for volcanic eruptions contrasts with the more common bottom-up mechanisms in which magma ascent is only driven by processes occurring at depth. A cause-effect relationship between passive degassing and magma ascent can explain the fact that repose times are typically much longer than unrest times preceding eruptions, and may account for the so frequent unrest episodes of persistently degassing volcanoes.

  10. GABAergic Neurons of the Central Amygdala Promote Cataplexy

    PubMed Central

    Agostinelli, Lindsay J.; Lowell, Bradford B.

    2017-01-01

    Narcolepsy is characterized by chronic sleepiness and cataplexy—sudden muscle paralysis triggered by strong, positive emotions. This condition is caused by a lack of orexin (hypocretin) signaling, but little is known about the neural mechanisms that mediate cataplexy. The amygdala regulates responses to rewarding stimuli and contains neurons active during cataplexy. In addition, lesions of the amygdala reduce cataplexy. Because GABAergic neurons of the central nucleus of the amygdala (CeA) target brainstem regions known to regulate muscle tone, we hypothesized that these cells promote emotion-triggered cataplexy. We injected adeno-associated viral vectors coding for Cre-dependent DREADDs or a control vector into the CeA of orexin knock-out mice crossed with vGAT-Cre mice, resulting in selective expression of the excitatory hM3 receptor or the inhibitory hM4 receptor in GABAergic neurons of the CeA. We measured sleep/wake behavior and cataplexy after injection of saline or the hM3/hM4 ligand clozapine-N-oxide (CNO) under baseline conditions and under conditions that should elicit positive emotions. In mice expressing hM3, CNO approximately doubled the amount of cataplexy in the first 3 h after dosing under baseline conditions. Rewarding stimuli (chocolate or running wheels) also increased cataplexy, but CNO produced no further increase. In mice expressing hM4, CNO reduced cataplexy in the presence of chocolate or running wheels. These results demonstrate that GABAergic neurons of the CeA are sufficient and necessary for the production of cataplexy in mice, and they likely are a key part of the mechanism through which positive emotions trigger cataplexy. SIGNIFICANCE STATEMENT Cataplexy is one of the major symptoms of narcolepsy, but little is known about how strong, positive emotions trigger these episodes of muscle paralysis. Prior research shows that amygdala neurons are active during cataplexy and cataplexy is reduced by lesions of the amygdala. We found that cataplexy is substantially increased by selective activation of GABAergic neurons in the central nucleus of the amygdala (CeA). We also demonstrate that inhibition of these neurons reduces reward-promoted cataplexy. These results build upon prior work to establish the CeA as a crucial element in the neural mechanisms of cataplexy. These results demonstrate the importance of the CeA in regulating responses to rewarding stimuli, shedding light on the broader neurobiology of emotions and motor control. PMID:28235898

  11. Long term real-time monitoring of large alpine rockslides by GB-InSAR: mechanisms, triggers, scenario assessment and Early Warning

    NASA Astrophysics Data System (ADS)

    Crosta, G. B.; Agliardi, F.; Sosio, R.; Rivolta, C.; Leva, D.; Dei Cas, L.

    2012-04-01

    Large rockslides in alpine valleys can undergo catastrophic evolution, posing extraordinary risks to settlements, lives and critical infrastructures. These phenomena are controlled by a complex interplay of lithological, structural, hydrological and meteo-climatic factors, which eventually result in: complex triggering mechanisms and kinematics, highly variable activity, regressive to progressive trends with superimposed acceleration and deceleration periods related to rainfall and snowmelt. Managing large rockslide risk remains challenging, due the high uncertainty related to their geological model and dynamics. In this context, the most promising approach to constrain rockslide kinematics, establish correlations with triggering factors, and predict future displacements, velocity and acceleration, and eventually possible final collapse is based on the analysis and modelling of long-term series of monitoring data. More than traditional monitoring activities, remote sensing represents an important tool aimed at describing local rockslide displacements and kinematics, at distinguishing rates of activity, and providing real time data suitable for early warning. We analyze a long term monitoring dataset collected for a deep-seated rockslide (Ruinon, Lombardy, Italy), actively monitored since 1997 through an in situ monitoring network (topographic and GPS, wire extensometers and distometer baselines) and since 2006 by a ground based radar (GB-InSAR). Monitoring allowed to set-up and update the geological model, identify rockslide extent and geometry, analyze its sensitivity to seasonal changes and their impact on the reliability and EW potential of monitoring data. GB-InSAR data allowed to identify sub-areas with different behaviors associated to outcropping bedrock and thick debris cover, and to set-up a "virtual monitoring network" by a posteriori selection of critical locations. Resulting displacement time series provide a large amount of information even in debris-covered areas, where traditional monitoring fails. Such spatially-distributed, improved information, validated by selected ground-based measurements, allowed to establish new velocity thresholds for EW purposes. Relationships between rainfall and displacement rates allowed to identify different possible failure mechanisms and to constrain the applicability of rainfall EW thresholds. Comparison with temperature and snow melting time series allowed to clarify the sensitivity of the rockslide movement to these controlling factors. Finally, the recognition of the sensitivity to all these factors allowed us to accomplish a more complete hazard assessment by defining different failure scenarios and the associated triggering thresholds.

  12. Phosphatidylserine Exposure Controls Viral Innate Immune Responses by Microglia.

    PubMed

    Tufail, Yusuf; Cook, Daniela; Fourgeaud, Lawrence; Powers, Colin J; Merten, Katharina; Clark, Charles L; Hoffman, Elizabeth; Ngo, Alexander; Sekiguchi, Kohei J; O'Shea, Clodagh C; Lemke, Greg; Nimmerjahn, Axel

    2017-02-08

    Microglia are the intrinsic immune sentinels of the central nervous system. Their activation restricts tissue injury and pathogen spread, but in some settings, including viral infection, this response can contribute to cell death and disease. Identifying mechanisms that control microglial responses is therefore an important objective. Using replication-incompetent adenovirus 5 (Ad5)-based vectors as a model, we investigated the mechanisms through which microglia recognize and respond to viral uptake. Transgenic, immunohistochemical, molecular-genetic, and fluorescence imaging approaches revealed that phosphatidylserine (PtdSer) exposure on the outer leaflet of transduced cells triggers their engulfment by microglia through TAM receptor-dependent mechanisms. We show that inhibition of phospholipid scramblase 1 (PLSCR1) activity reduces intracellular calcium dysregulation, prevents PtdSer externalization, and enables months-long protection of vector-transduced, transgene-expressing cells from microglial phagocytosis. Our study identifies PLSCR1 as a potent target through which the innate immune response to viral vectors, and potentially other stimuli, may be controlled. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Event-Triggered Adaptive Dynamic Programming for Continuous-Time Systems With Control Constraints.

    PubMed

    Dong, Lu; Zhong, Xiangnan; Sun, Changyin; He, Haibo

    2016-08-31

    In this paper, an event-triggered near optimal control structure is developed for nonlinear continuous-time systems with control constraints. Due to the saturating actuators, a nonquadratic cost function is introduced and the Hamilton-Jacobi-Bellman (HJB) equation for constrained nonlinear continuous-time systems is formulated. In order to solve the HJB equation, an actor-critic framework is presented. The critic network is used to approximate the cost function and the action network is used to estimate the optimal control law. In addition, in the proposed method, the control signal is transmitted in an aperiodic manner to reduce the computational and the transmission cost. Both the networks are only updated at the trigger instants decided by the event-triggered condition. Detailed Lyapunov analysis is provided to guarantee that the closed-loop event-triggered system is ultimately bounded. Three case studies are used to demonstrate the effectiveness of the proposed method.

  14. Influences of Duration of Inspiratory Effort, Respiratory Mechanics, and Ventilator Type on Asynchrony With Pressure Support and Proportional Assist Ventilation.

    PubMed

    Vasconcelos, Renata S; Sales, Raquel P; Melo, Luíz H de P; Marinho, Liégina S; Bastos, Vasco Pd; Nogueira, Andréa da Nc; Ferreira, Juliana C; Holanda, Marcelo A

    2017-05-01

    Pressure support ventilation (PSV) is often associated with patient-ventilator asynchrony. Proportional assist ventilation (PAV) offers inspiratory assistance proportional to patient effort, minimizing patient-ventilator asynchrony. The objective of this study was to evaluate the influence of respiratory mechanics and patient effort on patient-ventilator asynchrony during PSV and PAV plus (PAV+). We used a mechanical lung simulator and studied 3 respiratory mechanics profiles (normal, obstructive, and restrictive), with variations in the duration of inspiratory effort: 0.5, 1.0, 1.5, and 2.0 s. The Auto-Trak system was studied in ventilators when available. Outcome measures included inspiratory trigger delay, expiratory trigger asynchrony, and tidal volume (V T ). Inspiratory trigger delay was greater in the obstructive respiratory mechanics profile and greatest with a effort of 2.0 s (160 ms); cycling asynchrony, particularly delayed cycling, was common in the obstructive profile, whereas the restrictive profile was associated with premature cycling. In comparison with PSV, PAV+ improved patient-ventilator synchrony, with a shorter triggering delay (28 ms vs 116 ms) and no cycling asynchrony in the restrictive profile. V T was lower with PAV+ than with PSV (630 mL vs 837 mL), as it was with the single-limb circuit ventilator (570 mL vs 837 mL). PAV+ mode was associated with longer cycling delays than were the other ventilation modes, especially for the obstructive profile and higher effort values. Auto-Trak eliminated automatic triggering. Mechanical ventilation asynchrony was influenced by effort, respiratory mechanics, ventilator type, and ventilation mode. In PSV mode, delayed cycling was associated with shorter effort in obstructive respiratory mechanics profiles, whereas premature cycling was more common with longer effort and a restrictive profile. PAV+ prevented premature cycling but not delayed cycling, especially in obstructive respiratory mechanics profiles, and it was associated with a lower V T . Copyright © 2017 by Daedalus Enterprises.

  15. Identifying and Evaluating Possible Trigger Mechanisms for Glacial Lake Outburst Floods in the Hindu Kush Himalayas Using Remote Sensing Satellite Data

    NASA Astrophysics Data System (ADS)

    Hess, T. G.; Haritashya, U. K.

    2014-12-01

    Glacierized basins in high-altitude and mountainous areas, such as the Himalayas, have seen an increase in the number of glacial lakes over the years as a result of a changing climate. As the meltwater becomes more prevalent, the runoff can accumulate in a depression left behind by the receding glacier and can be bound by the walls of frontal and lateral moraines. These moraines, however, often are comprised of loose, unconsolidated sediment and can prove to be unstable dam structures for proglacial lakes. The factor of instability associated with the moraines poses a serious threat for failure and severe flooding. If the moraines were to be breached by the lake water, a phenomenon known as a glacial lake outburst flood (GLOF) can occur, potentially putting lives and infrastructure in harm's way. Consequently, this study examines the likelihood of a GLOF occurrence by analyzing potential trigger mechanisms associated with three proglacial lakes in the Hindu Kush Himalayan region. Using ASTER satellite imagery, one lake from Nepal, India, and Bhutan have each been assessed for possible trigger mechanisms. Our results suggest that steep-sided moraines, rugged topography, unstable masses on the upper reaches of steep slopes, and smaller lakes perched high above can all be classified as possible trigger mechanisms for the areas of study. It is imperative to be able to successfully identify potential trigger mechanisms using satellite data so that further ground observations can be made and mitigation efforts can be incorporated where needed. As lakes continue to grow, so does the cause for concern for possible GLOFs. Glacial lake outburst floods are being studied more extensively now due to the greater number of glacial lakes in high-mountainous areas. It is vitally important to understand the dynamics of a GLOF, especially the potential trigger mechanisms associated with it.

  16. Triggering extreme events at the nanoscale in photonic seas

    NASA Astrophysics Data System (ADS)

    Liu, C.; van der Wel, R. E. C.; Rotenberg, N.; Kuipers, L.; Krauss, T. F.; di Falco, A.; Fratalocchi, A.

    2015-04-01

    Hurricanes, tsunamis, rogue waves and tornadoes are rare natural phenomena that embed an exceptionally large amount of energy, which appears and quickly disappears in a probabilistic fashion. This makes them difficult to predict and hard to generate on demand. Here we demonstrate that we can trigger the onset of rare events akin to rogue waves controllably, and systematically use their generation to break the diffraction limit of light propagation. We illustrate this phenomenon in the case of a random field, where energy oscillates among incoherent degrees of freedom. Despite the low energy carried by each wave, we illustrate how to control a mechanism of spontaneous synchronization, which constructively builds up the spectral energy available in the whole bandwidth of the field into giant structures, whose statistics is predictable. The larger the frequency bandwidth of the random field, the larger the amplitude of rare events that are built up by this mechanism. Our system is composed of an integrated optical resonator, realized on a photonic crystal chip. Through near-field imaging experiments, we record confined rogue waves characterized by a spatial localization of 206 nm and with an ultrashort duration of 163 fs at a wavelength of 1.55 μm. Such localized energy patterns are formed in a deterministic dielectric structure that does not require nonlinear properties.

  17. Neural Conflict–Control Mechanisms Improve Memory for Target Stimuli

    PubMed Central

    Krebs, Ruth M.; Boehler, Carsten N.; De Belder, Maya; Egner, Tobias

    2015-01-01

    According to conflict-monitoring models, conflict serves as an internal signal for reinforcing top-down attention to task-relevant information. While evidence based on measures of ongoing task performance supports this idea, implications for long-term consequences, that is, memory, have not been tested yet. Here, we evaluated the prediction that conflict-triggered attentional enhancement of target-stimulus processing should be associated with superior subsequent memory for those stimuli. By combining functional magnetic resonance imaging (fMRI) with a novel variant of a face-word Stroop task that employed trial-unique face stimuli as targets, we were able to assess subsequent (incidental) memory for target faces as a function of whether a given face had previously been accompanied by congruent, neutral, or incongruent (conflicting) distracters. In line with our predictions, incongruent distracters not only induced behavioral conflict, but also gave rise to enhanced memory for target faces. Moreover, conflict-triggered neural activity in prefrontal and parietal regions was predictive of subsequent retrieval success, and displayed conflict-enhanced functional coupling with medial-temporal lobe regions. These data provide support for the proposal that conflict evokes enhanced top-down attention to task-relevant stimuli, thereby promoting their encoding into long-term memory. Our findings thus delineate the neural mechanisms of a novel link between cognitive control and memory. PMID:24108799

  18. Response inhibition triggered by the briefly viewed image of a hand: Behavioural and electrophysiological evidence.

    PubMed

    Vainio, L; Alén, H; Hiltunen, S; Lehikoinen, K; Lindbäck, H; Patrikainen, A; Paavilainen, P

    2013-02-01

    Previous research has shown that subliminally presented arrows produce negative priming effect in which responses are performed slower when primes and targets are calling for the same response than different response. This phenomenon has been attributed to self-inhibitory mechanisms of response processes. Similar negative priming was recently observed when participants responded to the direction of the target arrow and the prime was a briefly displayed image of a left or right hand. Responses were made slower when the left-right identity of the viewed hand was compatible with the responding hand. This was suggested to demonstrate that the proposed motor self-inhibition is a general and basic functional principle in manual control processes. However, the behavioural evidence observed in that study was not capable of showing whether the negative priming associated with a briefly displayed hand could reflect other inhibitory processes than the motor self-inhibition. The present study uses an electrophysiological indicator of automatic response priming, the lateralized readiness potential (LRP), to investigate whether the negative priming triggered by the identity of the viewed hand does indeed reflect motor self-inhibition processes. The LRP revealed a pattern of motor activation that was in line with the motor self-inhibition hypothesis. Thus, the finding supports the view that the self-inhibition mechanisms are not restricted to arrow stimuli that are presented subliminally. Rather, they are general sensorimotor mechanisms that operate in planning and control of manual actions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Toughening Mechanisms in Nanolayered MAX Phase Ceramics—A Review

    PubMed Central

    Chen, Xinhua; Bei, Guoping

    2017-01-01

    Advanced engineering and functional ceramics are sensitive to damage cracks, which delay the wide applications of these materials in various fields. Ceramic composites with enhanced fracture toughness may trigger a paradigm for design and application of the brittle components. This paper reviews the toughening mechanisms for the nanolayered MAX phase ceramics. The main toughening mechanisms for these ternary compounds were controlled by particle toughening, phase-transformation toughening and fiber-reinforced toughening, as well as texture toughening. Based on the various toughening mechanisms in MAX phase, models of SiC particles and fibers toughening Ti3SiC2 are established to predict and explain the toughening mechanisms. The modeling work provides insights and guidance to fabricate MAX phase-related composites with optimized microstructures in order to achieve the desired mechanical properties required for harsh application environments. PMID:28772723

  20. Herpes Simplex Virus Type 1 Neuronal Infection Perturbs Golgi Apparatus Integrity through Activation of Src Tyrosine Kinase and Dyn-2 GTPase

    PubMed Central

    Martin, Carolina; Leyton, Luis; Hott, Melissa; Arancibia, Yennyfer; Spichiger, Carlos; McNiven, Mark A.; Court, Felipe A.; Concha, Margarita I.; Burgos, Patricia V.; Otth, Carola

    2017-01-01

    Herpes simplex virus type 1 (HSV-1) is a ubiquitous pathogen that establishes a latent persistent neuronal infection in humans. The pathogenic effects of repeated viral reactivation in infected neurons are still unknown. Several studies have reported that during HSV-1 epithelial infection, the virus could modulate diverse cell signaling pathways remodeling the Golgi apparatus (GA) membranes, but the molecular mechanisms implicated, and the functional consequences to neurons is currently unknown. Here we report that infection of primary neuronal cultures with HSV-1 triggers Src tyrosine kinase activation and subsequent phosphorylation of Dynamin 2 GTPase, two players with a role in GA integrity maintenance. Immunofluorescence analyses showed that HSV-1 productive neuronal infection caused a scattered and fragmented distribution of the GA through the cytoplasm, contrasting with the uniform perinuclear distribution pattern observed in control cells. In addition, transmission electron microscopy revealed swollen cisternae and disorganized stacks in HSV-1 infected neurons compared to control cells. Interestingly, PP2, a selective inhibitor for Src-family kinases markedly reduced these morphological alterations of the GA induced by HSV-1 infection strongly supporting the possible involvement of Src tyrosine kinase. Finally, we showed that HSV-1 tegument protein VP11/12 is necessary but not sufficient to induce Dyn2 phosphorylation. Altogether, these results show that HSV-1 neuronal infection triggers activation of Src tyrosine kinase, phosphorylation of Dynamin 2 GTPase, and perturbation of GA integrity. These findings suggest a possible neuropathogenic mechanism triggered by HSV-1 infection, which could involve dysfunction of the secretory system in neurons and central nervous system. PMID:28879169

  1. Herpes Simplex Virus Type 1 Neuronal Infection Perturbs Golgi Apparatus Integrity through Activation of Src Tyrosine Kinase and Dyn-2 GTPase.

    PubMed

    Martin, Carolina; Leyton, Luis; Hott, Melissa; Arancibia, Yennyfer; Spichiger, Carlos; McNiven, Mark A; Court, Felipe A; Concha, Margarita I; Burgos, Patricia V; Otth, Carola

    2017-01-01

    Herpes simplex virus type 1 (HSV-1) is a ubiquitous pathogen that establishes a latent persistent neuronal infection in humans. The pathogenic effects of repeated viral reactivation in infected neurons are still unknown. Several studies have reported that during HSV-1 epithelial infection, the virus could modulate diverse cell signaling pathways remodeling the Golgi apparatus (GA) membranes, but the molecular mechanisms implicated, and the functional consequences to neurons is currently unknown. Here we report that infection of primary neuronal cultures with HSV-1 triggers Src tyrosine kinase activation and subsequent phosphorylation of Dynamin 2 GTPase, two players with a role in GA integrity maintenance. Immunofluorescence analyses showed that HSV-1 productive neuronal infection caused a scattered and fragmented distribution of the GA through the cytoplasm, contrasting with the uniform perinuclear distribution pattern observed in control cells. In addition, transmission electron microscopy revealed swollen cisternae and disorganized stacks in HSV-1 infected neurons compared to control cells. Interestingly, PP2, a selective inhibitor for Src-family kinases markedly reduced these morphological alterations of the GA induced by HSV-1 infection strongly supporting the possible involvement of Src tyrosine kinase. Finally, we showed that HSV-1 tegument protein VP11/12 is necessary but not sufficient to induce Dyn2 phosphorylation. Altogether, these results show that HSV-1 neuronal infection triggers activation of Src tyrosine kinase, phosphorylation of Dynamin 2 GTPase, and perturbation of GA integrity. These findings suggest a possible neuropathogenic mechanism triggered by HSV-1 infection, which could involve dysfunction of the secretory system in neurons and central nervous system.

  2. Mechanisms driving the lactate switch in Chinese hamster ovary cells.

    PubMed

    Hartley, Fiona; Walker, Tracy; Chung, Vicky; Morten, Karl

    2018-03-31

    The metabolism of Chinese Hamster Ovary (CHO) cells in a production environment has been extensively investigated. However, a key metabolic transition, the switch from lactate production to lactate consumption, remains enigmatic. Though commonly observed in CHO cultures, the mechanism(s) by which this metabolic shift is triggered is unknown. Despite this, efforts to control the switch have emerged due to the association of lactate consumption with improved cell growth and productivity. This review aims to consolidate current theories surrounding the lactate switch. The influence of pH, NAD + /NADH, pyruvate availability and mitochondrial function on lactate consumption are explored. A hypothesis based on the cellular redox state is put forward to explain the onset of lactate consumption. Various techniques implemented to control the lactate switch, including manipulation of the culture environment, genetic engineering, and cell line selection are also discussed. © 2018 Wiley Periodicals, Inc.

  3. Multi-Wavelength Study of Jets in Coronal Holes

    NASA Astrophysics Data System (ADS)

    Perez, Karen Isabel; Adams, Mitzi

    2018-01-01

    Jets are ejections of plasma that occur in the sun’s atmosphere, and they are small in the sun’s coronal holes. Our study focuses on jets that appear in coronal holes close to the disk center to avoid projection effects in the line-of –sight component of the magnetic field. We seek to investigate the mechanism triggering the jets, which at the time is thought to be more often flux cancellation than flux emergence. We will do this by using 94 Å, 193 Å, and 304 Å data from the Atmospheric Imaging Assembly (AIA) and magnetic field data from the Helioseismic and Magnetic Imager (HMI) of the Solar Dynamics Observatory (SDO). By analyzing a total of three jets, one from 2011 closer to solar maximum and two recent jets in May 2017 approaching the solar minimum in the three different wavelengths mentioned above and their magnetograms, we are able to compare the new and old data, as well as look at the differences found between the two extremes, leading the way to answering the question of the triggering mechanism of these on-disk coronal hole jets. After examination of the three jets, we conclude that two of them are triggered by flux cancellation, whereas the other is triggered by flux emergence. We conclude that there is not a dominant triggering mechanism and that more work must be done on these jets, as well as on a larger sample of jets, in order to come to a more concrete understanding as to what the most frequent triggering mechanism is for jets in coronal holes.

  4. Emotion triggers executive attention: anterior cingulate cortex and amygdala responses to emotional words in a conflict task.

    PubMed

    Kanske, Philipp; Kotz, Sonja A

    2011-02-01

    Coherent behavior depends on attentional control that detects and resolves conflict between opposing actions. The current functional magnetic resonance imaging study tested the hypothesis that emotion triggers attentional control to speed up conflict processing in particularly salient situations. Therefore, we presented emotionally negative and neutral words in a version of the flanker task. In response to conflict, we found activation of the dorsal anterior cingulate cortex (ACC) and of the amygdala for emotional stimuli. When emotion and conflict coincided, a region in the ventral ACC was activated, which resulted in faster conflict processing in reaction times. Emotion also increased functional connectivity between the ventral ACC and activation of the dorsal ACC and the amygdala in conflict trials. These data suggest that the ventral ACC integrates emotion and conflict and prioritizes the processing of conflict in emotional trials. This adaptive mechanism ensures rapid detection and resolution of conflict in potentially threatening situations signaled by emotional stimuli. Copyright © 2010 Wiley-Liss, Inc.

  5. A sex-inducing pheromone triggers cell cycle arrest and mate attraction in the diatom Seminavis robusta

    PubMed Central

    Moeys, Sara; Frenkel, Johannes; Lembke, Christine; Gillard, Jeroen T. F.; Devos, Valerie; Van den Berge, Koen; Bouillon, Barbara; Huysman, Marie J. J.; De Decker, Sam; Scharf, Julia; Bones, Atle; Brembu, Tore; Winge, Per; Sabbe, Koen; Vuylsteke, Marnik; Clement, Lieven; De Veylder, Lieven; Pohnert, Georg; Vyverman, Wim

    2016-01-01

    Although sexual reproduction is believed to play a major role in the high diversification rates and species richness of diatoms, a mechanistic understanding of diatom life cycle control is virtually lacking. Diatom sexual signalling is controlled by a complex, yet largely unknown, pheromone system. Here, a sex-inducing pheromone (SIP+) of the benthic pennate diatom Seminavis robusta was identified by comparative metabolomics, subsequently purified, and physicochemically characterized. Transcriptome analysis revealed that SIP+ triggers the switch from mitosis-to-meiosis in the opposing mating type, coupled with the transcriptional induction of proline biosynthesis genes, and the release of the proline-derived attraction pheromone. The induction of cell cycle arrest by a pheromone, chemically distinct from the one used to attract the opposite mating type, highlights the existence of a sophisticated mechanism to increase chances of mate finding, while keeping the metabolic losses associated with the release of an attraction pheromone to a minimum. PMID:26786712

  6. MOF Acetyl Transferase Regulates Transcription and Respiration in Mitochondria.

    PubMed

    Chatterjee, Aindrila; Seyfferth, Janine; Lucci, Jacopo; Gilsbach, Ralf; Preissl, Sebastian; Böttinger, Lena; Mårtensson, Christoph U; Panhale, Amol; Stehle, Thomas; Kretz, Oliver; Sahyoun, Abdullah H; Avilov, Sergiy; Eimer, Stefan; Hein, Lutz; Pfanner, Nikolaus; Becker, Thomas; Akhtar, Asifa

    2016-10-20

    A functional crosstalk between epigenetic regulators and metabolic control could provide a mechanism to adapt cellular responses to environmental cues. We report that the well-known nuclear MYST family acetyl transferase MOF and a subset of its non-specific lethal complex partners reside in mitochondria. MOF regulates oxidative phosphorylation by controlling expression of respiratory genes from both nuclear and mtDNA in aerobically respiring cells. MOF binds mtDNA, and this binding is dependent on KANSL3. The mitochondrial pool of MOF, but not a catalytically deficient mutant, rescues respiratory and mtDNA transcriptional defects triggered by the absence of MOF. Mof conditional knockout has catastrophic consequences for tissues with high-energy consumption, triggering hypertrophic cardiomyopathy and cardiac failure in murine hearts; cardiomyocytes show severe mitochondrial degeneration and deregulation of mitochondrial nutrient metabolism and oxidative phosphorylation pathways. Thus, MOF is a dual-transcriptional regulator of nuclear and mitochondrial genomes connecting epigenetics and metabolism. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Light driven optofluidic switch developed in a ZnO-overlaid microstructured optical fiber.

    PubMed

    Konidakis, Ioannis; Konstantaki, Maria; Tsibidis, George D; Pissadakis, Stavros

    2015-11-30

    A great challenge of Optofluidics remains the control of the fluidic properties of a photonic circuit by solely utilizing light. In this study, the development of a ZnO nanolayered microstructured optical fiber (MOF) Fabry-Perot interferometer is demonstrated, along with its fully reversible optofluidic switching behaviour. The actuation and switching principle is entirely based on the employment of light sources, i.e. UV 248 nm and green 532 nm lasers, while using modest irradiation doses. The synthesized ZnO within the MOF capillaries acts as a light triggered wettability transducer, allowing the controlled water filling and draining of the MOF Fabry-Perot cavity. The progression of the optofluidic cycle is monitored in situ with optical microscopy, while Fabry-Perot reflection spectra are monitored in real time to probe temporal infiltration behaviour. Finally, a first insight on the light triggered switching mechanism, employing photoluminescence and spectrophotometric measurements is presented. Results appear highly promising towards the design of smart in-fiber optofluidic light switching devices, suitable for actuating and sensing applications.

  8. Unraveling a Three-Step Spatiotemporal Mechanism of Triggering of Receptor-Induced Nipah Virus Fusion and Cell Entry

    PubMed Central

    Liu, Qian; Stone, Jacquelyn A.; Bradel-Tretheway, Birgit; Dabundo, Jeffrey; Benavides Montano, Javier A.; Santos-Montanez, Jennifer; Biering, Scott B.; Nicola, Anthony V.; Iorio, Ronald M.; Lu, Xiaonan; Aguilar, Hector C.

    2013-01-01

    Membrane fusion is essential for entry of the biomedically-important paramyxoviruses into their host cells (viral-cell fusion), and for syncytia formation (cell-cell fusion), often induced by paramyxoviral infections [e.g. those of the deadly Nipah virus (NiV)]. For most paramyxoviruses, membrane fusion requires two viral glycoproteins. Upon receptor binding, the attachment glycoprotein (HN/H/G) triggers the fusion glycoprotein (F) to undergo conformational changes that merge viral and/or cell membranes. However, a significant knowledge gap remains on how HN/H/G couples cell receptor binding to F-triggering. Via interdisciplinary approaches we report the first comprehensive mechanism of NiV membrane fusion triggering, involving three spatiotemporally sequential cell receptor-induced conformational steps in NiV-G: two in the head and one in the stalk. Interestingly, a headless NiV-G mutant was able to trigger NiV-F, and the two head conformational steps were required for the exposure of the stalk domain. Moreover, the headless NiV-G prematurely triggered NiV-F on virions, indicating that the NiV-G head prevents premature triggering of NiV-F on virions by concealing a F-triggering stalk domain until the correct time and place: receptor-binding. Based on these and recent paramyxovirus findings, we present a comprehensive and fundamentally conserved mechanistic model of paramyxovirus membrane fusion triggering and cell entry. PMID:24278018

  9. Numerical investigations of triggering mechanisms of shallow landslides due to heterogeneous spatio-temporal hydrological patterns.

    NASA Astrophysics Data System (ADS)

    Schwarz, Massimiliano; Cohen, Denis

    2016-04-01

    Rainfall is one of the major triggering factor of shallow landslide around the world. The increase of soil moisture in the soil influences the stability of a slope through the increase of soil bulk density, the reduction of soil apparent cohesion (due to suction stress), and the increase in pore water pressure.The spatio-temporal transformations of such properties of soil are know to be heterogeneous and under constant change. For instance, there may be a condition where, in cracked clay-soil, water, during a rain event, produces a rapid increase of pore water pressure along preferential flow-paths (crack or roots), while soil moisture and suction within the soil matrix change minimally. An another site in a sandy soil, the situation might be very different where the increase of soil moisture and pore water pressure, and the decrease of soil suction take place more or less simultaneously across the entire soil profile. In both of these cases topography plays a major role in determining the accumulation of water along the slope through different subsurface flows intensities and directions. In many documented cases in the Alps, shallow landslides may also be triggered by the punctual exfiltration of water from bedrock or weathered geological strata. The hydro-geological characteristics of the catchment control this mechanism. These different situations aim to give an idea of the large spectrum of hydrological triggering conditions of shallow landslides. The heterogeneities of these hydrological conditions represent a difficult issue in modeling shallow landslide triggering mechanisms. In the simplest models, hydrology is assumed to influence changes in pore water pressure only, mostly using one dimensional vertical infiltration models. More advanced models consider changes in apparent cohesion due to changes in soil moisture or include more complex hydrological models to simulate water flow and distribution during a rainfall event. However, most models at the regional scale rely on the infinite slope assumption for stability calculations and on continuous hydrological properties of the soil. The objective of the present study is to investigate the influence of non-continuos hydrological features (such as ephemeral springs) on the triggering mechanisms of shallow landslides using a discrete element model (SOSlope) in which the stress-strain behavior of soil is explicitly considered. The application of a stress-strain calculation allows for the simulation of local versus global loading due to hydrological processes. In particular, this study investigates the effects of different types of hydrological loading on the force redistribution on a slope associated with local displacements and following failures of soil masses. Strength and stiffness of soil are considered heterogeneous and are calculated based on the assumption of root distributions within a forested hillslope.

  10. MiR-338 controls BPA-triggered pancreatic islet insulin secretory dysfunction from compensation to decompensation by targeting Pdx-1.

    PubMed

    Wei, Jie; Ding, Dongxiao; Wang, Tao; Liu, Qiong; Lin, Yi

    2017-12-01

    Bisphenol A (BPA) can disrupt glucose homeostasis and impair pancreatic islet function; however, the mechanisms behind these effects are poorly understood. Male mice (4 wk old) were treated with BPA (50 or 500 μg/kg/d) for 8 wk. Whole-body glucose homeostasis, pancreatic islet morphology and function, and miR-338-mediated molecular signal transduction analyses were examined. We showed that BPA treatment led to a disruption of glucose tolerance and a compensatory increase of pancreatic islets insulin secretion and pancreatic and duodenal homeobox 1 ( Pdx1 ) expression in mice. Inhibition of Pdx1 reduced glucose-stimulated insulin secretion and ATP production in the islets of BPA-exposed mice. Based on primary pancreatic islets, we also confirmed that miR-338 regulated Pdx1 and thus contributed to BPA-induced insulin secretory dysfunction from compensation to decompensation. Short-term BPA exposure downregulated miR-338 through activation of G-protein-coupled estrogen receptor 1 (Gpr30), whereas long-term BPA exposure upregulated miR-338 through suppression of glucagon-like peptide 1 receptor (Glp1r). Taken together, our results reveal a molecular mechanism, whereby BPA regulates Gpr30/Glp1r to mediate the expression of miR-338, which acts to control Pdx1-dependent insulin secretion. The Gpr30/Glp1r-miR-338-Pdx1 axis should be represented as a novel mechanism by which BPA induces insulin secretory dysfunction in pancreatic islets.-Wei, J., Ding, D., Wang, T., Liu, Q., Lin, Y. MiR-338 controls BPA-triggered pancreatic islet insulin secretory dysfunction from compensation to decompensation by targeting Pdx-1. © FASEB.

  11. Effectiveness of dry needling on the lower trapezius in patients with mechanical neck pain: a randomized controlled trial.

    PubMed

    Pecos-Martín, Daniel; Montañez-Aguilera, F Javier; Gallego-Izquierdo, Tomás; Urraca-Gesto, Alicia; Gómez-Conesa, Antonia; Romero-Franco, Natalia; Plaza-Manzano, Gustavo

    2015-05-01

    To evaluate the effect of dry needling into a myofascial trigger point (MTrP) in the lower trapezius muscle of patients with mechanical idiopathic neck pain. A single-center, randomized, double-blinded controlled study. Patients were recruited from the student population of a local hospital by advertisement in the university clinic from January 2010 to December 2011. Patients (N=72) with unilateral neck pain, neck pain for ≥3 months, and active trigger points in the lower trapezius muscle were randomly assigned to 1 of 2 treatment groups. All the patients completed the study. Dry needling in an MTrP in the lower trapezius muscle, or dry needling in the lower trapezius muscle but not at an MTrP. The visual analog scale (VAS), Neck Pain Questionnaire (NPQ), and pressure-pain threshold (PPT) were assessed before the intervention and 1 week and 1 month postintervention. Treatment with dry needling of the lower trapezius muscle close to the MTrP showed decreases in pain and PPT as well as an improvement in the degree of disability (P<.001) compared with the baseline and control group measurements (P<.001). The dry-needling technique performed in the MTrP showed more significant therapeutic effects (P<.001). The application of dry needling into an active MTrP of the lower trapezius muscle induces significant changes in the VAS, NPQ, and PPT levels compared with the application of dry needling in other locations of the same muscle in patients with mechanical neck pain. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  12. Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

    PubMed Central

    Renner, Brandon; Klawitter, Jelena; Goldberg, Ryan; McCullough, James W.; Ferreira, Viviana P.; Cooper, James E.; Christians, Uwe

    2013-01-01

    Defective control of the alternative pathway of complement is an important risk factor for several renal diseases, including atypical hemolytic uremic syndrome. Infections, drugs, pregnancy, and hemodynamic insults can trigger episodes of atypical hemolytic uremic syndrome in susceptible patients. Although the mechanisms linking these clinical events with disease flares are unknown, recent work has revealed that each of these clinical conditions causes cells to release microparticles. We hypothesized that microparticles released from injured endothelial cells promote intrarenal complement activation. Calcineurin inhibitors cause vascular and renal injury and can trigger hemolytic uremic syndrome. Here, we show that endothelial cells exposed to cyclosporine in vitro and in vivo release microparticles that activate the alternative pathway of complement. Cyclosporine-induced microparticles caused injury to bystander endothelial cells and are associated with complement-mediated injury of the kidneys and vasculature in cyclosporine-treated mice. Cyclosporine-induced microparticles did not bind factor H, an alternative pathway regulatory protein present in plasma, explaining their complement-activating phenotype. Finally, we found that in renal transplant patients, the number of endothelial microparticles in plasma increases 2 weeks after starting tacrolimus, and treatment with tacrolimus associated with increased C3 deposition on endothelial microparticles in the plasma of some patients. These results suggest that injury-associated release of endothelial microparticles is an important mechanism by which systemic insults trigger intravascular complement activation and complement-dependent renal diseases. PMID:24092930

  13. Quivering on the brink: Common observations of turbidity current frequency and triggering in disparate settings

    NASA Astrophysics Data System (ADS)

    Clare, M. A.; Rosenberger, K. J.; Parsons, D. R.; Gales, J. A.; Gwiazda, R.; Paull, C. K.; Talling, P.; Cartigny, M.; Azpiroz, M.; Pope, E.; Hizzett, J. L.; Hughes Clarke, J. E.

    2017-12-01

    Turbidity currents pose a hazard to seafloor infrastructure, convey sediment to the deep sea, and provide nutrients to benthic communities. Despite their importance, we still know little about specifically how and when such powerful long run-out flows are triggered, and how strongly different trigger mechanisms control flow behaviour. New advances in direct monitoring now allow us to precisely constrain turbidity current frequency and test the efficiency of previously hypothesised triggering mechanisms. Here, we document the timing of sub-annual turbidity currents based on direct measurements using Acoustic Doppler Current Profilers at four different sites. Two sites are located at offshore fjord-head deltas in British Columbia (Squamish delta & Bute Inlet), which are fed by meltwater in spring and summer. The third is the deep-water Congo Canyon, which is located offshore Angola, and is fed by the second largest river in the world. Fourth is the Monterey Canyon, offshore California, which does not have a direct link to a river and is instead fed by littoral drift. Despite the differences in scale and setting, all of the sites show similar trends in turbidity current frequency. The first commonality is that flow timing is typically delayed (hours to weeks) following periods of rapid sediment discharge, rather than immediately coincident with them. The second commonality is that flows are rare (typically they do not occur at all) for at least half of the year in each of the sites. Instead, flows are clustered within a specific time window. We underline the importance of preconditioning prior to, and during that time window and propose that an environmental threshold must be exceeded in order to "switch on" these systems. This threshold primarily relates to magnitude of sediment delivery at the head of the channel or canyon. Once that threshold is surpassed, then systems are primed for action, quivering on the brink, allowing even small external perturbations to trigger flows.

  14. Probiotic Bacteria Induce a ‘Glow of Health’

    PubMed Central

    Smillie, Christopher; Varian, Bernard J.; Ibrahim, Yassin M.; Lakritz, Jessica R.; Alm, Eric J.; Erdman, Susan E.

    2013-01-01

    Radiant skin and hair are universally recognized as indications of good health. However, this ‘glow of health’ display remains poorly understood. We found that feeding of probiotic bacteria to aged mice induced integumentary changes mimicking peak health and reproductive fitness characteristic of much younger animals. Eating probiotic yogurt triggered epithelial follicular anagen-phase shift with sebocytogenesis resulting in thick lustrous fur due to a bacteria-triggered interleukin-10-dependent mechanism. Aged male animals eating probiotics exhibited increased subcuticular folliculogenesis, when compared with matched controls, yielding luxuriant fur only in probiotic-fed subjects. Female animals displayed probiotic-induced hyperacidity coinciding with shinier hair, a feature that also aligns with fertility in human females. Together these data provide insights into mammalian evolution and novel strategies for integumentary health. PMID:23342023

  15. Modification of Silicone Elastomer Surfaces with Zwitterionic Polymers: Short-Term Fouling Resistance and Triggered Biofouling Release.

    PubMed

    Shivapooja, Phanindhar; Yu, Qian; Orihuela, Beatriz; Mays, Robin; Rittschof, Daniel; Genzer, Jan; López, Gabriel P

    2015-11-25

    We present a method for dual-mode-management of biofouling by modifying surface of silicone elastomers with zwitterionic polymeric grafts. Poly(sulfobetaine methacrylate) was grafted from poly(vinylmethylsiloxane) elastomer substrates using thiol-ene click chemistry and surface-initiated, controlled radical polymerization. These surfaces exhibited both fouling resistance and triggered fouling-release functionality. The zwitterionic polymers exhibited fouling resistance over short-term (∼hours) exposure to bacteria and barnacle cyprids. The biofilms that eventually accumulated over prolonged-exposure (∼days) were easily detached by applying mechanical strain to the elastomer substrate. Such dual-functional surfaces may be useful in developing environmentally and biologically friendly coatings for biofouling management on marine, industrial, and biomedical equipment because they can obviate the use of toxic compounds.

  16. REM sleep-like episodes of motoneuronal depression and respiratory rate increase are triggered by pontine carbachol microinjections in in situ perfused rat brainstem preparation.

    PubMed

    Brandes, Ivo F; Stettner, Georg M; Mörschel, Michael; Kubin, Leszek; Dutschmann, Mathias

    2011-05-01

    Hypoglossal nerve activity (HNA) controls the position and movements of the tongue. In persons with compromised upper airway anatomy, sleep-related hypotonia of the tongue and other pharyngeal muscles causes increased upper airway resistance, or total upper airway obstructions, thus disrupting both sleep and breathing. Hypoglossal nerve activity reaches its nadir, and obstructive episodes are longest and most severe, during rapid eye movement stage of sleep (REMS). Microinjections of a cholinergic agonist, carbachol, into the pons have been used in vivo to investigate the mechanisms of respiratory control during REMS. Here, we recorded inspiratory-modulated phrenic nerve activity and HNA and microinjected carbachol (25-50 nl, 10 mm) into the pons in an in situ perfused working heart-brainstem rat preparation (WHBP), an ex vivo model previously validated for studies of the chemical and reflex control of breathing. Carbachol microinjections were made into 40 sites in 33 juvenile rat preparations and, at 24 sites, they triggered depression of HNA with increased respiratory rate and little change of phrenic nerve activity, a pattern akin to that during natural REMS in vivo. The REMS-like episodes started 151 ± 73 s (SD) following microinjections, lasted 20.3 ± 4.5 min, were elicited most effectively from the dorsal part of the rostral nucleus pontis oralis, and were prevented by perfusion of the preparation with atropine. The WHBP offers a novel model with which to investigate cellular and neurochemical mechanisms of REMS-related upper airway hypotonia in situ without anaesthesia and with full control over the cellular environment.

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

    PubMed

    Zhang, Xian-Ming; Han, Qing-Long

    2016-12-01

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

  18. From prediction error to incentive salience: mesolimbic computation of reward motivation

    PubMed Central

    Berridge, Kent C.

    2011-01-01

    Reward contains separable psychological components of learning, incentive motivation and pleasure. Most computational models have focused only on the learning component of reward, but the motivational component is equally important in reward circuitry, and even more directly controls behavior. Modeling the motivational component requires recognition of additional control factors besides learning. Here I will discuss how mesocorticolimbic mechanisms generate the motivation component of incentive salience. Incentive salience takes Pavlovian learning and memory as one input and as an equally important input takes neurobiological state factors (e.g., drug states, appetite states, satiety states) that can vary independently of learning. Neurobiological state changes can produce unlearned fluctuations or even reversals in the ability of a previously-learned reward cue to trigger motivation. Such fluctuations in cue-triggered motivation can dramatically depart from all previously learned values about the associated reward outcome. Thus a consequence of the difference between incentive salience and learning can be to decouple cue-triggered motivation of the moment from previously learned values of how good the associated reward has been in the past. Another consequence can be to produce irrationally strong motivation urges that are not justified by any memories of previous reward values (and without distorting associative predictions of future reward value). Such irrationally strong motivation may be especially problematic in addiction. To comprehend these phenomena, future models of mesocorticolimbic reward function should address the neurobiological state factors that participate to control generation of incentive salience. PMID:22487042

  19. Modeling CICR in rat ventricular myocytes: voltage clamp studies

    PubMed Central

    2010-01-01

    Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR) in cardiac myocytes, with voltage clamp (VC) studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR), and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+]myo). Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU), in which resides the mechanistic basis of CICR). The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel). It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+]myo. Results Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+]myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its refractory characteristics mediated by the luminal SR Ca2+ sensor. Proper functioning of the DCU, sodium-calcium exchangers and SERCA pump are important in achieving negative feedback control and hence Ca2+ homeostasis. Conclusions We examine the role of the above Ca2+ regulating mechanisms in handling various types of induced disturbances in Ca2+ levels by quantifying cellular Ca2+ balance. Our model provides biophysically-based explanations of phenomena associated with CICR generating useful and testable hypotheses. PMID:21062495

  20. The Relevance of Emotion Regulation in Explaining Why Social Exclusion Triggers Paranoia in Individuals at Clinical High Risk of Psychosis.

    PubMed

    Lincoln, Tania M; Sundag, Johanna; Schlier, Björn; Karow, Anne

    2018-06-06

    Vulnerability-stress models postulate that social stress triggers psychotic episodes in vulnerable individuals. However, experimental evidence for the proposed causal pathway is scarce and the translating mechanisms are insufficiently understood. The study assessed the impact of social exclusion on paranoid beliefs in a quasi-experimental design and investigated the role of emotion regulation (ER) as a vulnerability indicator and emotional responses as a putative translating mechanism. Participants fulfilling criteria for clinical high risk of psychosis (CHR, n = 25), controls with anxiety disorders (AC, n = 40), and healthy controls (HC, n = 40) were assessed for dysfunctional (eg, rumination, catastrophizing, blaming) and functional ER-strategies (eg, reappraising, accepting, refocusing). They were then exposed to social exclusion during a virtual ball game (Cyberball) and assessed for changes in self-reported emotions and paranoid beliefs. The CHR sample showed a significantly stronger increase in paranoid beliefs from before to after the social exclusion than both control groups. This was accounted for by lower levels of functional and higher levels of dysfunctional ER (compared to HC) and by a stronger increase in self-reported negative emotion in the CHR group (compared to AC and HC). The results confirm the role of negative emotion on the pathway from social stressors to psychotic symptoms and indicate that both the use of dysfunctional ER strategies and difficulties in employing functional strategies add to explaining why people at risk of psychosis respond to a social stressor with increased paranoia.

  1. The effects of stress and affiliation on social decision-making: Investigating the tend-and-befriend pattern.

    PubMed

    Steinbeis, Nikolaus; Engert, Veronika; Linz, Roman; Singer, Tania

    2015-12-01

    The prevalence of psychosocial stress in Western societies is constantly on the rise. Its influence on social decision-making, however, remains poorly understood. Whereas, it is known that stress triggers psychological and physiological defense mechanisms, indications of such patterns in social decisions are ambivalent. We sought to elucidate the underlying mechanisms of stress-induced social decisions. We recruited 145 men, who were individually exposed to either a psychosocial stressor or a control condition, while primed with affiliation by interacting either with members of an in- or an out-group. We found that stressed participants were less trusting and engaged in less costly punishment compared to the non-stressed control group. Interacting with out-group members led to less reciprocity and more spiteful punishment. There was no interaction between stress and the affiliation conditions in any of the used social-decision-making paradigms. Lastly, while stress-reactive cortisol levels had no effect on trust behavior, higher baseline cortisol was correlated with greater trust. Our findings suggest that previous ambiguities in data reported on the influence of stress on social decisions, namely tend-and-befriend behavior may have arisen through critical social confounds in the induction of stress. When controlling for potential social confounds, stress may trigger fight-or-flight behavior as indicated by increased social anxiety. These findings highlight the considerable context-dependence of psychosocial stress and its effects on social behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. The redshift evolution of major merger triggering of luminous AGNs: a slight enhancement at z ˜ 2

    NASA Astrophysics Data System (ADS)

    Hewlett, Timothy; Villforth, Carolin; Wild, Vivienne; Mendez-Abreu, Jairo; Pawlik, Milena; Rowlands, Kate

    2017-09-01

    Active galactic nuclei (AGNs), particularly the most luminous AGNs, are commonly assumed to be triggered through major mergers; however, observational evidence for this scenario is mixed. To investigate any influence of galaxy mergers on AGN triggering and luminosities through cosmic time, we present a sample of 106 luminous X-ray-selected type 1 AGNs from the COSMOS survey. These AGNs occupy a large redshift range (0.5 < z < 2.2) and two orders of magnitude in X-ray luminosity (˜1043-1045 erg s-1). AGN hosts are carefully mass and redshift matched to 486 control galaxies. A novel technique for identifying and quantifying merger features in galaxies is developed, subtracting galfit galaxy models and quantifying the residuals. Comparison to visual classification confirms this measure reliably picks out disturbance features in galaxies. No enhancement of merger features with increasing AGN luminosity is found with this metric, or by visual inspection. We analyse the redshift evolution of AGNs associated with galaxy mergers and find no merger enhancement in lower redshift bins. Contrarily, in the highest redshift bin (z ˜ 2) AGNs are ˜4 times more likely to be in galaxies exhibiting evidence of morphological disturbance compared to control galaxies, at 99 per cent confidence level (˜2.4σ) from visual inspection. Since only ˜15 per cent of these AGNs are found to be in morphologically disturbed galaxies, it is implied that major mergers at high redshift make a noticeable but subdominant contribution to AGN fuelling. At low redshifts, other processes dominate and mergers become a less significant triggering mechanism.

  3. Production of interleukin-1alpha by human endometrial stromal cells is triggered during menses and dysfunctional bleeding and is induced in culture by epithelial interleukin-1alpha released upon ovarian steroids withdrawal.

    PubMed

    Pretto, Chrystel M; Gaide Chevronnay, Héloïse P; Cornet, Patricia B; Galant, Christine; Delvaux, Denis; Courtoy, Pierre J; Marbaix, Etienne; Henriet, Patrick

    2008-10-01

    Endometrial breakdown during menstruation and dysfunctional bleeding is triggered by the abrupt expression of matrix metalloproteinases (MMPs), including interstitial collagenase (MMP-1). The paracrine induction of MMP-1 in stromal cells via epithelium-derived IL-1alpha is repressed by ovarian steroids. However, the control by estradiol (E) and progesterone (P) of endometrial IL-1alpha expression and bioactivity remains unknown. Variations of endometrial IL-1alpha mRNA and protein along the menstrual cycle and during dysfunctional bleeding were determined using RT-PCR, in situ hybridization, and immunolabeling. The mechanism of EP control was analyzed using culture of explants, laser capture microdissection, and purified cells. Data were compared with expression changes of IL-1beta and IL-1 receptor antagonist. IL-1alpha is synthesized by epithelial cells throughout the cycle but E and/or P prevents its release. In contrast, endometrial stromal cells produce IL-1alpha only at menses and during irregular bleeding in areas of tissue breakdown. Stromal expression of IL-1alpha, like that of MMP-1, is repressed by P (alone or with E) but triggered by epithelium-derived IL-1alpha released upon EP withdrawal. Our experiments in cultured endometrium suggest that IL-1alpha released by epithelial cells triggers the production of IL-1alpha by stromal cells in a paracrine amplification loop to induce MMP-1 expression during menstruation and dysfunctional bleeding. All three steps of this amplification cascade are repressed by EP.

  4. A Strategy for a Parametric Flood Insurance Using Proxies

    NASA Astrophysics Data System (ADS)

    Haraguchi, M.; Lall, U.

    2017-12-01

    Traditionally, the design of flood control infrastructure and flood plain zoning require the estimation of return periods, which have been calculated by river hydraulic models with rainfall-runoff models. However, this multi-step modeling process leads to significant uncertainty to assess inundation. In addition, land use change and changing climate alter the potential losses, as well as make the modeling results obsolete. For these reasons, there is a strong need to create parametric indexes for the financial risk transfer for large flood events, to enable rapid response and recovery. Hence, this study examines the possibility of developing a parametric flood index at the national or regional level in Asia, which can be quickly mobilized after catastrophic floods. Specifically, we compare a single trigger based on rainfall index with multiple triggers using rainfall and streamflow indices by conducting case studies in Bangladesh and Thailand. The proposed methodology is 1) selecting suitable indices of rainfall and streamflow (if available), 2) identifying trigger levels for specified return periods for losses using stepwise and logistic regressions, 3) measuring the performance of indices, and 4) deriving return periods of selected windows and trigger levels. Based on the methodology, actual trigger levels were identified for Bangladesh and Thailand. Models based on multiple triggers reduced basis risks, an inherent problem in an index insurance. The proposed parametric flood index can be applied to countries with similar geographic and meteorological characteristics, and serve as a promising method for ex-ante risk financing for developing countries. This work is intended to be a preliminary work supporting future work on pricing risk transfer mechanisms in ex-ante risk finance.

  5. Effects of hydromechanical loading history and antecedent soil mechanical damage on shallow landslide triggering

    NASA Astrophysics Data System (ADS)

    Fan, Linfeng; Lehmann, Peter; Or, Dani

    2015-10-01

    Evidence suggests that the sudden triggering of rainfall-induced shallow landslides is preceded by accumulation of local internal failures in the soil mantle before their abrupt coalescence into a landslide failure plane. The mechanical status of a hillslope at any given time reflects competition between local damage accumulated during antecedent rainfall events and rates of mechanical healing (e.g., rebonding of microcracks and root regrowth). This dynamic interplay between damage accumulation and healing rates determines the initial mechanical state for landslide modeling. We evaluated the roles of these dynamic processes on landslide characteristics and patterns using a hydromechanical landslide-triggering model for a sequence of rainfall scenarios. The progressive nature of soil failure was represented by the fiber bundle model formalism that considers threshold strength of mechanical bonds linking adjacent soil columns and bedrock. The antecedent damage induced by prior rainfall events was expressed by the fraction of broken fibers that gradually regain strength or mechanically heal at rates specific to soil and roots. Results indicate that antecedent damage accelerates landslide initiation relative to pristine (undamaged) hillslopes. The volumes of first triggered landslides increase with increasing antecedent damage; however, for heavily damaged hillslopes, landslide volumes tend to decrease. Elapsed time between rainfall events allows mechanical healing that reduces the effects of antecedent damage. This study proposed a quantitative framework for systematically incorporating hydromechanical loading history and information on precursor events (e.g., such as recorded by acoustic emissions) into shallow landslide hazard assessment.

  6. Superconducting matrix fault current limiter with current-driven trigger mechanism

    DOEpatents

    Yuan; Xing

    2008-04-15

    A modular and scalable Matrix-type Fault Current Limiter (MFCL) that functions as a "variable impedance" device in an electric power network, using components made of superconducting and non-superconducting electrically conductive materials. An inductor is connected in series with the trigger superconductor in the trigger matrix and physically surrounds the superconductor. The current surge during a fault will generate a trigger magnetic field in the series inductor to cause fast and uniform quenching of the trigger superconductor to significantly reduce burnout risk due to superconductor material non-uniformity.

  7. WebBee: A Platform for Secure Coordination and Communication in Crisis Scenarios

    DTIC Science & Technology

    2008-04-16

    implemented through database triggers. The Webbee Database Server contains an Information Server, which is a Postgres database with PostGIS [5] extension...sends it to the target user. The heavy lifting for this mechanism is done through an extension of Postgres triggers (Figures 6.1 and 6.2), resulting...in fewer queries and better performance. Trigger support in Postgres is table-based and comparatively primitive: with n table triggers, an update

  8. The Roles of the Bone Marrow Microenvironment in Controlling Tumor Dormancy

    DTIC Science & Technology

    2017-10-01

    Prostate cancer patients often have long time periods betweencurative intent surgery or radiation therapy until the time of biochemical recurrence or...incurred by the consequent excision of some benign masses. Radiation triggers EMT Above we reviewed some evidence that chemotherapy and mechanical...tissue disruption give rise to CTC and EMT in surviving cells. Below we review data showing radiation causes CTC and EMT as well.45,46 For a few specific

  9. Sterile Inflammation of Brain, due to Activation of Innate Immunity, as a Culprit in Psychiatric Disorders

    PubMed Central

    Ratajczak, Mariusz Z.; Pedziwiatr, Daniel; Cymer, Monika; Kucia, Magda; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy

    2018-01-01

    Evidence has accumulated that the occurrence of psychiatric disorders is related to chronic inflammation. In support of this linkage, changes in the levels of circulating pro-inflammatory cytokines and chemokines in the peripheral blood (PB) of psychiatric patients as well as correlations between chronic inflammatory processes and psychiatric disorders have been described. Furthermore, an inflammatory process known as “sterile inflammation” when initiated directly in brain tissue may trigger the onset of psychoses. In this review, we will present the hypothesis that prolonged or chronic activation of the complement cascade (ComC) directly triggers inflammation in the brain and affects the proper function of this organ. Based on the current literature and our own work on mechanisms activating the ComC we hypothesize that inflammation in the brain is initiated by the mannan-binding lectin pathway of ComC activation. This activation is triggered by an increase in brain tissue of danger-associated molecular pattern (DAMP) mediators, including extracellular ATP and high-mobility group box 1 (HMGB1) protein, which are recognized by circulating pattern-recognition receptors, including mannan-binding lectin (MBL), that activate the ComC. On the other hand, this process is controlled by the anti-inflammatory action of heme oxygenase 1 (HO-1). In this review, we will try to connect changes in the release of DAMPs in the brain with inflammatory processes triggered by the innate immunity involving activation of the ComC as well as the inflammation-limiting effects of the anti-inflammatory HO-1 pathway. We will also discuss parallel observations that during ComC activation subsets of stem cells are mobilized into PB from bone marrow that are potentially involved in repair mechanisms. PMID:29541038

  10. Sterile Inflammation of Brain, due to Activation of Innate Immunity, as a Culprit in Psychiatric Disorders.

    PubMed

    Ratajczak, Mariusz Z; Pedziwiatr, Daniel; Cymer, Monika; Kucia, Magda; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy

    2018-01-01

    Evidence has accumulated that the occurrence of psychiatric disorders is related to chronic inflammation. In support of this linkage, changes in the levels of circulating pro-inflammatory cytokines and chemokines in the peripheral blood (PB) of psychiatric patients as well as correlations between chronic inflammatory processes and psychiatric disorders have been described. Furthermore, an inflammatory process known as "sterile inflammation" when initiated directly in brain tissue may trigger the onset of psychoses. In this review, we will present the hypothesis that prolonged or chronic activation of the complement cascade (ComC) directly triggers inflammation in the brain and affects the proper function of this organ. Based on the current literature and our own work on mechanisms activating the ComC we hypothesize that inflammation in the brain is initiated by the mannan-binding lectin pathway of ComC activation. This activation is triggered by an increase in brain tissue of danger-associated molecular pattern (DAMP) mediators, including extracellular ATP and high-mobility group box 1 (HMGB1) protein, which are recognized by circulating pattern-recognition receptors, including mannan-binding lectin (MBL), that activate the ComC. On the other hand, this process is controlled by the anti-inflammatory action of heme oxygenase 1 (HO-1). In this review, we will try to connect changes in the release of DAMPs in the brain with inflammatory processes triggered by the innate immunity involving activation of the ComC as well as the inflammation-limiting effects of the anti-inflammatory HO-1 pathway. We will also discuss parallel observations that during ComC activation subsets of stem cells are mobilized into PB from bone marrow that are potentially involved in repair mechanisms.

  11. Near Optimal Event-Triggered Control of Nonlinear Discrete-Time Systems Using Neurodynamic Programming.

    PubMed

    Sahoo, Avimanyu; Xu, Hao; Jagannathan, Sarangapani

    2016-09-01

    This paper presents an event-triggered near optimal control of uncertain nonlinear discrete-time systems. Event-driven neurodynamic programming (NDP) is utilized to design the control policy. A neural network (NN)-based identifier, with event-based state and input vectors, is utilized to learn the system dynamics. An actor-critic framework is used to learn the cost function and the optimal control input. The NN weights of the identifier, the critic, and the actor NNs are tuned aperiodically once every triggered instant. An adaptive event-trigger condition to decide the trigger instants is derived. Thus, a suitable number of events are generated to ensure a desired accuracy of approximation. A near optimal performance is achieved without using value and/or policy iterations. A detailed analysis of nontrivial inter-event times with an explicit formula to show the reduction in computation is also derived. The Lyapunov technique is used in conjunction with the event-trigger condition to guarantee the ultimate boundedness of the closed-loop system. The simulation results are included to verify the performance of the controller. The net result is the development of event-driven NDP.

  12. Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo.

    PubMed

    Barriga, Elias H; Franze, Kristian; Charras, Guillaume; Mayor, Roberto

    2018-02-22

    Collective cell migration is essential for morphogenesis, tissue remodelling and cancer invasion. In vivo, groups of cells move in an orchestrated way through tissues. This movement involves mechanical as well as molecular interactions between cells and their environment. While the role of molecular signals in collective cell migration is comparatively well understood, how tissue mechanics influence collective cell migration in vivo remains unknown. Here we investigated the importance of mechanical cues in the collective migration of the Xenopus laevis neural crest cells, an embryonic cell population whose migratory behaviour has been likened to cancer invasion. We found that, during morphogenesis, the head mesoderm underlying the cephalic neural crest stiffens. This stiffening initiates an epithelial-to-mesenchymal transition in neural crest cells and triggers their collective migration. To detect changes in their mechanical environment, neural crest cells use mechanosensation mediated by the integrin-vinculin-talin complex. By performing mechanical and molecular manipulations, we show that mesoderm stiffening is necessary and sufficient to trigger neural crest migration. Finally, we demonstrate that convergent extension of the mesoderm, which starts during gastrulation, leads to increased mesoderm stiffness by increasing the cell density underneath the neural crest. These results show that convergent extension of the mesoderm has a role as a mechanical coordinator of morphogenesis, and reveal a link between two apparently unconnected processes-gastrulation and neural crest migration-via changes in tissue mechanics. Overall, we demonstrate that changes in substrate stiffness can trigger collective cell migration by promoting epithelial-to-mesenchymal transition in vivo. More broadly, our results raise the idea that tissue mechanics combines with molecular effectors to coordinate morphogenesis.

  13. Minimization of Basis Risk in Parametric Earthquake Cat Bonds

    NASA Astrophysics Data System (ADS)

    Franco, G.

    2009-12-01

    A catastrophe -cat- bond is an instrument used by insurance and reinsurance companies, by governments or by groups of nations to cede catastrophic risk to the financial markets, which are capable of supplying cover for highly destructive events, surpassing the typical capacity of traditional reinsurance contracts. Parametric cat bonds, a specific type of cat bonds, use trigger mechanisms or indices that depend on physical event parameters published by respected third parties in order to determine whether a part or the entire bond principal is to be paid for a certain event. First generation cat bonds, or cat-in-a-box bonds, display a trigger mechanism that consists of a set of geographic zones in which certain conditions need to be met by an earthquake’s magnitude and depth in order to trigger payment of the bond principal. Second generation cat bonds use an index formulation that typically consists of a sum of products of a set of weights by a polynomial function of the ground motion variables reported by a geographically distributed seismic network. These instruments are especially appealing to developing countries with incipient insurance industries wishing to cede catastrophic losses to the financial markets because the payment trigger mechanism is transparent and does not involve the parties ceding or accepting the risk, significantly reducing moral hazard. In order to be successful in the market, however, parametric cat bonds have typically been required to specify relatively simple trigger conditions. The consequence of such simplifications is the increase of basis risk. This risk represents the possibility that the trigger mechanism fails to accurately capture the actual losses of a catastrophic event, namely that it does not trigger for a highly destructive event or vice versa, that a payment of the bond principal is caused by an event that produced insignificant losses. The first case disfavors the sponsor who was seeking cover for its losses while the second disfavors the investor who loses part of the investment without a reasonable cause. A streamlined and fairly automated methodology has been developed to design parametric triggers that minimize the basis risk while still maintaining their level of relative simplicity. Basis risk is minimized in both, first and second generation, parametric cat bonds through an optimization procedure that aims to find the most appropriate magnitude thresholds, geographic zones, and weight index values. Sensitivity analyses to different design assumptions show that first generation cat bonds are typically affected by a large negative basis risk, namely the risk that the bond will not trigger for events within the risk level transferred, unless a sufficiently small geographic resolution is selected to define the trigger zones. Second generation cat bonds in contrast display a bias towards negative or positive basis risk depending on the degree of the polynomial used as well as on other design parameters. Two examples are presented, the construction of a first generation parametric trigger mechanism for Costa Rica and the design of a second generation parametric index for Japan.

  14. Engineering responsive supramolecular biomaterials: Toward smart therapeutics.

    PubMed

    Webber, Matthew J

    2016-09-01

    Engineering materials using supramolecular principles enables generalizable and modular platforms that have tunable chemical, mechanical, and biological properties. Applying this bottom-up, molecular engineering-based approach to therapeutic design affords unmatched control of emergent properties and functionalities. In preparing responsive materials for biomedical applications, the dynamic character of typical supramolecular interactions facilitates systems that can more rapidly sense and respond to specific stimuli through a fundamental change in material properties or characteristics, as compared to cases where covalent bonds must be overcome. Several supramolecular motifs have been evaluated toward the preparation of "smart" materials capable of sensing and responding to stimuli. Triggers of interest in designing materials for therapeutic use include applied external fields, environmental changes, biological actuators, applied mechanical loading, and modulation of relative binding affinities. In addition, multistimuli-responsive routes can be realized that capture combinations of triggers for increased functionality. In sum, supramolecular engineering offers a highly functional strategy to prepare responsive materials. Future development and refinement of these approaches will improve precision in material formation and responsiveness, seek dynamic reciprocity in interactions with living biological systems, and improve spatiotemporal sensing of disease for better therapeutic deployment.

  15. Activity of (2060) Chiron possibly caused by impacts?

    NASA Astrophysics Data System (ADS)

    Cikota, Stefan; Fernández-Valenzuela, Estela; Ortiz, Jose Luis; Morales, Nicolás; Duffard, René; Aceituno, Jesus; Cikota, Aleksandar; Santos-Sanz, Pablo

    2018-04-01

    The centaur 95P/(2060) Chiron is showing comet-like activity since its discovery, but the mass-loss mechanisms triggering its activity remained unexplained. Although the collision rates in the centaur region are expected to be very low, and impacts are thought not to be responsible for the mass-loss, since the recent indications that Chiron might possess a ring similar to Chariklo's, and assuming that there is debris orbiting around, the impact triggered mass-loss mechanism should not be excluded as a possible cause of its activity. From time series observations collected on Calar Alto Observatory in Spain between 2014 and 2016, we found that the photometric scatter in Chiron's data is larger than a control star's scatter, indicating a possible microactivity, possibly caused by debris falling back to Chiron's surface and lifting small clouds of material. We also present rotational light curves, and measurements of Chiron's absolute magnitudes, which are consistent with the models supporting the presumption that Chiron possesses rings. By co-adding the images acquired in 2015, we have detected an ˜5 arcsec long tail, showing a surface brightness of 25.3 mag(V) arcsec-2.

  16. What triggers catch-up saccades during visual tracking?

    PubMed

    de Brouwer, Sophie; Yuksel, Demet; Blohm, Gunnar; Missal, Marcus; Lefèvre, Philippe

    2002-03-01

    When tracking moving visual stimuli, primates orient their visual axis by combining two kinds of eye movements, smooth pursuit and saccades, that have very different dynamics. Yet, the mechanisms that govern the decision to switch from one type of eye movement to the other are still poorly understood, even though they could bring a significant contribution to the understanding of how the CNS combines different kinds of control strategies to achieve a common motor and sensory goal. In this study, we investigated the oculomotor responses to a large range of different combinations of position error and velocity error during visual tracking of moving stimuli in humans. We found that the oculomotor system uses a prediction of the time at which the eye trajectory will cross the target, defined as the "eye crossing time" (T(XE)). The eye crossing time, which depends on both position error and velocity error, is the criterion used to switch between smooth and saccadic pursuit, i.e., to trigger catch-up saccades. On average, for T(XE) between 40 and 180 ms, no saccade is triggered and target tracking remains purely smooth. Conversely, when T(XE) becomes smaller than 40 ms or larger than 180 ms, a saccade is triggered after a short latency (around 125 ms).

  17. Mechanisms that improve referential access*

    PubMed Central

    Gernsbacher, Morton Ann

    2015-01-01

    Two mechanisms, suppression and enhancement, are proposed to improve referential access. Enhancement improves the accessibility of previously mentioned concepts by increasing or boosting their activation; suppression improves concepts’ accessibility by decreasing or dampening the activation of other concepts. Presumably, these mechanisms are triggered by the informational content of anaphors. Six experiments investigated this proposal by manipulating whether an anaphoric reference was made with a very explicit, repeated name anaphor or a less explicit pronoun. Subjects read sentences that introduced two participants in their first clauses, for example, “Ann predicted that Pam would lose the track race,” and the sentences referred to one of the two participants in their second clauses, “but Pam/she came in first very easily.” While subjects read each sentence, the activation level of the two participants was measured by a probe verification task. The first two experiments demonstrated that explicit, repeated name anaphors immediately trigger the enhancement of their own antecedents and immediately trigger the suppression of other (nonantecedent) participants. The third experiment demonstrated that less explicit, pronoun anaphors also trigger the suppression of other nonantecedents, but they do so less quickly—even when, as in the fourth experiment, the semantic information to identify their antecedents occurs prior to the pronouns (e.g., “Ann predicted that Pam would lose the track race. But after winning the race, she …”). The fifth experiment demonstrated that more explicit pronouns – pronouns that match the gender of only one participant—trigger suppression more powerfully. A final experiment demonstrated that it is not only rementioned participants who improve their referential access by triggering the suppression of other participants; newly introduced participants do so too (e.g., “Ann predicted that Pam would lose the track race, but Kim …”). Thus, both suppression and enhancement improve referential access, and the contribution of these two mechanisms is a function of explicitness. The role of these two mechanisms in mediating other referential access phenomena is also discussed. PMID:2752708

  18. Development of the sonic pump levitator

    NASA Technical Reports Server (NTRS)

    Dunn, S. A.

    1985-01-01

    The process and mechanism involved in producing glass microballoons (GMBs) of acceptable quality for laser triggered inertial fusion through use of glass jet levitation and manipulation are considered. The gas jet levitation device, called sonic pumps, provides positioning by timely and appropriate application of gas mementum from one or more of six sonic pumps which are arranged orthogonally in opposed pairs about the levitation region and are activated by an electrooptical, computer controlled, feedback system. The levitation device was fabricated and its associated control systems were assembled into a package and tested in reduced gravity flight regime of the NASA KC-135 aircraft.

  19. Rogue wave triggered at a critical frequency of a nonlinear resonant medium.

    PubMed

    He, Jingsong; Xu, Shuwei; Porsezian, K; Cheng, Yi; Dinda, P Tchofo

    2016-06-01

    We consider a two-level atomic system interacting with an electromagnetic field controlled in amplitude and frequency by a high intensity laser. We show that the amplitude of the induced electric field admits an envelope profile corresponding to a breather soliton. We demonstrate that this soliton can propagate with any frequency shift with respect to that of the control laser, except a critical frequency, at which the system undergoes a structural discontinuity that transforms the breather in a rogue wave. A mechanism of generation of rogue waves by means of an intense laser field is thus revealed.

  20. Immediate increase in food intake following exercise messages.

    PubMed

    Albarracin, Dolores; Wang, Wei; Leeper, Joshua

    2009-07-01

    Communications to stimulate weight loss include exercise-promotion messages that often produce unsatisfactory results due to compensatory behavioral and metabolic mechanisms triggered by physical activity. This research investigated potential automatic facilitation of eating immediately after exercise messages in the absence of actual exercise. Two controlled experiments demonstrated greater than control food intake following exposure to print messages typical of exercise campaigns as well as subliminal presentation of action words associated with exercise (e.g., "active"). These inadvertent effects may explain the limited efficacy of exercise-promotion programs for weight loss, particularly when systematic dietary guidelines are absent.

  1. Initiation of parturition in humans.

    PubMed

    Drover, J W; Casper, R F

    1983-02-15

    The mechanism by which parturition is initiated in humans is largely unknown. The placenta and fetal membranes appear to play the major role in the initiation of labour, and the fetus may influence the timing of labour. Clinical observations and experiments with animals have revealed that placental neuropeptides may be able to control steroid metabolism and trigger the onset of labour, while the fetus may be able to interact with such events to initiate parturition at an appropriate time. However, further study is needed to determine the role of placental releasing factors and glycoprotein hormones and their ability to control placental steroid metabolism.

  2. A Codimension-2 Bifurcation Controlling Endogenous Bursting Activity and Pulse-Triggered Responses of a Neuron Model

    PubMed Central

    Barnett, William H.; Cymbalyuk, Gennady S.

    2014-01-01

    The dynamics of individual neurons are crucial for producing functional activity in neuronal networks. An open question is how temporal characteristics can be controlled in bursting activity and in transient neuronal responses to synaptic input. Bifurcation theory provides a framework to discover generic mechanisms addressing this question. We present a family of mechanisms organized around a global codimension-2 bifurcation. The cornerstone bifurcation is located at the intersection of the border between bursting and spiking and the border between bursting and silence. These borders correspond to the blue sky catastrophe bifurcation and the saddle-node bifurcation on an invariant circle (SNIC) curves, respectively. The cornerstone bifurcation satisfies the conditions for both the blue sky catastrophe and SNIC. The burst duration and interburst interval increase as the inverse of the square root of the difference between the corresponding bifurcation parameter and its bifurcation value. For a given set of burst duration and interburst interval, one can find the parameter values supporting these temporal characteristics. The cornerstone bifurcation also determines the responses of silent and spiking neurons. In a silent neuron with parameters close to the SNIC, a pulse of current triggers a single burst. In a spiking neuron with parameters close to the blue sky catastrophe, a pulse of current temporarily silences the neuron. These responses are stereotypical: the durations of the transient intervals–the duration of the burst and the duration of latency to spiking–are governed by the inverse-square-root laws. The mechanisms described here could be used to coordinate neuromuscular control in central pattern generators. As proof of principle, we construct small networks that control metachronal-wave motor pattern exhibited in locomotion. This pattern is determined by the phase relations of bursting neurons in a simple central pattern generator modeled by a chain of oscillators. PMID:24497927

  3. Deployable robotic woven wire structures and joints for space applications

    NASA Technical Reports Server (NTRS)

    Shahinpoor, MO; Smith, Bradford

    1991-01-01

    Deployable robotic structures are basically expandable and contractable structures that may be transported or launched to space in a compact form. These structures may then be intelligently deployed by suitable actuators. The deployment may also be done by means of either airbag or spring-loaded typed mechanisms. The actuators may be pneumatic, hydraulic, ball-screw type, or electromagnetic. The means to trigger actuation may be on-board EPROMS, programmable logic controllers (PLCs) that trigger actuation based on some input caused by the placement of the structure in the space environment. The actuation may also be performed remotely by suitable remote triggering devices. Several deployable woven wire structures are examined. These woven wire structures possess a unique form of joint, the woven wire joint, which is capable of moving and changing its position and orientation with respect to the structure itself. Due to the highly dynamic and articulate nature of these joints the 3-D structures built using them are uniquely and highly expandable, deployable, and dynamic. The 3-D structure naturally gives rise to a new generation of deployable three-dimensional spatial structures.

  4. Lack of evidence of rotavirus-dependent molecular mimicry as a trigger of coeliac disease.

    PubMed

    Ziberna, F; De Lorenzo, G; Schiavon, V; Arnoldi, F; Quaglia, S; De Leo, L; Vatta, S; Martelossi, S; Burrone, O R; Ventura, A; Not, T

    2016-12-01

    New data suggest the involvement of rotavirus (RV) in triggering autoimmunity in coeliac disease (CD) by molecular mimicry between the human-transglutaminase protein and the dodecapeptide (260-271 aa) of the RV protein VP7 (pVP7). To assess the role of RV in the onset of CD, we measured anti-pVP7 antibodies in the sera of children with CD and of control groups. We analysed serum samples of 118 biopsy-proven CD patients and 46 patients with potential CD; 32 children with other gastrointestinal diseases; 107 no-CD children and 107 blood donors. Using enzyme-linked immunosorbent assay (ELISA) assay, we measured immunoglobulin (Ig)A-IgG antibodies against the synthetic peptides pVP7, the human transglutaminase-derived peptide (476-487 aa) which shows a homology with VP7 protein and a control peptide. The triple-layered RV particles (TLPs) containing the VP7 protein and the double-layered RV-particles (DLPs) lacking the VP7 protein were also used as antigens in ELISA assay. Antibody reactivity to the RV-TLPs was positive in 22 of 118 (18%) CD patients and in both paediatric (17 of 107, 16%) and adult (29 of 107, 27%) control groups, without showing a statistically significant difference among them (P = 0·6, P = 0·1). Biopsy-proven CD patients as well as the adult control group demonstrated a high positive antibody reactivity against both pVP7 (34 of 118, 29% CD patients; 66 of 107, 62% adult controls) and control synthetic peptides (35 of 118, 30% CD patients; 56 of 107, 52% adult controls), suggesting a non-specific response against RV pVP7. We show that children with CD do not have higher immune reactivity to RV, thus questioning the molecular mimicry mechanism as a triggering factor of CD. © 2016 British Society for Immunology.

  5. Effects of Spatial Variability of Soil Properties on the Triggering of Rainfall-Induced Shallow Landslides

    NASA Astrophysics Data System (ADS)

    Fan, Linfeng; Lehmann, Peter; Or, Dani

    2015-04-01

    Naturally-occurring spatial variations in soil properties (e.g., soil depth, moisture, and texture) affect key hydrological processes and potentially the mechanical response of soil to hydromechanical loading (relative to the commonly-assumed uniform soil mantle). We quantified the effects of soil spatial variability on the triggering of rainfall-induced shallow landslides at the hillslope- and catchment-scales, using a physically-based landslide triggering model that considers interacting soil columns with mechanical strength thresholds (represented by the Fiber Bundle Model). The spatial variations in soil properties are represented as Gaussian random distributions and the level of variation is characterized by the coefficient of variation and correlation lengths of soil properties (i.e., soil depth, soil texture and initial water content in this study). The impacts of these spatial variations on landslide triggering characteristics were measured by comparing the times to triggering and landslide volumes for heterogeneous soil properties and homogeneous cases. Results at hillslope scale indicate that for spatial variations of an individual property (without cross correlation), the increasing of coefficient of variation introduces weak spots where mechanical damage is accelerated and leads to earlier onset of landslide triggering and smaller volumes. Increasing spatial correlation length of soil texture and initial water content also induces early landslide triggering and small released volumes due to the transition of failure mode from brittle to ductile failure. In contrast, increasing spatial correlation length of soil depth "reduces" local steepness and postpones landslide triggering. Cross-correlated soil properties generally promote landslide initiation, but depending on the internal structure of spatial distribution of each soil property, landslide triggering may be reduced. The effects of cross-correlation between initial water content and soil texture were investigated in detail at the catchment scale by incorporating correlations of both variables with topography. Results indicate that the internal structure of the spatial distribution of each soil property together with their interplays determine the overall performance of the coupled spatial variability. This study emphasizes the importance of both the randomness and spatial structure of soil properties on landslide triggering and characteristics.

  6. Tailored Hypersound Generation in Single Plasmonic Nanoantennas.

    PubMed

    Della Picca, Fabricio; Berte, Rodrigo; Rahmani, Mohsen; Albella, Pablo; Bujjamer, Juan M; Poblet, Martín; Cortés, Emiliano; Maier, Stefan A; Bragas, Andrea V

    2016-02-10

    Ultrashort laser pulses impinging on a plasmonic nanostructure trigger a highly dynamic scenario in the interplay of electronic relaxation with lattice vibrations, which can be experimentally probed via the generation of coherent phonons. In this Letter, we present studies of hypersound generation in the range of a few to tens of gigahertz on single gold plasmonic nanoantennas, which have additionally been subjected to predesigned mechanical constraints via silica bridges. Using these hybrid gold/silica nanoantennas, we demonstrate experimentally and via numerical simulations how mechanical constraints allow control over their vibrational mode spectrum. Degenerate pump-probe techniques with double modulation are performed in order to detect the small changes produced in the probe transmission by the mechanical oscillations of these single nanoantennas.

  7. Error Recovery in the Time-Triggered Paradigm with FTT-CAN.

    PubMed

    Marques, Luis; Vasconcelos, Verónica; Pedreiras, Paulo; Almeida, Luís

    2018-01-11

    Data networks are naturally prone to interferences that can corrupt messages, leading to performance degradation or even to critical failure of the corresponding distributed system. To improve resilience of critical systems, time-triggered networks are frequently used, based on communication schedules defined at design-time. These networks offer prompt error detection, but slow error recovery that can only be compensated with bandwidth overprovisioning. On the contrary, the Flexible Time-Triggered (FTT) paradigm uses online traffic scheduling, which enables a compromise between error detection and recovery that can achieve timely recovery with a fraction of the needed bandwidth. This article presents a new method to recover transmission errors in a time-triggered Controller Area Network (CAN) network, based on the Flexible Time-Triggered paradigm, namely FTT-CAN. The method is based on using a server (traffic shaper) to regulate the retransmission of corrupted or omitted messages. We show how to design the server to simultaneously: (1) meet a predefined reliability goal, when considering worst case error recovery scenarios bounded probabilistically by a Poisson process that models the fault arrival rate; and, (2) limit the direct and indirect interference in the message set, preserving overall system schedulability. Extensive simulations with multiple scenarios, based on practical and randomly generated systems, show a reduction of two orders of magnitude in the average bandwidth taken by the proposed error recovery mechanism, when compared with traditional approaches available in the literature based on adding extra pre-defined transmission slots.

  8. Error Recovery in the Time-Triggered Paradigm with FTT-CAN

    PubMed Central

    Pedreiras, Paulo; Almeida, Luís

    2018-01-01

    Data networks are naturally prone to interferences that can corrupt messages, leading to performance degradation or even to critical failure of the corresponding distributed system. To improve resilience of critical systems, time-triggered networks are frequently used, based on communication schedules defined at design-time. These networks offer prompt error detection, but slow error recovery that can only be compensated with bandwidth overprovisioning. On the contrary, the Flexible Time-Triggered (FTT) paradigm uses online traffic scheduling, which enables a compromise between error detection and recovery that can achieve timely recovery with a fraction of the needed bandwidth. This article presents a new method to recover transmission errors in a time-triggered Controller Area Network (CAN) network, based on the Flexible Time-Triggered paradigm, namely FTT-CAN. The method is based on using a server (traffic shaper) to regulate the retransmission of corrupted or omitted messages. We show how to design the server to simultaneously: (1) meet a predefined reliability goal, when considering worst case error recovery scenarios bounded probabilistically by a Poisson process that models the fault arrival rate; and, (2) limit the direct and indirect interference in the message set, preserving overall system schedulability. Extensive simulations with multiple scenarios, based on practical and randomly generated systems, show a reduction of two orders of magnitude in the average bandwidth taken by the proposed error recovery mechanism, when compared with traditional approaches available in the literature based on adding extra pre-defined transmission slots. PMID:29324723

  9. Diet and lifestyle as trigger factors for the onset of heartburn.

    PubMed

    Oliver, Katie; Davies, Gloria; Dettmar, Peter

    To examine prospectively the role of reported trigger factors on symptom onset in patients with heartburn and highlight the role of these factors in the management of heartburn in the primary care setting. METHOD Twenty-two patients with heartburn and 50 controls were recruited in Bedfordshire, UK. A seven-day symptom and trigger diary was completed by patients and controls. Patients reported a collection of heartburn symptoms varying in severity and time of day. Aspects of diet and lifestyle perceived as trigger factors included large meals, time of eating and posture. Multiple trigger factors were reported for heartburn. Although symptom onset varies between individuals, consideration should be given to trigger factors in the management of heartburn symptoms.

  10. Mechanisms for greater insulin-stimulated glucose uptake in normal and insulin-resistant skeletal muscle after acute exercise

    PubMed Central

    2015-01-01

    Enhanced skeletal muscle and whole body insulin sensitivity can persist for up to 24–48 h after one exercise session. This review focuses on potential mechanisms for greater postexercise and insulin-stimulated glucose uptake (ISGU) by muscle in individuals with normal or reduced insulin sensitivity. A model is proposed for the processes underlying this improvement; i.e., triggers initiate events that activate subsequent memory elements, which store information that is relayed to mediators, which translate memory into action by controlling an end effector that directly executes increased insulin-stimulated glucose transport. Several candidates are potential triggers or memory elements, but none have been conclusively verified. Regarding potential mediators in both normal and insulin-resistant individuals, elevated postexercise ISGU with a physiological insulin dose coincides with greater Akt substrate of 160 kDa (AS160) phosphorylation without improved proximal insulin signaling at steps from insulin receptor binding to Akt activity. Causality remains to be established between greater AS160 phosphorylation and improved ISGU. The end effector for normal individuals is increased GLUT4 translocation, but this remains untested for insulin-resistant individuals postexercise. Following exercise, insulin-resistant individuals can attain ISGU values similar to nonexercising healthy controls, but after a comparable exercise protocol performed by both groups, ISGU for the insulin-resistant group has been consistently reported to be below postexercise values for the healthy group. Further research is required to fully understand the mechanisms underlying the improved postexercise ISGU in individuals with normal or subnormal insulin sensitivity and to explain the disparity between these groups after similar exercise. PMID:26487009

  11. Degassing during quiescence as a trigger of magma ascent and volcanic eruptions

    PubMed Central

    Girona, Társilo; Costa, Fidel; Schubert, Gerald

    2015-01-01

    Understanding the mechanisms that control the start-up of volcanic unrest is crucial to improve the forecasting of eruptions at active volcanoes. Among the most active volcanoes in the world are the so-called persistently degassing ones (e.g., Etna, Italy; Merapi, Indonesia), which emit massive amounts of gas during quiescence (several kilotonnes per day) and erupt every few months or years. The hyperactivity of these volcanoes results from frequent pressurizations of the shallow magma plumbing system, which in most cases are thought to occur by the ascent of magma from deep to shallow reservoirs. However, the driving force that causes magma ascent from depth remains unknown. Here we demonstrate that magma ascent can be triggered by the passive release of gas during quiescence, which induces the opening of pathways connecting deep and shallow magma reservoirs. This top-down mechanism for volcanic eruptions contrasts with the more common bottom-up mechanisms in which magma ascent is only driven by processes occurring at depth. A cause-effect relationship between passive degassing and magma ascent can explain the fact that repose times are typically much longer than unrest times preceding eruptions, and may account for the so frequent unrest episodes of persistently degassing volcanoes. PMID:26666396

  12. Event-triggered consensus tracking of multi-agent systems with Lur'e nonlinear dynamics

    NASA Astrophysics Data System (ADS)

    Huang, Na; Duan, Zhisheng; Wen, Guanghui; Zhao, Yu

    2016-05-01

    In this paper, distributed consensus tracking problem for networked Lur'e systems is investigated based on event-triggered information interactions. An event-triggered control algorithm is designed with the advantages of reducing controller update frequency and sensor energy consumption. By using tools of ?-procedure and Lyapunov functional method, some sufficient conditions are derived to guarantee that consensus tracking is achieved under a directed communication topology. Meanwhile, it is shown that Zeno behaviour of triggering time sequences is excluded for the proposed event-triggered rule. Finally, some numerical simulations on coupled Chua's circuits are performed to illustrate the effectiveness of the theoretical algorithms.

  13. New insights into the role of siderophores as triggers of plant immunity: what can we learn from animals?

    PubMed

    Aznar, Aude; Dellagi, Alia

    2015-06-01

    Microorganisms use siderophores to obtain iron from the environment. In pathogenic interactions, siderophores are involved in iron acquisition from the host and are sometimes necessary for the expression of full virulence. This review summarizes the main data describing the role of these iron scavengers in animal and plant defence systems. To protect themselves against iron theft, mammalian hosts have developed a hypoferremia strategy that includes siderophore-binding molecules called siderocalins. In addition to microbial ferri-siderophore sequestration, siderocalins are involved in triggering immunity. In plants, no similar mechanisms have been described and many fewer data are available, although recent advances have shed light on the role of siderophores in plant-pathogen interactions. Siderophores can trigger immunity in plants in several contexts. The most frequently described situation involving siderophores is induced systemic resistance (ISR) triggered by plant-growth-promoting rhizobacteria. Although ISR responses have been observed after treating roots with certain siderophores, the underlying mechanisms are poorly understood. Immunity can also be triggered by siderophores in leaves. Siderophore perception in plants appears to be different from the well-known perception mechanisms of other microbial compounds, known as microbe-associated molecular patterns. Scavenging iron per se appears to be a novel mechanism of immunity activation, involving complex disturbance of metal homeostasis. Receptor-specific recognition of siderophores has been described in animals, but not in plants. The review closes with an overview of the possible mechanisms of defence activation, via iron scavenging by siderophores or specific siderophore recognition by the plant host. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Cyclin-dependent kinases: engines, clocks, and microprocessors.

    PubMed

    Morgan, D O

    1997-01-01

    Cyclin-dependent kinases (Cdks) play a well-established role in the regulation of the eukaryotic cell division cycle and have also been implicated in the control of gene transcription and other processes. Cdk activity is governed by a complex network of regulatory subunits and phosphorylation events whose precise effects on Cdk conformation have been revealed by recent crystallographic studies. In the cell, these regulatory mechanisms generate an interlinked series of Cdk oscillators that trigger the events of cell division.

  15. Hypertension-misattributed kidney disease in African Americans.

    PubMed

    Skorecki, Karl L; Wasser, Walter G

    2013-01-01

    Lipkowitz et al. extend the African American Study of Kidney Disease and Hypertension to the level of genetic epidemiology, in a case-control study design. Analysis of genotypes at the APOL1 kidney disease risk region supports a paradigm shift in which genetic risk is proximate to both kidney disease and hypertension. The findings mandate urgency in clarifying mechanisms whereby APOL1 region risk variants interact with environmental triggers to cause progressive kidney disease accompanied by dangerous hypertension.

  16. Development of Energetic Actuators for Shear and Vortex Dominated Flow Control

    DTIC Science & Technology

    2014-02-19

    max-min fairness in data net- works,” Selected Areas in Communications , IEEE Journal on, vol. 9, pp. 1024 –1039, sep 1991. [ 11 ] R. G. Gallager, Poisson...the legitimate messages to route via the communication channel. Unless the secret trigger combination is known and the radio is under physical tests... 11 ]–[15], [17], [18], [29]. Covert channels are mechanisms for communicating information in ways that are difficult to detect. Packet networks are

  17. Controls on Earthquake Rupture and Triggering Mechanisms in Subduction Zones

    DTIC Science & Technology

    2010-06-01

    weaken the fault [Wibber- ley and Shimamoto, 2005]. Song and Simons [2003] infer that strongly negative TPGA values correlate with increases in the...and Y. Hu (2006), Accretionary prisms in subduction earthquake cycles: The theory of dynamic Coulomb wedge, J. Geophys. Res., 111, B06410, doi:10.1029...modified Coulomb stress function, γ is a state variable, and A is a fault constitutive parameter. We assume that the normal stress σ remains constant, and

  18. Neural assembly computing.

    PubMed

    Ranhel, João

    2012-06-01

    Spiking neurons can realize several computational operations when firing cooperatively. This is a prevalent notion, although the mechanisms are not yet understood. A way by which neural assemblies compute is proposed in this paper. It is shown how neural coalitions represent things (and world states), memorize them, and control their hierarchical relations in order to perform algorithms. It is described how neural groups perform statistic logic functions as they form assemblies. Neural coalitions can reverberate, becoming bistable loops. Such bistable neural assemblies become short- or long-term memories that represent the event that triggers them. In addition, assemblies can branch and dismantle other neural groups generating new events that trigger other coalitions. Hence, such capabilities and the interaction among assemblies allow neural networks to create and control hierarchical cascades of causal activities, giving rise to parallel algorithms. Computing and algorithms are used here as in a nonstandard computation approach. In this sense, neural assembly computing (NAC) can be seen as a new class of spiking neural network machines. NAC can explain the following points: 1) how neuron groups represent things and states; 2) how they retain binary states in memories that do not require any plasticity mechanism; and 3) how branching, disbanding, and interaction among assemblies may result in algorithms and behavioral responses. Simulations were carried out and the results are in agreement with the hypothesis presented. A MATLAB code is available as a supplementary material.

  19. Neural conflict-control mechanisms improve memory for target stimuli.

    PubMed

    Krebs, Ruth M; Boehler, Carsten N; De Belder, Maya; Egner, Tobias

    2015-03-01

    According to conflict-monitoring models, conflict serves as an internal signal for reinforcing top-down attention to task-relevant information. While evidence based on measures of ongoing task performance supports this idea, implications for long-term consequences, that is, memory, have not been tested yet. Here, we evaluated the prediction that conflict-triggered attentional enhancement of target-stimulus processing should be associated with superior subsequent memory for those stimuli. By combining functional magnetic resonance imaging (fMRI) with a novel variant of a face-word Stroop task that employed trial-unique face stimuli as targets, we were able to assess subsequent (incidental) memory for target faces as a function of whether a given face had previously been accompanied by congruent, neutral, or incongruent (conflicting) distracters. In line with our predictions, incongruent distracters not only induced behavioral conflict, but also gave rise to enhanced memory for target faces. Moreover, conflict-triggered neural activity in prefrontal and parietal regions was predictive of subsequent retrieval success, and displayed conflict-enhanced functional coupling with medial-temporal lobe regions. These data provide support for the proposal that conflict evokes enhanced top-down attention to task-relevant stimuli, thereby promoting their encoding into long-term memory. Our findings thus delineate the neural mechanisms of a novel link between cognitive control and memory. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Ecdysone triggered PGRP-LC expression controls Drosophila innate immunity.

    PubMed

    Rus, Florentina; Flatt, Thomas; Tong, Mei; Aggarwal, Kamna; Okuda, Kendi; Kleino, Anni; Yates, Elisabeth; Tatar, Marc; Silverman, Neal

    2013-05-29

    Throughout the animal kingdom, steroid hormones have been implicated in the defense against microbial infection, but how these systemic signals control immunity is unclear. Here, we show that the steroid hormone ecdysone controls the expression of the pattern recognition receptor PGRP-LC in Drosophila, thereby tightly regulating innate immune recognition and defense against bacterial infection. We identify a group of steroid-regulated transcription factors as well as two GATA transcription factors that act as repressors and activators of the immune response and are required for the proper hormonal control of PGRP-LC expression. Together, our results demonstrate that Drosophila use complex mechanisms to modulate innate immune responses, and identify a transcriptional hierarchy that integrates steroid signalling and immunity in animals.

  1. Control of Tollmien-Schlichting instabilities by finite distributed wall actuation

    NASA Astrophysics Data System (ADS)

    Losse, Nikolas R.; King, Rudibert; Zengl, Marcus; Rist, Ulrich; Noack, Bernd R.

    2011-06-01

    Tollmien-Schlichting waves are one of the key mechanisms triggering the laminar-turbulent transition in a flat-plate boundary-layer flow. By damping these waves and thus delaying transition, skin friction drag can be significantly decreased. In this simulation study, a wall segment is actuated according to a control scheme based on a POD-Galerkin model driven extended Kalman filter for state estimation and a model predictive controller to dampen TS waves by negative superposition based on this information. The setup of the simulation is chosen to resemble actuation with a driven compliant wall, such as a membrane actuator. Most importantly, a method is proposed to integrate such a localized wall actuation into a Galerkin model.

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

    PubMed

    Li, Yuan-Xin; Yang, Guang-Hong

    2018-04-01

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

  3. Aperiodic Robust Model Predictive Control for Constrained Continuous-Time Nonlinear Systems: An Event-Triggered Approach.

    PubMed

    Liu, Changxin; Gao, Jian; Li, Huiping; Xu, Demin

    2018-05-01

    The event-triggered control is a promising solution to cyber-physical systems, such as networked control systems, multiagent systems, and large-scale intelligent systems. In this paper, we propose an event-triggered model predictive control (MPC) scheme for constrained continuous-time nonlinear systems with bounded disturbances. First, a time-varying tightened state constraint is computed to achieve robust constraint satisfaction, and an event-triggered scheduling strategy is designed in the framework of dual-mode MPC. Second, the sufficient conditions for ensuring feasibility and closed-loop robust stability are developed, respectively. We show that robust stability can be ensured and communication load can be reduced with the proposed MPC algorithm. Finally, numerical simulations and comparison studies are performed to verify the theoretical results.

  4. Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores.

    PubMed

    Elosegui-Artola, Alberto; Andreu, Ion; Beedle, Amy E M; Lezamiz, Ainhoa; Uroz, Marina; Kosmalska, Anita J; Oria, Roger; Kechagia, Jenny Z; Rico-Lastres, Palma; Le Roux, Anabel-Lise; Shanahan, Catherine M; Trepat, Xavier; Navajas, Daniel; Garcia-Manyes, Sergi; Roca-Cusachs, Pere

    2017-11-30

    YAP is a mechanosensitive transcriptional activator with a critical role in cancer, regeneration, and organ size control. Here, we show that force applied to the nucleus directly drives YAP nuclear translocation by decreasing the mechanical restriction of nuclear pores to molecular transport. Exposure to a stiff environment leads cells to establish a mechanical connection between the nucleus and the cytoskeleton, allowing forces exerted through focal adhesions to reach the nucleus. Force transmission then leads to nuclear flattening, which stretches nuclear pores, reduces their mechanical resistance to molecular transport, and increases YAP nuclear import. The restriction to transport is further regulated by the mechanical stability of the transported protein, which determines both active nuclear transport of YAP and passive transport of small proteins. Our results unveil a mechanosensing mechanism mediated directly by nuclear pores, demonstrated for YAP but with potential general applicability in transcriptional regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Gas Hydrate Exploration, Mid Chilean Coast; Geochemical-Geophysical Survey

    DTIC Science & Technology

    2006-12-27

    design for the piston core provided a more safe core delivery and retrieval protocol with changes in the messenger weight and triggering mechanism ...selection of samples that were analyzed onboard depended on key data needed to assist in sample station selection and the ability to transport and...weight and triggering mechanism . Through the cruise there were 17 piston coring attempts resulting in 15 successful cores. Failures in the core

  6. Trap gun: an unusual firearm, aimed at wild animals but causing a silent epidemic of human fatalities.

    PubMed

    Kodikara, Sarathchandra; Kudagama, Muditha

    2014-03-01

    Among a variety of uncommon firearms of different origin used worldwide, the trap gun used in Sri Lanka is underreported. This is an illegal, locally made, smooth-bore, long-barreled, muzzle-loading firearm with a victim-activated simple trigger mechanism. It is mainly used to protect crops and livestock from the potential harm by wild animals. Trap gun is mounted horizontally on pegs of sticks fixed to the ground. Miscellaneous metal pieces are used as ammunition. A small metal container filled with powdered matchstick heads/firecrackers covered by the striker surface of the matchstick box is used as the percussion cap. A metal hammer is set to hit the percussion cap. Through a lever mechanism, the hammer is kept under tension. The lever mechanism is connected to a trigger cord, which runs across the animal path. The first passerby, a human being or a wild animal, who accidentally trips the trigger cord and activates the trigger mechanism is critically injured. This characteristically damages the lower limbs of the human being. This communication highlights a death due to trap gun injury. The injury pattern caused by trap gun could overlap with that of shotgun and rifled firearm. A meticulous autopsy could sort it out.

  7. Mechanical stimulation by osmotic and hydrostatic pressure activates Drosophila oocytes in vitro in a calcium-dependent manner

    PubMed Central

    Horner, Vanessa L.; Wolfner, Mariana F.

    2008-01-01

    Summary Embryogenesis in vertebrates and marine invertebrates begins when a mature oocyte is fertilized, resulting in a rise in intracellular calcium (Ca2+) that activates development. Insect eggs activate without fertilization via an unknown signal imparted to the egg during ovulation or egg laying. One hypothesis for the activating signal is that deformation of eggs as they pass through a tight orifice provides a mechanical stimulus to trigger activation. Ovulation could produce two forms of mechanical stimulus: external pressure resulting from the passage of oocytes from the ovary into the narrow oviducts, and osmotic pressure caused by hydration-induced swelling of the oocyte within the oviducts. Ovulation could also trigger activation by placing the oocyte in a new environment that contains an activating substance, such as a particular ion. Here, we provide the first evidence that Drosophila oocytes require Ca2+ for activation, and that activation can be triggered in vitro by mechanical stimuli, specifically osmotic and hydrostatic pressure. Our results suggest that activation in Drosophila is triggered by a mechanosensitive process that allows external Ca2+ to enter the oocyte and drive the events of activation. This will allow exploitation of Drosophila genetics to dissect molecular pathways involving Ca2+ and the activation of development. PMID:18304524

  8. Autonomic responses to cold face stimulation in sickle cell disease: a time-varying model analysis.

    PubMed

    Chalacheva, Patjanaporn; Kato, Roberta M; Sangkatumvong, Suvimol; Detterich, Jon; Bush, Adam; Wood, John C; Meiselman, Herbert; Coates, Thomas D; Khoo, Michael C K

    2015-07-14

    Sickle cell disease (SCD) is characterized by sudden onset of painful vaso-occlusive crises (VOC), which occur on top of the underlying chronic blood disorder. The mechanisms that trigger VOC remain elusive, but recent work suggests that autonomic dysfunction may be an important predisposing factor. Heart-rate variability has been employed in previous studies, but the derived indices have provided only limited univariate information about autonomic cardiovascular control in SCD. To circumvent this limitation, a time-varying modeling approach was applied to investigate the functional mechanisms relating blood pressure (BP) and respiration to heart rate and peripheral vascular resistance in healthy controls, untreated SCD subjects and SCD subjects undergoing chronic transfusion therapy. Measurements of respiration, heart rate, continuous noninvasive BP and peripheral vascular resistance were made before, during and after the application of cold face stimulation (CFS), which perturbs both the parasympathetic and sympathetic nervous systems. Cardiac baroreflex sensitivity estimated from the model was found to be impaired in nontransfused SCD subjects, but partially restored in SCD subjects undergoing transfusion therapy. Respiratory-cardiac coupling gain was decreased in SCD and remained unchanged by chronic transfusion. These results are consistent with autonomic dysfunction in the form of impaired parasympathetic control and sympathetic overactivity. As well, CFS led to a significant reduction in vascular resistance baroreflex sensitivity in the nontransfused SCD subjects but not in the other groups. This blunting of the baroreflex control of peripheral vascular resistance during elevated sympathetic drive could be a potential factor contributing to the triggering of VOC in SCD. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  9. REM sleep-like episodes of motoneuronal depression and respiratory rate increase are triggered by pontine carbachol microinjections in in situ perfused rat brainstem preparation

    PubMed Central

    Brandes, Ivo F.; Stettner, Georg M.; Mörschel, Michael; Kubin, Leszek; Dutschmann, Mathias

    2015-01-01

    Hypoglossal nerve activity (HNA) controls the position and movements of the tongue. In persons with compromised upper airway anatomy, sleep-related hypotonia of the tongue and other pharyngeal muscles causes increased upper airway resistance, or total upper airway obstructions, thus disrupting both sleep and breathing. Hypoglossal nerve activity reaches its nadir, and obstructive episodes are longest and most severe, during rapid eye movement stage of sleep (REMS). Microinjections of a cholinergic agonist, carbachol, into the pons have been used in vivo to investigate the mechanisms of respiratory control during REMS. Here, we recorded inspiratory-modulated phrenic nerve activity and HNA and microinjected carbachol (25–50 nl, 10 mm) into the pons in an in situ perfused working heart–brainstem rat preparation (WHBP), an ex vivo model previously validated for studies of the chemical and reflex control of breathing. Carbachol microinjections were made into 40 sites in 33 juvenile rat preparations and, at 24 sites, they triggered depression of HNA with increased respiratory rate and little change of phrenic nerve activity, a pattern akin to that during natural REMS in vivo. The REMS-like episodes started 151±73 s (SD) following microinjections, lasted 20.3±4.5 min, were elicited most effectively from the dorsal part of the rostral nucleus pontis oralis, and were prevented by perfusion of the preparation with atropine. The WHBP offers a novel model with which to investigate cellular and neurochemical mechanisms of REMS-related upper airway hypotonia in situ without anaesthesia and with full control over the cellular environment. PMID:21335420

  10. Aluminum Toxicity Is Associated with Mitochondrial Dysfunction and the Production of Reactive Oxygen Species in Plant Cells1

    PubMed Central

    Yamamoto, Yoko; Kobayashi, Yukiko; Devi, S. Rama; Rikiishi, Sanae; Matsumoto, Hideaki

    2002-01-01

    Potential mechanisms of Al toxicity measured as Al-induced inhibition of growth in cultured tobacco cells (Nicotiana tabacum, nonchlorophyllic cell line SL) and pea (Pisum sativum) roots were investigated. Compared with the control treatment without Al, the accumulation of Al in tobacco cells caused instantaneously the repression of mitochondrial activities [monitored by the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and the uptake of Rhodamine 123] and, after a lag of about 12 h, triggered reactive oxygen species (ROS) production, respiration inhibition, ATP depletion, and the loss of growth capability almost simultaneously. The presence of an antioxidant, butylated hydroxyanisol, during Al treatment of SL cells prevented not only ROS production but also ATP depletion and the loss of growth capability, suggesting that the Al-triggered ROS production seems to be a cause of ATP depletion and the loss of growth capability. Furthermore, these three late events were similarly repressed in an Al-tolerant cell line (ALT301) isolated from SL cells, suggesting that the acquisition of antioxidant functions mimicking butylated hydroxyanisol can be a mechanism of Al tolerance. In the pea root, Al also triggered ROS production, respiration inhibition, and ATP depletion, which were all correlated with inhibition of root elongation. Taken together, we conclude that Al affects mitochondrial functions, which leads to ROS production, probably the key critical event in Al inhibition of cell growth. PMID:11788753

  11. Fabrication of Protein Microparticles and Microcapsules with Biomolecular Tools

    NASA Astrophysics Data System (ADS)

    Cheung, Kwan Yee; Lai, Kwok Kei; Mak, Wing Cheung

    2018-05-01

    Microparticles have attracted much attention for medical, analytical and biological applications. Calcium carbonate (CaCO3) templating method with the advantages of having narrow size distribution, controlled morphology and good biocompatibility that has been widely used for the synthesis of various protein-based microparticles. Despite CaCO3 template is biocompatible, most of the conventional methods to create stable protein microparticles are mainly driven by chemical crosslink reagents which may induce potential harmful effect and remains undesirable especially for biomedical or clinical applications. In this article, we demonstrate the fabrication of protein microparticles and microcapsules with an innovative method using biomolecular tools such as enzymes and affinity molecules to trigger the assembling of protein molecules within a porous CaCO3 template followed by a template removal step. We demonstrated the enzyme-assisted fabrication of collagen microparticles triggered by transglutaminase, as well as the affinity-assisted fabrication of BSA-biotin avidin microcapsules triggered by biotin-avidin affinity interaction, respectively. Based on the different protein assemble mechanisms, the collagen microparticles appeared as a solid-structured particles, while the BSA-biotin avidin microcapsules appeared as hollow-structured morphology. The fabrication procedures are simple and robust that allows producing protein microparticles or microcapsules under mild conditions at physiological pH and temperature. In addition, the microparticle morphologies, protein compositions and the assemble mechanisms were studied. Our technology provides a facile approach to design and fabricate protein microparticles and microcapsules that are useful in the area of biomaterials, pharmaceuticals and analytical chemistry.

  12. Triggering the adaptive immune system with commensal gut bacteria protects against insulin resistance and dysglycemia.

    PubMed

    Pomié, Céline; Blasco-Baque, Vincent; Klopp, Pascale; Nicolas, Simon; Waget, Aurélie; Loubières, Pascale; Azalbert, Vincent; Puel, Anthony; Lopez, Frédéric; Dray, Cédric; Valet, Philippe; Lelouvier, Benjamin; Servant, Florence; Courtney, Michael; Amar, Jacques; Burcelin, Rémy; Garidou, Lucile

    2016-06-01

    To demonstrate that glycemia and insulin resistance are controlled by a mechanism involving the adaptive immune system and gut microbiota crosstalk. We triggered the immune system with microbial extracts specifically from the intestinal ileum contents of HFD-diabetic mice by the process of immunization. 35 days later, immunized mice were fed a HFD for up to two months in order to challenge the development of metabolic features. The immune responses were quantified. Eventually, adoptive transfer of immune cells from the microbiota-immunized mice to naïve mice was performed to demonstrate the causality of the microbiota-stimulated adaptive immune system on the development of metabolic disease. The gut microbiota of the immunized HFD-fed mice was characterized in order to demonstrate whether the manipulation of the microbiota to immune system interaction reverses the causal deleterious effect of gut microbiota dysbiosis on metabolic disease. Subcutaneous injection (immunization procedure) of ileum microbial extracts prevented hyperglycemia and insulin resistance in a dose-dependent manner in response to a HFD. The immunization enhanced the proliferation of CD4 and CD8 T cells in lymphoid organs, also increased cytokine production and antibody secretion. As a mechanism explaining the metabolic improvement, the immunization procedure reversed gut microbiota dysbiosis. Finally, adoptive transfer of immune cells from immunized mice improved metabolic features in response to HFD. Glycemia and insulin sensitivity can be regulated by triggering the adaptive immunity to microbiota interaction. This reduces the gut microbiota dysbiosis induced by a fat-enriched diet.

  13. GABAergic Neurons of the Central Amygdala Promote Cataplexy.

    PubMed

    Mahoney, Carrie E; Agostinelli, Lindsay J; Brooks, Jessica N K; Lowell, Bradford B; Scammell, Thomas E

    2017-04-12

    Narcolepsy is characterized by chronic sleepiness and cataplexy-sudden muscle paralysis triggered by strong, positive emotions. This condition is caused by a lack of orexin (hypocretin) signaling, but little is known about the neural mechanisms that mediate cataplexy. The amygdala regulates responses to rewarding stimuli and contains neurons active during cataplexy. In addition, lesions of the amygdala reduce cataplexy. Because GABAergic neurons of the central nucleus of the amygdala (CeA) target brainstem regions known to regulate muscle tone, we hypothesized that these cells promote emotion-triggered cataplexy. We injected adeno-associated viral vectors coding for Cre-dependent DREADDs or a control vector into the CeA of orexin knock-out mice crossed with vGAT-Cre mice, resulting in selective expression of the excitatory hM3 receptor or the inhibitory hM4 receptor in GABAergic neurons of the CeA. We measured sleep/wake behavior and cataplexy after injection of saline or the hM3/hM4 ligand clozapine -N- oxide (CNO) under baseline conditions and under conditions that should elicit positive emotions. In mice expressing hM3, CNO approximately doubled the amount of cataplexy in the first 3 h after dosing under baseline conditions. Rewarding stimuli (chocolate or running wheels) also increased cataplexy, but CNO produced no further increase. In mice expressing hM4, CNO reduced cataplexy in the presence of chocolate or running wheels. These results demonstrate that GABAergic neurons of the CeA are sufficient and necessary for the production of cataplexy in mice, and they likely are a key part of the mechanism through which positive emotions trigger cataplexy. SIGNIFICANCE STATEMENT Cataplexy is one of the major symptoms of narcolepsy, but little is known about how strong, positive emotions trigger these episodes of muscle paralysis. Prior research shows that amygdala neurons are active during cataplexy and cataplexy is reduced by lesions of the amygdala. We found that cataplexy is substantially increased by selective activation of GABAergic neurons in the central nucleus of the amygdala (CeA). We also demonstrate that inhibition of these neurons reduces reward-promoted cataplexy. These results build upon prior work to establish the CeA as a crucial element in the neural mechanisms of cataplexy. These results demonstrate the importance of the CeA in regulating responses to rewarding stimuli, shedding light on the broader neurobiology of emotions and motor control. Copyright © 2017 the authors 0270-6474/17/373995-12$15.00/0.

  14. From prediction error to incentive salience: mesolimbic computation of reward motivation.

    PubMed

    Berridge, Kent C

    2012-04-01

    Reward contains separable psychological components of learning, incentive motivation and pleasure. Most computational models have focused only on the learning component of reward, but the motivational component is equally important in reward circuitry, and even more directly controls behavior. Modeling the motivational component requires recognition of additional control factors besides learning. Here I discuss how mesocorticolimbic mechanisms generate the motivation component of incentive salience. Incentive salience takes Pavlovian learning and memory as one input and as an equally important input takes neurobiological state factors (e.g. drug states, appetite states, satiety states) that can vary independently of learning. Neurobiological state changes can produce unlearned fluctuations or even reversals in the ability of a previously learned reward cue to trigger motivation. Such fluctuations in cue-triggered motivation can dramatically depart from all previously learned values about the associated reward outcome. Thus, one consequence of the difference between incentive salience and learning can be to decouple cue-triggered motivation of the moment from previously learned values of how good the associated reward has been in the past. Another consequence can be to produce irrationally strong motivation urges that are not justified by any memories of previous reward values (and without distorting associative predictions of future reward value). Such irrationally strong motivation may be especially problematic in addiction. To understand these phenomena, future models of mesocorticolimbic reward function should address the neurobiological state factors that participate to control generation of incentive salience. © 2012 The Author. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  15. Effects of allergen and trigger factor avoidance advice in primary care on asthma control: a randomized-controlled trial.

    PubMed

    Bobb, C; Ritz, T; Rowlands, G; Griffiths, C

    2010-01-01

    Allergy contributes significantly to asthma exacerbation, yet avoidance of triggers, in particular allergens, is rarely addressed in detail in regular asthma review in primary care. To determine whether structured, individually tailored allergen and trigger avoidance advice, given as part of a primary care asthma review, improves lung function and asthma control. In a randomized-controlled trial 214 adults with asthma in six general practices were either offered usual care during a primary care asthma review or usual care with additional allergen and trigger identification (by skin prick testing and structured allergy assessment) and avoidance advice according to a standardized protocol by trained practice nurses. Main outcome measures were lung function, asthma control, asthma self-efficacy. Both intervention groups were equivalent in demographic and asthma-related variables at baseline. At 3-6-month follow-up, patients receiving the allergen and trigger avoidance review showed significant improvements in lung function (assessed by blinded research nurses) compared with those receiving usual care. Significantly more patients in the intervention group than in the control group showed improvements in forced expiratory volume in 1 s > or =15%. No significant differences were found in self-report measures of asthma control. Asthma-specific self-efficacy improved in both groups but did not differ between groups. Allergen and trigger identification and avoidance advice, given as part of a structured asthma review delivered in primary care by nurses results in clinically important improvements in lung function but not self-report of asthma control. ISRCTN45684820.

  16. The Arabidopsis immune adaptor SRFR1 interacts with TCP transcription factors that redundantly contribute to effector-triggered immunity.

    PubMed

    Kim, Sang Hee; Son, Geon Hui; Bhattacharjee, Saikat; Kim, Hye Jin; Nam, Ji Chul; Nguyen, Phuong Dung T; Hong, Jong Chan; Gassmann, Walter

    2014-06-01

    The plant immune system must be tightly controlled both positively and negatively to maintain normal plant growth and health. We previously identified SUPPRESSOR OF rps4-RLD1 (SRFR1) as a negative regulator specifically of effector-triggered immunity. SRFR1 is localized in both a cytoplasmic microsomal compartment and in the nucleus. Its TPR domain has sequence similarity to TPR domains of transcriptional repressors in other organisms, suggesting that SRFR1 may negatively regulate effector-triggered immunity via transcriptional control. We show here that excluding SRFR1 from the nucleus prevented complementation of the srfr1 phenotype. To identify transcription factors that interact with SRFR1, we screened an Arabidopsis transcription factor prey library by yeast two-hybrid assay and isolated six class I members of the TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factor family. Specific interactions were verified in planta. Although single or double T-DNA mutant tcp8, tcp14 or tcp15 lines were not more susceptible to bacteria expressing AvrRps4, the triple tcp8 tcp14 tcp15 mutant displayed decreased effector-triggered immunity mediated by the resistance genes RPS2, RPS4, RPS6 and RPM1. In addition, expression of PATHOGENESIS-RELATED PROTEIN2 was attenuated in srfr1-4 tcp8-1 tcp14-5 tcp15-3 plants compared to srfr1-4 plants. To date, TCP transcription factors have been implicated mostly in developmental processes. Our data indicate that one function of a subset of TCP proteins is to regulate defense gene expression in antagonism to SRFR1, and suggest a mechanism for an intimate connection between plant development and immunity. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  17. Factor XII full and partial null in rat confers robust antithrombotic efficacy with no bleeding.

    PubMed

    Cai, Tian-Quan; Wu, Weizhen; Shin, Myung K; Xu, Yiming; Jochnowitz, Nina; Zhou, Yuchen; Hoos, Lizbeth; Bentley, Ross; Strapps, Walter; Thankappan, Anil; Metzger, Joseph M; Ogletree, Martin L; Tadin-Strapps, Marija; Seiffert, Dietmar A; Chen, Zhu

    2015-12-01

    This report aims at exploring quantitatively the relationship between FXII inhibition and thromboprotection. FXII full and partial null in rats were established via zinc finger nuclease-mediated knockout and siRNA-mediated knockdown, respectively. The rats were subsequently characterized in thrombosis and hemostasis models. Knockout rats exhibited complete thromboprotection in both the arteriovenous shunt model (∼100% clot weight reduction) and the FeCl3-induced arterial thrombosis model (no reduction in blood flow), without any increase in cuticle bleeding time compared with wild-type control rats. Ex-vivo aPTT and the ellagic acid-triggered thrombin generation assay (TGA) exhibited anticoagulant changes. In contrast, ex-vivo PT or high tissue factor-triggered TGA was indistinguishable from control. Rats receiving single doses (0, 0.01, 0.03, 0.1, 0.3, 1 mg/kg) of FXII siRNA exhibited dose-dependent knockdown in liver FXII mRNA and plasma FXII protein (95 and 99%, respectively, at 1 mg/kg) at day 7 post dosing. FXII knockdown was associated with dose-dependent thromboprotection (maximal efficacy achieved with 1 mg/kg in both models) and negligible change in cuticle bleeding times. Ex-vivo TGA triggered with low-level (0.5 μmol/l) ellagic acid tracked best with the knockdown levels and efficacy. Our findings confirm and extend literature reports of an attractive benefit-to-risk profile of targeting FXII for antithrombotic therapies. Titrating of FXII is instructive for its pharmacological inhibition. The knockout rat is valuable for evaluating both mechanism-based safety concerns and off-target effects of FXII(a) inhibitors. Detailed TGA analyses will inform on optimal trigger conditions in studying pharmacodynamic effects of FXII(a) inhibition.

  18. Control processes through the suppression of the automatic response activation triggered by task-irrelevant information in the Simon-type tasks.

    PubMed

    Kim, Sanga; Lee, Sang Ho; Cho, Yang Seok

    2015-11-01

    The congruency sequence effect, one of the indices of cognitive control, refers to a smaller congruency effect after an incongruent than congruent trial. Although the effect has been found across a variety of conflict tasks, there is not yet agreement on the underlying mechanism. The present study investigated the mechanism underlying cognitive control by using a cross-task paradigm. In Experiments 1, 2, and 3, participants performed a modified Simon task and a spatial Stroop task alternately in a trial-by-trial manner. The task-irrelevant dimension of the two tasks was perceptually and conceptually identical in Experiment 1, whereas it was perceptually different but conceptually identical in Experiment 2. The response sets for both tasks were different in Experiment 3. In Experiment 4, participants performed two Simon tasks with different task-relevant dimensions. In all experiments in which the task-irrelevant dimension and response mode were shared, significant congruency sequence effects were found between the two different congruencies, indicating that Simon-type conflicts were resolved by a control mechanism, which is specific to an abstract task-irrelevant stimulus spatial dimension. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. How actin network dynamics control the onset of actin-based motility

    PubMed Central

    Kawska, Agnieszka; Carvalho, Kévin; Manzi, John; Boujemaa-Paterski, Rajaa; Blanchoin, Laurent; Martiel, Jean-Louis; Sykes, Cécile

    2012-01-01

    Cells use their dynamic actin network to control their mechanics and motility. These networks are made of branched actin filaments generated by the Arp2/3 complex. Here we study under which conditions the microscopic organization of branched actin networks builds up a sufficient stress to trigger sustained motility. In our experimental setup, dynamic actin networks or “gels” are grown on a hard bead in a controlled minimal protein system containing actin monomers, profilin, the Arp2/3 complex and capping protein. We vary protein concentrations and follow experimentally and through simulations the shape and mechanical properties of the actin gel growing around beads. Actin gel morphology is controlled by elementary steps including “primer” contact, growth of the network, entanglement, mechanical interaction and force production. We show that varying the biochemical orchestration of these steps can lead to the loss of network cohesion and the lack of effective force production. We propose a predictive phase diagram of actin gel fate as a function of protein concentrations. This work unveils how, in growing actin networks, a tight biochemical and physical coupling smoothens initial primer-caused heterogeneities and governs force buildup and cell motility. PMID:22908255

  20. Triggers and Anatomical Substrates in the Genesis and Perpetuation of Atrial Fibrillation

    PubMed Central

    Sánchez-Quintana, Damián; López-Mínguez, José Ramón; Pizarro, Gonzalo; Murillo, Margarita; Cabrera, José Angel

    2012-01-01

    The definition of atrial fibrillation (AF) as a functional electrical disorder does not reflect the significant underlying structural abnormalities. Atrial and Pulmonary Vein (PV) muscle sleeve microstructural remodeling is present, and establishes a vulnerable substrate for AF maintenance. In spite of an incomplete understanding of the anatomo-functional basis for AF, current evidence demonstrates that this arrhythmia usually requires a trigger for initiation and a vulnerable electrophysiological and/or anatomical substrate for maintenance. It is still unclear whether the trigger mechanisms include focal enhanced automaticity, triggered activity and/or micro re-entry from myocardial tissue. Initiation of AF can be favored by both parasympathetic and sympathetic stimulation, which also seem to play a role in maintaining AF. Finally, evolving clinical evidence demonstrates that inflammation is associated with new-onset and recurrent AF through a mechanism that possibly involves cellular degeneration, apoptosis, and subsequent atrial fibrosis. PMID:22920484

  1. Dehydration-driven stress transfer triggers intermediate-depth earthquakes

    NASA Astrophysics Data System (ADS)

    Ferrand, Thomas P.; Hilairet, Nadège; Incel, Sarah; Deldicque, Damien; Labrousse, Loïc; Gasc, Julien; Renner, Joerg; Wang, Yanbin; Green, Harry W., II; Schubnel, Alexandre

    2017-05-01

    Intermediate-depth earthquakes (30-300 km) have been extensively documented within subducting oceanic slabs, but their mechanics remains enigmatic. Here we decipher the mechanism of these earthquakes by performing deformation experiments on dehydrating serpentinized peridotites (synthetic antigorite-olivine aggregates, minerals representative of subduction zones lithologies) at upper mantle conditions. At a pressure of 1.1 gigapascals, dehydration of deforming samples containing only 5 vol% of antigorite suffices to trigger acoustic emissions, a laboratory-scale analogue of earthquakes. At 3.5 gigapascals, acoustic emissions are recorded from samples with up to 50 vol% of antigorite. Experimentally produced faults, observed post-mortem, are sealed by fluid-bearing micro-pseudotachylytes. Microstructural observations demonstrate that antigorite dehydration triggered dynamic shear failure of the olivine load-bearing network. These laboratory analogues of intermediate-depth earthquakes demonstrate that little dehydration is required to trigger embrittlement. We propose an alternative model to dehydration-embrittlement in which dehydration-driven stress transfer, rather than fluid overpressure, causes embrittlement.

  2. Emotionally triggered asthma and its relationship to panic disorder, ataques de nervios, and asthma-related death of a loved one in Latino adults.

    PubMed

    Vazquez, Karinna; Sandler, Jonathan; Interian, Alejandro; Feldman, Jonathan M

    2017-02-01

    Research has demonstrated high comorbidity between asthma and panic disorder (PD). Less is known about the relationship between asthma and the Latino cultural idiom of distress of ataques de nervios, as well as the role that psychosocial stressors play. The current study tested the hypotheses that Latino asthma patients who experience PD, ataques de nervios, and/or asthma-related death of a loved one endorse greater psychological triggers of asthma, greater perceived impact of asthma triggers, and greater difficulty controlling such triggers than do those without these conditions. Data originated from an interview conducted prior to a randomized controlled trial in which 292 Latino adults with self-reported asthma were recruited from outpatient clinics in the Bronx, NY. The PRIME-MD Patient Health Questionnaire (PHQ) was used to screen for PD symptoms, while the Structured Clinical Interview for DSM-IV (SCID-I) was used to confirm diagnosis of PD. Lifetime history of ataques de nervios and asthma-related death of a loved one were based upon self-report. Asthma triggers were examined using the Asthma Trigger Inventory (ATI). PD, ataques de nervios, and asthma-related death of a loved one each predicted a higher frequency of psychological asthma triggers, controlling for gender and comorbid medical conditions. Participants with PD also reported greater impact of asthma triggers than those without PD, while no significant differences in perceived control were observed. Providers should screen for PD, ataques de nervios, and asthma-related death of a loved one in Latino asthma patients, given their observed association with emotionally triggered asthma. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Emotionally Triggered Asthma and its Relationship to Panic Disorder, Ataques de Nervios, and Asthma-Related Death of a Loved One in Latino Adults

    PubMed Central

    Vazquez, Karinna; Sandler, Jonathan; Interian, Alejandro; Feldman, Jonathan M.

    2016-01-01

    Objective Research has demonstrated high comorbidity between asthma and panic disorder (PD). Less is known about the relationship between asthma and the Latino cultural idiom of distress of ataques de nervios, as well as the role that psychosocial stressors play. The current study tested the hypotheses that Latino asthma patients who experience PD, ataques de nervios, and/or asthma-related death of a loved one endorse greater psychological triggers of asthma, greater perceived impact of asthma triggers, and greater difficulty controlling such triggers than do those without these conditions. Methods Data originated from an interview conducted prior to a randomized controlled trial in which 292 Latino adults with self-reported asthma were recruited from outpatient clinics in the Bronx, NY. The PRIME-MD Patient Health Questionnaire (PHQ) was used to screen for PD symptoms, while the Structured Clinical Interview for DSM-IV (SCID-I) was used to confirm diagnosis of PD. Lifetime history of ataques de nervios and asthma-related death of a loved one were based upon self-report. Asthma triggers were examined using the Asthma Trigger Inventory (ATI). Results PD, ataques de nervios, and asthma-related death of a loved one each predicted a higher frequency of psychological asthma triggers, controlling for gender and comorbid medical conditions. Participants with PD also reported greater impact of asthma triggers than those without PD, while no significant differences in perceived control were observed. Conclusion Providers should screen for PD, ataques de nervios, and asthma-related death of a loved one in Latino asthma patients, given their observed association with emotionally triggered asthma. PMID:28107897

  4. Assessment of microbial contamination of radiographic equipment and materials during intraoral imaging procedures.

    PubMed

    Pinheiro, S L; Martoni, S C; Ogera, R R

    2012-05-01

    Aim of the present study was to assess microbial contamination of radiology procedures. Patients who needed radiographic exams were selected and the bisecting technique was used: G1 - (control): absence of plastic barrier and overgloving or disinfectant solutions; G2 - alcohol spraying; G3 - protection of the film with a plastic barrier and alcohol spray; G4 - protection of film with plastic barrier, use of overgloving and alcohol spray. The following regions were assessed: trigger switch, X-ray tube, sleeve of the portable dark chamber, water, developer and fixer. The areas for microbiological sample collection were standardized with a label cut internally so that the hollow area was 5 cm long and 2 cm wide. One mL of the developer, water and fixer were also collected before and after developing the films. The samples were incubated under anaerobiosis and aerobiosis. The results were submitted to the Cochran's Q and Mann-Whitney tests. The sleeve of the developing chamber showed greater anaerobic contamination followed by the X-ray tube and only the use of alcohol associated with mechanical barriers was efficient to control this microbiota. The trigger showed higher aerobic microbial contamination and the use of alcohol or alcohol associated with mechanical barriers was efficient to control this microbiota. The developing solutions presented no significant growth of anaerobic and aerobic bacteria. The characteristic of an aerobic or anaerobic microbial strain influences microbial contamination while radiographic projections are being taken and the use of alcohol associated with a plastic barrier and overgloving is indicated to reduce this microbiota.

  5. Tidal triggering of moonquakes.

    NASA Technical Reports Server (NTRS)

    Hamilton, W. L.

    1972-01-01

    It is argued that the moonquakes recorded by sensors at the Apollo 12 landing site between December 1969 and December 1970, and which according to Latham et al. (1971) are believed to be triggered by the anomalistic lunar tide, could be triggered just as well by the latitudinal (or declination) tidal wave. Considerations are set forth which indicate that a combined latitudinal-anomalistic tidal mechanism is supported by Latham's data.

  6. An E3 Ubiquitin Ligase-BAG Protein Module Controls Plant Innate Immunity and Broad-Spectrum Disease Resistance.

    PubMed

    You, Quanyuan; Zhai, Keran; Yang, Donglei; Yang, Weibing; Wu, Jingni; Liu, Junzhong; Pan, Wenbo; Wang, Jianjun; Zhu, Xudong; Jian, Yikun; Liu, Jiyun; Zhang, Yingying; Deng, Yiwen; Li, Qun; Lou, Yonggen; Xie, Qi; He, Zuhua

    2016-12-14

    Programmed cell death (PCD) and immunity in plants are tightly controlled to promote antimicrobial defense while preventing autoimmunity. However, the mechanisms contributing to this immune homeostasis are poorly understood. Here, we isolated a rice mutant ebr1 (enhanced blight and blast resistance 1) that shows enhanced broad-spectrum bacterial and fungal disease resistance, but displays spontaneous PCD, autoimmunity, and stunted growth. EBR1 encodes an E3 ubiquitin ligase that interacts with OsBAG4, which belongs to the BAG (Bcl-2-associated athanogene) family that functions in cell death, growth arrest, and immune responses in mammals. EBR1 directly targets OsBAG4 for ubiquitination-mediated degradation. Elevated levels of OsBAG4 in rice are necessary and sufficient to trigger PCD and enhanced disease resistance to pathogenic infection, most likely by activating pathogen-associated molecular patterns-triggered immunity (PTI). Together, our study suggests that an E3-BAG module orchestrates innate immune homeostasis and coordinates the trade-off between defense and growth in plants. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Apoptosis: its role in pituitary development and neoplastic pituitary tissue.

    PubMed

    Guzzo, M F; Carvalho, L R S; Bronstein, M D

    2014-04-01

    Apoptosis, also known as programmed cell death, is a phenomenon in which different stimuli trigger cellular mechanisms that culminate in death, in the absence of inflammatory cell response. Two different activation pathways are known, the intrinsic pathway (or mitochondrial) and extrinsic (or death-receptor pathway), both pathways trigger enzymatic reactions that lead cells to break up and be phagocytized by neighboring cells. This process is a common occurrence in physiological and pathological states, participating in the control of cell proliferation, differentiation and remodeling of organs. In the early steps of pituitary gland formation, numerous apoptotic cells are detected in the separation of Rathke's pouch from the roof of oral ectoderm. In the distal part of the gland, which will form the adenohypophysis, the ratio of apoptosis was significantly lower. However, there is evidence that neoplastic pituitary cells undergo unbalance in genes that control apoptosis leading to uncontrolled cell growth. No direct evidence of apoptosis was found in the drugs used for tumors producing prolactin and growth hormone. In conclusion, an unbalancing in the apoptosis process is the boundary between development and tumor growth.

  8. Effect of heating strategy on power consumption and performance of a pilot plant anaerobic digester.

    PubMed

    Espinosa-Solares, Teodoro; Valle-Guadarrama, Salvador; Bombardiere, John; Domaschko, Max; Easter, Michael

    2009-05-01

    The effect of heating strategy on power consumption and performance of a pilot plant anaerobic digester treating chicken litter, under thermophilic conditions, has been studied. Heating strategy was evaluated using three different spans (0.2 degrees C, 0.6 degrees C, and 1.0 degree C) for triggering the temperature control system from target temperature (56.7 degrees C). The hydraulic retention time in the pilot plant digester was in the range of 32 to 37 days, varying the total solids concentration fed from 5% to 6%. The results showed that under the experimental conditions, heating was the most energy-demanding process with 95.5% of the energy used. Increments up to 7.5% and 3.8%, respectively, on mechanical and heating power consumption, were observed as the span, for triggering the temperature control system from target temperature, was increased. Under the experimental conditions studied here, an increment of 30.6% on the global biodigester performance index was observed when a span of 1.0 degree C was compared to the one of 0.2 degrees C.

  9. Halloysite Nanotubes: Controlled Access and Release by Smart Gates.

    PubMed

    Cavallaro, Giuseppe; Danilushkina, Anna A; Evtugyn, Vladimir G; Lazzara, Giuseppe; Milioto, Stefana; Parisi, Filippo; Rozhina, Elvira V; Fakhrullin, Rawil F

    2017-07-28

    Hollow halloysite nanotubes have been used as nanocontainers for loading and for the triggered release of calcium hydroxide for paper preservation. A strategy for placing end-stoppers into the tubular nanocontainer is proposed and the sustained release from the cavity is reported. The incorporation of Ca(OH)₂ into the nanotube lumen, as demonstrated using transmission electron microscopy (TEM) imaging and Energy Dispersive X-ray (EDX) mapping, retards the carbonatation, delaying the reaction with CO₂ gas. This effect can be further controlled by placing the end-stoppers. The obtained material is tested for paper deacidification. We prove that adding halloysite filled with Ca(OH)₂ to paper can reduce the impact of acid exposure on both the mechanical performance and pH alteration. The end-stoppers have a double effect: they preserve the calcium hydroxide from carbonation, and they prevent from the formation of highly basic pH and trigger the response to acid exposure minimizing the pH drop-down. These features are promising for a composite nanoadditive in the smart protection of cellulose-based materials.

  10. Endocrinology of parturition

    PubMed Central

    Kota, Sunil K.; Gayatri, Kotni; Jammula, Sruti; Kota, Siva K.; Krishna, S. V. S.; Meher, Lalit K.; Modi, Kirtikumar D.

    2013-01-01

    The myometrium must remain relatively quiescent during pregnancy to accommodate growth and development of the feto-placental unit, and then must transform into a highly coordinated, strongly contracting organ at the time of labour for successful expulsion of the new born. The control of timing of labour is complex involving interactions between mother, fetus and the placenta. The timely onset of labour and delivery is an important determinant of perinatal outcome. Both preterm birth (delivery before 37 week of gestation) and post term pregnancy (pregnancy continuing beyond 42 weeks) are both associated with a significant increase in perinatal morbidity and mortality. There are multiple paracrine/autocrine events, fetal hormonal changes and overlapping maternal/fetal control mechanisms for the triggering of parturition in women. Our current article reviews the mechanisms for uterine distension and reduced contractions during pregnancy and the parturition cascade responsible for the timely and spontaneous onset of labour at term. It also discusses the mechanisms of preterm labour and post term pregnancy and the clinical implications thereof. PMID:23776853

  11. Mechanism and Regulation of DNA-Protein Crosslink Repair by the DNA-Dependent Metalloprotease SPRTN

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

    Stingele, Julian; Bellelli, Roberto; Alte, Ferdinand

    Covalent DNA-protein crosslinks (DPCs) are toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription. Little was known about DPC-specific repair mechanisms until the recent identification of a DPC-processing protease in yeast. The existence of a DPC protease in higher eukaryotes is inferred from data in Xenopus laevis egg extracts, but its identity remains elusive. Here we identify the metalloprotease SPRTN as the DPC protease acting in metazoans. Loss of SPRTN results in failure to repair DPCs and hypersensitivity to DPC-inducing agents. SPRTN accomplishes DPC processing through a unique DNA-induced protease activity, which is controlled bymore » several sophisticated regulatory mechanisms. Cellular, biochemical, and structural studies define a DNA switch triggering its protease activity, a ubiquitin switch controlling SPRTN chromatin accessibility, and regulatory autocatalytic cleavage. Our data also provide a molecular explanation on how SPRTN deficiency causes the premature aging and cancer predisposition disorder Ruijs-Aalfs syndrome.« less

  12. Mechanism and Regulation of DNA-Protein Crosslink Repair by the DNA-Dependent Metalloprotease SPRTN

    DOE PAGES

    Stingele, Julian; Bellelli, Roberto; Alte, Ferdinand; ...

    2016-10-27

    Covalent DNA-protein crosslinks (DPCs) are toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription. Little was known about DPC-specific repair mechanisms until the recent identification of a DPC-processing protease in yeast. The existence of a DPC protease in higher eukaryotes is inferred from data in Xenopus laevis egg extracts, but its identity remains elusive. Here we identify the metalloprotease SPRTN as the DPC protease acting in metazoans. Loss of SPRTN results in failure to repair DPCs and hypersensitivity to DPC-inducing agents. SPRTN accomplishes DPC processing through a unique DNA-induced protease activity, which is controlled bymore » several sophisticated regulatory mechanisms. Cellular, biochemical, and structural studies define a DNA switch triggering its protease activity, a ubiquitin switch controlling SPRTN chromatin accessibility, and regulatory autocatalytic cleavage. Our data also provide a molecular explanation on how SPRTN deficiency causes the premature aging and cancer predisposition disorder Ruijs-Aalfs syndrome.« less

  13. Silk-elastin-like protein biomaterials for the controlled delivery of therapeutics.

    PubMed

    Huang, Wenwen; Rollett, Alexandra; Kaplan, David L

    2015-05-01

    Genetically engineered biomaterials are useful for controlled delivery owing to their rational design, tunable structure-function, biocompatibility, degradability and target specificity. Silk-elastin-like proteins (SELPs), a family of genetically engineered recombinant protein polymers, possess these properties. Additionally, given the benefits of combining semi-crystalline silk-blocks and elastomeric elastin-blocks, SELPs possess multi-stimuli-responsive properties and tunability, thereby becoming promising candidates for targeted cancer therapeutics delivery and controlled gene release. An overview of SELP biomaterials for drug delivery and gene release is provided. Biosynthetic strategies used for SELP production, fundamental physicochemical properties and self-assembly mechanisms are discussed. The review focuses on sequence-structure-function relationships, stimuli-responsive features and current and potential drug delivery applications. The tunable material properties allow SELPs to be pursued as promising biomaterials for nanocarriers and injectable drug release systems. Current applications of SELPs have focused on thermally-triggered biomaterial formats for the delivery of therapeutics, based on local hyperthermia in tumors or infections. Other prominent controlled release applications of SELPs as injectable hydrogels for gene release have also been pursued. Further biomedical applications that utilize other stimuli to trigger the reversible material responses of SELPs for targeted delivery, including pH, ionic strength, redox, enzymatic stimuli and electric field, are in progress. Exploiting these additional stimuli-responsive features will provide a broader range of functional biomaterials for controlled therapeutics release and tissue regeneration.

  14. A plant effector-triggered immunity signaling sector is inhibited by pattern-triggered immunity.

    PubMed

    Hatsugai, Noriyuki; Igarashi, Daisuke; Mase, Keisuke; Lu, You; Tsuda, Yayoi; Chakravarthy, Suma; Wei, Hai-Lei; Foley, Joseph W; Collmer, Alan; Glazebrook, Jane; Katagiri, Fumiaki

    2017-09-15

    Since signaling machineries for two modes of plant-induced immunity, pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), extensively overlap, PTI and ETI signaling likely interact. In an Arabidopsis quadruple mutant, in which four major sectors of the signaling network, jasmonate, ethylene, PAD4, and salicylate, are disabled, the hypersensitive response (HR) typical of ETI is abolished when the Pseudomonas syringae effector AvrRpt2 is bacterially delivered but is intact when AvrRpt2 is directly expressed in planta These observations led us to discovery of a network-buffered signaling mechanism that mediates HR signaling and is strongly inhibited by PTI signaling. We named this mechanism the ETI-Mediating and PTI-Inhibited Sector (EMPIS). The signaling kinetics of EMPIS explain apparently different plant genetic requirements for ETI triggered by different effectors without postulating different signaling machineries. The properties of EMPIS suggest that information about efficacy of the early immune response is fed back to the immune signaling network, modulating its activity and limiting the fitness cost of unnecessary immune responses. © 2017 The Authors.

  15. Brushes, cables, and anchors: recent insights into multiscale assembly and mechanics of cellular structural networks.

    PubMed

    Lele, Tanmay P; Kumar, Sanjay

    2007-01-01

    The remarkable ability of living cells to sense, process, and respond to mechanical stimuli in their environment depends on the rapid and efficient interconversion of mechanical and chemical energy at specific times and places within the cell. For example, application of force to cells leads to conformational changes in specific mechanosensitive molecules which then trigger cellular signaling cascades that may alter cellular structure, mechanics, and migration and profoundly influence gene expression. Similarly, the sensitivity of cells to mechanical stresses is governed by the composition, architecture, and mechanics of the cellular cytoskeleton and extracellular matrix (ECM), which are in turn driven by molecular-scale forces between the constituent biopolymers. Understanding how these mechanochemical systems coordinate over multiple length and time scales to produce orchestrated cell behaviors represents a fundamental challenge in cell biology. Here, we review recent advances in our understanding of these complex processes in three experimental systems: the assembly of axonal neurofilaments, generation of tensile forces by actomyosin stress fiber bundles, and mechanical control of adhesion assembly.

  16. Photochemically Activated Motors: From Electrokinetic to Diffusion Motion Control.

    PubMed

    Zhang, Kuan; Fraxedas, Jordi; Sepulveda, Borja; Esplandiu, Maria J

    2017-12-27

    Self-propelled micro/nanomotors that can transform chemical energy from the surrounding environment into mechanical motion are cutting edge nanotechnologies with potential applications in biomedicine and environmental remediation. These applications require full understanding of the propulsion mechanisms to improve the performance and controllability of the motors. In this work, we demonstrate that there are two competing chemomechanical mechanisms at semiconductor/metal (Si/Pt) micromotors in a pump configuration under visible light exposure. The first propulsion mechanism is driven by an electro-osmotic process stemmed from a photoactivation reaction mediated by H 2 O 2 , which takes place in two separated redox reactions at the Si and Pt interfaces. One reaction involves the oxidation of H 2 O 2 at the silicon side, and the other the H 2 O 2 reduction at the metal side. The second mechanism is not light responsive and is triggered by the redox decomposition of H 2 O 2 exclusively at the Pt surface. We show that it is possible to enhance/suppress one mechanism over the other by tuning the surface roughness of the micromotor metal. More specifically, the actuation mechanism can be switched from light-controlled electrokinetics to light-insensitive diffusio-osmosis by only increasing the metal surface roughness. The different actuation mechanisms yield strikingly different fluid flow velocities, electric fields, and light sensitivities. Consequently, these findings are very relevant and can have a remarkable impact on the design and optimization of photoactivated catalytic devices and, in general, on bimetallic or insulating-metallic motors.

  17. A Contingency-Oriented Approach to Understanding Borderline Personality Disorder: Situational Triggers and Symptoms

    PubMed Central

    Miskewicz, Kelly; Fleeson, William; Arnold, Elizabeth Mayfield; Law, Mary Kate; Mneimne, Malek; Furr, R. Michael

    2015-01-01

    This article tested a contingency-oriented perspective to examine the dynamic relationships between in-the-moment borderline personality disorder (BPD) symptom events and in-the-moment triggers. An experience sampling study with 282 adults, including 77 participants with BPD, obtained reports of situational triggers and BPD symptom events five times daily for two weeks. Triggers included being rejected, betrayed, abandoned, offended, disappointed, having one’s self-concept threatened, being in a boring situation, and being alone. BPD was associated with increased situational triggers. Multilevel models revealed significant within-person associations between situational triggers and BPD symptoms for the average participant in the study, with significant individual variance in the strength and direction of trigger-symptom contingencies. Most trigger-symptom contingencies were stronger for individuals with higher borderline symptomatology, suggesting that triggers are meaningfully related to BPD. These findings highlight possible proximal mechanisms that maintain BPD and help explain the course of a disorder often described as chaotic and unpredictable. PMID:26200848

  18. Conflict-triggered top-down control: default mode, last resort, or no such thing?

    PubMed

    Bugg, Julie M

    2014-03-01

    The conflict monitoring account posits that globally high levels of conflict trigger engagement of top-down control; however, recent findings point to the mercurial nature of top-down control in high conflict contexts. The current study examined the potential moderating effect of associative learning on conflict-triggered top-down control engagement by testing the Associations as Antagonists to Top-Down Control (AATC) hypothesis. In 4 experiments, list-wide proportion congruence was manipulated, and conflict-triggered top-down control engagement was examined by comparing interference for frequency-matched, 50% congruent items across mostly congruent (low conflict) and mostly incongruent (high conflict) lists. Despite the fact that global levels of conflict were varied identically across experiments, evidence of conflict-triggered top-down control engagement was selective to those experiments in which responses could not be predicted on the majority of trials via simple associative learning, consistent with the AATC hypothesis. In a 5th experiment, older adults showed no evidence of top-down control engagement under conditions in which young adults did, a finding that refined the interpretation of the patterns observed in the prior experiments. Collectively, these findings suggest that top-down control engagement in high conflict contexts is neither the default mode nor an unused (or nonexistent) strategy. Top-down control is best characterized as a last resort that is engaged when reliance on one's environment, and in particular associative responding, is unproductive for achieving task goals.

  19. Conflict-Triggered Top-Down Control: Default Mode, Last Resort, or No Such Thing?

    PubMed Central

    Bugg, Julie M.

    2014-01-01

    The conflict monitoring account posits that globally high levels of conflict trigger engagement of top-down control; however, recent findings point to the mercurial nature of top-down control in high conflict contexts. The current study examined the potential moderating effect of associative learning on conflict-triggered top-down control engagement by testing the Associations as Antagonists to Top-Down Control (AATC) hypothesis. In 4 experiments, list-wide proportion congruence was manipulated, and conflict-triggered top-down control engagement was examined by comparing interference for 50% congruent items across mostly congruent (low conflict) and mostly incongruent (high conflict) lists. Despite the fact that global levels of conflict were varied identically across experiments, evidence of conflict-triggered top-down control engagement was selective to those experiments in which responses could not be predicted on the majority of trials via simple associative learning, consistent with the AATC hypothesis. In a fifth experiment, older adults showed no evidence of top-down control engagement under conditions in which young adults did, a finding that refined the interpretation of the patterns observed in the prior experiments. Collectively, these findings suggest that top-down control engagement in high conflict contexts is neither the default mode nor an unused (or non-existent) strategy. Top-down control is best characterized as a last resort that is engaged when reliance on one’s environment, and in particular associative responding, is unproductive for achieving task goals. PMID:24274385

  20. Suppression of friction by mechanical vibrations.

    PubMed

    Capozza, Rosario; Vanossi, Andrea; Vezzani, Alessandro; Zapperi, Stefano

    2009-08-21

    Mechanical vibrations are known to affect frictional sliding and the associated stick-slip patterns causing sometimes a drastic reduction of the friction force. This issue is relevant for applications in nanotribology and to understand earthquake triggering by small dynamic perturbations. We study the dynamics of repulsive particles confined between a horizontally driven top plate and a vertically oscillating bottom plate. Our numerical results show a suppression of the high dissipative stick-slip regime in a well-defined range of frequencies that depends on the vibrating amplitude, the normal applied load, the system inertia and the damping constant. We propose a theoretical explanation of the numerical results and derive a phase diagram indicating the region of parameter space where friction is suppressed. Our results allow to define better strategies for the mechanical control of friction.

  1. Damage Control: Cellular Mechanisms of Plasma Membrane Repair

    PubMed Central

    Andrews, Norma W.; de Almeida, Patricia E.; Corrotte, Matthias

    2014-01-01

    Summary When wounded, eukaryotic cells reseal in a few seconds. Ca2+ influx induces exocytosis of lysosomes, a process previously thought to promote repair by “patching” wounds. New evidence suggests that resealing involves direct wound removal. Exocytosis of lysosomal acid sphingomyelinase triggers endocytosis of lesions, followed by intracellular degradation. Characterization of injury-induced endosomes revealed a role for caveolae, sphingolipid-enriched plasma membrane invaginations that internalize toxin pores and are abundant in mechanically stressed cells. These findings provide a novel mechanistic explanation for the muscle pathology associated with mutations in caveolar proteins. Membrane remodeling by the ESCRT complex was also recently shown to participate in small wound repair, emphasizing that cell resealing involves previously unrecognized mechanisms for lesion removal, which are distinct from the “patch” model. PMID:25150593

  2. In vitro selection of shape-changing DNA nanostructures capable of binding-induced cargo release.

    PubMed

    Oh, Seung Soo; Plakos, Kory; Xiao, Yi; Eisenstein, Michael; Soh, H Tom

    2013-11-26

    Many biological systems employ allosteric regulatory mechanisms, which offer a powerful means of directly linking a specific binding event to a wide spectrum of molecular functionalities. There is considerable interest in generating synthetic allosteric regulators that can perform useful molecular functions for applications in diagnostics, imaging and targeted therapies, but generating such molecules through either rational design or directed evolution has proven exceptionally challenging. To address this need, we present an in vitro selection strategy for generating conformation-switching DNA nanostructures that selectively release a small-molecule payload in response to binding of a specific trigger molecule. As an exemplar, we have generated a DNA nanostructure that hybridizes with a separate 'cargo strand' containing an abasic site. This abasic site stably sequesters a fluorescent cargo molecule in an inactive state until the DNA nanostructure encounters an ATP trigger molecule. This ATP trigger causes the nanostructure to release the cargo strand, thereby liberating the fluorescent payload and generating a detectable fluorescent readout. Our DNA nanostructure is highly sensitive, with an EC50 of 30 μM, and highly specific, releasing its payload in response to ATP but not to other chemically similar nucleotide triphosphates. We believe that this selection approach could be generalized to generate synthetic nanostructures capable of selective and controlled release of other small-molecule cargos in response to a variety of triggers, for both research and clinical applications.

  3. Peptide hydrogelation triggered by enzymatic induced pH switch

    NASA Astrophysics Data System (ADS)

    Cheng, Wei; Li, Ying

    2016-07-01

    It remains challenging to develop methods that can precisely control the self-assembling kinetics and thermodynamics of peptide hydrogelators to achieve hydrogels with optimal properties. Here we report the hydrogelation of peptide hydrogelators by an enzymatically induced pH switch, which involves the combination of glucose oxidase and catalase with D-glucose as the substrate, in which both the gelation kinetics and thermodynamics can be controlled by the concentrations of D-glucose. This novel hydrogelation method could result in hydrogels with higher mechanical stability and lower hydrogelation concentrations. We further illustrate the application of this hydrogelation method to differentiate different D-glucose levels.

  4. The Brain Basis for Misophonia.

    PubMed

    Kumar, Sukhbinder; Tansley-Hancock, Olana; Sedley, William; Winston, Joel S; Callaghan, Martina F; Allen, Micah; Cope, Thomas E; Gander, Phillip E; Bamiou, Doris-Eva; Griffiths, Timothy D

    2017-02-20

    Misophonia is an affective sound-processing disorder characterized by the experience of strong negative emotions (anger and anxiety) in response to everyday sounds, such as those generated by other people eating, drinking, chewing, and breathing [1-8]. The commonplace nature of these sounds (often referred to as "trigger sounds") makes misophonia a devastating disorder for sufferers and their families, and yet nothing is known about the underlying mechanism. Using functional and structural MRI coupled with physiological measurements, we demonstrate that misophonic subjects show specific trigger-sound-related responses in brain and body. Specifically, fMRI showed that in misophonic subjects, trigger sounds elicit greatly exaggerated blood-oxygen-level-dependent (BOLD) responses in the anterior insular cortex (AIC), a core hub of the "salience network" that is critical for perception of interoceptive signals and emotion processing. Trigger sounds in misophonics were associated with abnormal functional connectivity between AIC and a network of regions responsible for the processing and regulation of emotions, including ventromedial prefrontal cortex (vmPFC), posteromedial cortex (PMC), hippocampus, and amygdala. Trigger sounds elicited heightened heart rate (HR) and galvanic skin response (GSR) in misophonic subjects, which were mediated by AIC activity. Questionnaire analysis showed that misophonic subjects perceived their bodies differently: they scored higher on interoceptive sensibility than controls, consistent with abnormal functioning of AIC. Finally, brain structural measurements implied greater myelination within vmPFC in misophonic individuals. Overall, our results show that misophonia is a disorder in which abnormal salience is attributed to particular sounds based on the abnormal activation and functional connectivity of AIC. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  5. Effect of an 8-week practice of externally triggered speech on basal ganglia activity of stuttering and fluent speakers.

    PubMed

    Toyomura, Akira; Fujii, Tetsunoshin; Kuriki, Shinya

    2015-04-01

    The neural mechanisms underlying stuttering are not well understood. It is known that stuttering appears when persons who stutter speak in a self-paced manner, but speech fluency is temporarily increased when they speak in unison with external trigger such as a metronome. This phenomenon is very similar to the behavioral improvement by external pacing in patients with Parkinson's disease. Recent imaging studies have also suggested that the basal ganglia are involved in the etiology of stuttering. In addition, previous studies have shown that the basal ganglia are involved in self-paced movement. Then, the present study focused on the basal ganglia and explored whether long-term speech-practice using external triggers can induce modification of the basal ganglia activity of stuttering speakers. Our study of functional magnetic resonance imaging revealed that stuttering speakers possessed significantly lower activity in the basal ganglia than fluent speakers before practice, especially when their speech was self-paced. After an 8-week speech practice of externally triggered speech using a metronome, the significant difference in activity between the two groups disappeared. The cerebellar vermis of stuttering speakers showed significantly decreased activity during the self-paced speech in the second compared to the first experiment. The speech fluency and naturalness of the stuttering speakers were also improved. These results suggest that stuttering is associated with defective motor control during self-paced speech, and that the basal ganglia and the cerebellum are involved in an improvement of speech fluency of stuttering by the use of external trigger. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Global Search of Triggered Tectonic Tremor

    NASA Astrophysics Data System (ADS)

    Peng, Z.; Aiken, C.; Chao, K.; Gonzalez-Huizar, H.; Wang, B.; Ojha, L.; Yang, H.

    2013-05-01

    Deep tectonic tremor has been observed at major plate-boundary faults around the Pacific Rim. While regular or ambient tremor occurs spontaneously or accompanies slow-slip events, tremor could be also triggered by large distant earthquakes and solid earth tides. Because triggered tremor occurs on the same fault patches as ambient tremor and is relatively easy to identify, a systematic global search of triggered tremor could help to identify the physical mechanisms and necessary conditions for tremor generation. Here we conduct a global search of tremor triggered by large teleseismic earthquakes. We mainly focus on major faults with significant strain accumulations where no tremor has been reported before. These includes subduction zones in Central and South America, strike-slip faults around the Caribbean plate, the Queen Charlotte-Fairweather fault system and the Denali fault in the western Canada and Alaska, the Sumatra-Java subduction zone, the Himalaya frontal thrust faults, as well as major strike-slip faults around Tibet. In each region, we first compute the predicted dynamic stresses σd from global earthquakes with magnitude>=5.0 in the past 20 years, and select events with σd > 1 kPa. Next, we download seismic data recorded by stations from local or global seismic networks, and identify triggered tremor as a high-frequency non-impulsive signal that is in phase with the large-amplitude teleseismic waves. In cases where station distributions are dense enough, we also locate tremor based on the standard envelope cross-correlation techniques. Finally, we calculate the triggering potential for the Love and Rayleigh waves with the local fault orientation and surface-wave incident angles. So far we have found several new places that are capable of generating triggered tremor. We will summarize these observations and discuss their implications on physical mechanisms of tremor and remote triggering.

  7. Materials investigation of thermal triggers used in pressure relief devices on transit buses.

    DOT National Transportation Integrated Search

    2003-07-01

    This investigation pertains to the composition and general condition of the thermally activated trigger mechanism of Pressure Relief Devices [PRD's], safety devices used on compressed natural gas cylinders commonly used to store fuel on transit buses...

  8. Thermally triggered polyrotaxane translational motion helps proton transfer.

    PubMed

    Ge, Xiaolin; He, Yubin; Liang, Xian; Wu, Liang; Zhu, Yuan; Yang, Zhengjin; Hu, Min; Xu, Tongwen

    2018-06-12

    Synthetic polyelectrolytes, capable of fast transporting protons, represent a challenging target for membrane engineering in so many fields, for example, fuel cells, redox flow batteries, etc. Inspired by the fast advance in molecular machines, here we report a rotaxane based polymer entity assembled via host-guest interaction and prove that by exploiting the thermally triggered translational motion (although not in a controlled manner) of mechanically bonded rotaxane, exceptionally fast proton transfer can be fulfilled at an external thermal input. The relative motion of the sulfonated axle to the ring in rotaxane happens at ~60 °C in our cases and because of that a proton conductivity (indicating proton transfer rate) of 260.2 mS cm -1 , which is much higher than that in the state-of-the-art Nafion, is obtained at a relatively low ion-exchange capacity (representing the amount of proton transfer groups) of 0.73 mmol g -1 .

  9. 3D pulsed laser-triggered high-speed microfluidic fluorescence-activated cell sorter

    PubMed Central

    Chen, Yue; Wu, Ting-Hsiang; Kung, Yu-Chun; Teitell, Michael A.; Chiou, Pei-Yu

    2014-01-01

    We report a 3D microfluidic pulsed laser-triggered fluorescence-activated cell sorter capable of sorting at a throughput of 23,000 cells sec−1 with 90% purity in high-purity mode and at a throughput of 45,000 cells sec−1 with 45% purity in enrichment mode in one stage and in a single channel. This performance is realized by exciting laser-induced cavitation bubbles in a 3D PDMS microfluidic channel to generate high-speed liquid jets that deflect detected fluorescent cells and particles focused by 3D sheath flows. The ultrafast switching mechanism (20 μsec complete on-off cycle), small liquid jet perturbation volume, and three-dimensional sheath flow focusing for accurate timing control of fast (1.5 m sec−1) passing cells and particles are three critical factors enabling high-purity sorting at high-throughput in this sorter. PMID:23844418

  10. A neural network for intermale aggression to establish social hierarchy.

    PubMed

    Stagkourakis, Stefanos; Spigolon, Giada; Williams, Paul; Protzmann, Jil; Fisone, Gilberto; Broberger, Christian

    2018-06-01

    Intermale aggression is used to establish social rank. Several neuronal populations have been implicated in aggression, but the circuit mechanisms that shape this innate behavior and coordinate its different components (including attack execution and reward) remain elusive. We show that dopamine transporter-expressing neurons in the hypothalamic ventral premammillary nucleus (PMv DAT neurons) organize goal-oriented aggression in male mice. Activation of PMv DAT neurons triggers attack behavior; silencing these neurons interrupts attacks. Regenerative PMv DAT membrane conductances interacting with recurrent and reciprocal excitation explain how a brief trigger can elicit a long-lasting response (hysteresis). PMv DAT projections to the ventrolateral part of the ventromedial hypothalamic and the supramammillary nuclei control attack execution and aggression reward, respectively. Brief manipulation of PMv DAT activity switched the dominance relationship between males, an effect persisting for weeks. These results identify a network structure anchored in PMv DAT neurons that organizes aggressive behavior and, as a consequence, determines intermale hierarchy.

  11. Targeted entry of enveloped viruses: measles and herpes simplex virus I.

    PubMed

    Navaratnarajah, Chanakha K; Miest, Tanner S; Carfi, Andrea; Cattaneo, Roberto

    2012-02-01

    We compare the receptor-based mechanisms that a small RNA virus and a larger DNA virus have evolved to drive the fusion of viral and cellular membranes. Both systems rely on tight control over triggering the concerted refolding of a trimeric fusion protein. While measles virus entry depends on a receptor-binding protein and a fusion protein only, the herpes simplex virus (HSV) is more complex and requires four viral proteins. Nevertheless, in both viruses a receptor-binding protein is required for triggering the membrane fusion process. Moreover, specificity domains can be appended to these receptor-binding proteins to target virus entry to cells expressing a designated receptor. We discuss how principles established with measles and HSV can be applied to targeting other enveloped viruses, and alternatively how retargeted envelopes can be fitted on foreign capsids. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Sunlight Triggers Cutaneous Lupus through a Colony Stimulating Factor-1 (CSF-1) Dependent Mechanism in MRL-Faslpr mice

    PubMed Central

    Menke, Julia; Hsu, Mei-Yu; Byrne, Katelyn T.; Lucas, Julie A.; Rabacal, Whitney A.; Croker, Byron P.; Zong, Xiao-Hua; Stanley, E. Richard; Kelley, Vicki R.

    2008-01-01

    Sunlight (UVB) triggers cutaneous (CLE) and systemic lupus through an unknown mechanism. We tested the hypothesis that UVB triggers CLE through a CSF-1-dependent, macrophage (Mø) -mediated mechanism in MRL-Faslpr mice. By constructing mutant MRL-Faslpr strains expressing varying levels of CSF-1 (high, intermediate, none), and use of an ex-vivo gene transfer to deliver CSF-1 intra-dermally, we determined that CSF-1 induces CLE in lupus-susceptible, MRL-Faslpr mice, but not in lupus-resistant, BALB/c mice. Notably, UVB incites an increase in Mø, apoptosis in the skin and CLE in MRL-Faslpr, but not in CSF-1-deficient MRL-Faslpr mice. Furthermore, UVB did not induce CLE in BALB/c mice. Probing further, UVB stimulates CSF-1 expression by keratinocytes leading to recruitment and activation of Mø that, in turn, release mediators, which induce apoptosis in keratinocytes. Thus, sunlight triggers a CSF-1-dependent, Mø-mediated destructive inflammation in the skin leading to CLE in lupus-susceptible MRL-Faslpr, but not lupus-resistant BALB/c mice. Taken together, we envision CSF-1 as the “match” and lupus-susceptibility as the “tinder” leading to CLE. PMID:18981160

  13. Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Fas(lpr) mice.

    PubMed

    Menke, Julia; Hsu, Mei-Yu; Byrne, Katelyn T; Lucas, Julie A; Rabacal, Whitney A; Croker, Byron P; Zong, Xiao-Hua; Stanley, E Richard; Kelley, Vicki R

    2008-11-15

    Sunlight (UVB) triggers cutaneous lupus erythematosus (CLE) and systemic lupus through an unknown mechanism. We tested the hypothesis that UVB triggers CLE through a CSF-1-dependent, macrophage (Mø)-mediated mechanism in MRL-Fas(lpr) mice. By constructing mutant MRL-Fas(lpr) strains expressing varying levels of CSF-1 (high, intermediate, none), and use of an ex vivo gene transfer to deliver CSF-1 intradermally, we determined that CSF-1 induces CLE in lupus-susceptible MRL-Fas(lpr) mice, but not in lupus-resistant BALB/c mice. UVB incites an increase in Møs, apoptosis in the skin, and CLE in MRL-Fas(lpr), but not in CSF-1-deficient MRL-Fas(lpr) mice. Furthermore, UVB did not induce CLE in BALB/c mice. Probing further, UVB stimulates CSF-1 expression by keratinocytes leading to recruitment and activation of Møs that, in turn, release mediators, which induce apoptosis in keratinocytes. Thus, sunlight triggers a CSF-1-dependent, Mø-mediated destructive inflammation in the skin leading to CLE in lupus-susceptible MRL-Fas(lpr) but not lupus-resistant BALB/c mice. Taken together, CSF-1 is envisioned as the match and lupus susceptibility as the tinder leading to CLE.

  14. A multi-sensor approach to landslide monitoring of rainfall-induced failures in Scotland.

    NASA Astrophysics Data System (ADS)

    Gilles, Charlie; Hoey, Trevor; Williams, Richard

    2017-04-01

    Landslides are of significant interest in upland areas of the United Kingdom due to their: complex mechanics, potential to channelize into hazardous debris flows and their costly potential impacts on infrastructure. The British Geological Survey National Landslide Database contains an average of 367 landslides per year (from 1970). Slope failures in the UK are typically triggered by extended periods of intense rainfall, and can occur at any time of year. In any given rainfall event that triggers landslides, most potentially vulnerable slopes remain stable. Accurate warning systems would be facilitated by identifying landslide precursors prior to failure events. This project tests whether such precursors can be identified in the valley of Glen Ogle, Scotland (87 km north-west of Edinburgh), where in summer 2004 two debris flows blocked the main road (A85), trapping fifty-seven people. Two adjacent sites have been selected on a west facing slope in Glen Ogle, one of which (the control) has been stable since at least 2004 and the other failed in 2004 and remains unstable. Understanding the immediate causes and antecedent conditions responsible for landslides requires a multi-scale approach. This project uses multiple sensors to assess failure mechanisms of landslides in Glen Ogle: (1) 3-monthly, high (1.8 arcsec) resolution terrestrial laser scanning of topography to detect changes and identify patterns of movement prior to major failure, using the Riegl VZ-1000 (NERC Geophysical Equipment Fund); (2) rainfall and soil moisture data to monitor pore pressure of landslide failure prior to and after hydrologically triggered events; (3) monitoring ground motion using grain-scale sensors which are becoming lower cost, more efficient in terms of power, and can be wirelessly networked these will be used to detect small scale movement of the landslide. Comparative data from the control and test sites will be presented, from which patterns of surface deformation between failure events will be derived.

  15. Migraine, arousal and sleep deprivation: comment on: "sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study".

    PubMed

    Vollono, Catello; Testani, Elisa; Losurdo, Anna; Mazza, Salvatore; Della Marca, Giacomo

    2013-06-10

    We discuss the hypothesis proposed by Engstrom and coworkers that Migraineurs have a relative sleep deprivation, which lowers the pain threshold and predispose to attacks. Previous data indicate that Migraineurs have a reduction of Cyclic Alternating Pattern (CAP), an essential mechanism of NREM sleep regulation which allows to dump the effect of incoming disruptive stimuli, and to protect sleep. The modifications of CAP observed in Migraineurs are similar to those observed in patients with impaired arousal (narcolepsy) and after sleep deprivation. The impairment of this mechanism makes Migraineurs more vulnerable to stimuli triggering attacks during sleep, and represents part of a more general vulnerability to incoming stimuli.

  16. Regulation and function of mTOR signalling in T cell fate decision

    PubMed Central

    Chi, Hongbo

    2012-01-01

    The evolutionary conserved kinase mTOR couples cell growth and metabolism to environmental inputs in eukaryotes. T cells depend on mTOR signalling to integrate immune signals and metabolic cues for their proper maintenance and activation. Under steady-state conditions, mTOR is actively controlled by multiple inhibitory mechanisms, and this enforces normal T cell homeostasis. Antigen recognition by naïve CD4+ and CD8+ T cells triggers mTOR activation, which in turn programs their differentiation into functionally distinct lineages. This Review focuses on the signalling mechanisms of mTOR in T cell homeostatic and functional fates and therapeutic implications of targeting mTOR in T cells. PMID:22517423

  17. Is Cycloxygenase-2 (COX-2) a Major Component of the Mechanism Responsible for Microvascular Remodeling in the Brain?

    NASA Astrophysics Data System (ADS)

    LaManna, Joseph C.; Sun, Xiaoyan; Ivy, Andre D.; Ward, Nicole L.

    We have used a relatively simple model of hypoxia that triggers adaptive structural changes in the cerebral microvasculature to study the process of physiological angiogenesis. This model can be used to obtain mechanistic data for the processes that probably underlie the dynamic structural changes that occur in learning and the control of oxygen availability to the neurovascular unit. These mechanisms are broadly involved in a wide variety of pathophysiological processes. This is the vascular component to CNS functional plasticity, supporting learning and adaptation. The angiogenic process may wane with age, contributing to the decreasing ability to survive metabolic stress and the diminution of neuronal plasticity.

  18. Optimal control of dissipative nonlinear dynamical systems with triggers of coupled singularities

    NASA Astrophysics Data System (ADS)

    Stevanović Hedrih, K.

    2008-02-01

    This paper analyses the controllability of motion of nonconservative nonlinear dynamical systems in which triggers of coupled singularities exist or appear. It is shown that the phase plane method is useful for the analysis of nonlinear dynamics of nonconservative systems with one degree of freedom of control strategies and also shows the way it can be used for controlling the relative motion in rheonomic systems having equivalent scleronomic conservative or nonconservative system For the system with one generalized coordinate described by nonlinear differential equation of nonlinear dynamics with trigger of coupled singularities, the functions of system potential energy and conservative force must satisfy some conditions defined by a Theorem on the existence of a trigger of coupled singularities and the separatrix in the form of "an open a spiral form" of number eight. Task of the defined dynamical nonconservative system optimal control is: by using controlling force acting to the system, transfer initial state of the nonlinear dynamics of the system into the final state of the nonlinear dynamics in the minimal time for that optimal control task

  19. The role of the supplementary motor area for speech and language processing.

    PubMed

    Hertrich, Ingo; Dietrich, Susanne; Ackermann, Hermann

    2016-09-01

    Apart from its function in speech motor control, the supplementary motor area (SMA) has largely been neglected in models of speech and language processing in the brain. The aim of this review paper is to summarize more recent work, suggesting that the SMA has various superordinate control functions during speech communication and language reception, which is particularly relevant in case of increased task demands. The SMA is subdivided into a posterior region serving predominantly motor-related functions (SMA proper) whereas the anterior part (pre-SMA) is involved in higher-order cognitive control mechanisms. In analogy to motor triggering functions of the SMA proper, the pre-SMA seems to manage procedural aspects of cognitive processing. These latter functions, among others, comprise attentional switching, ambiguity resolution, context integration, and coordination between procedural and declarative memory structures. Regarding language processing, this refers, for example, to the use of inner speech mechanisms during language encoding, but also to lexical disambiguation, syntax and prosody integration, and context-tracking. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Dynamic environmental control mechanisms for pneumatic foil constructions

    NASA Astrophysics Data System (ADS)

    Flor, Jan-Frederik; Wu, Yupeng; Beccarelli, Paolo; Chilton, John

    2017-11-01

    Membrane and foil structures have become over the last decades an attractive alternative to conventional materials and building systems with increasing implementation in different typologies and scale. The development of transparent, light, flexible and resistant materials like Ethylene Tetrafluoroethylene (ETFE) has triggered a rethinking of the building envelope in the building industry towards lightweight systems. ETFE foil cushions have proven to fulfil the design requirements in terms of structural efficiency and aesthetic values. But the strategies to satisfy increasing demands of energy efficiency and comfort conditions are still under development. The prediction and manipulation of the thermo-optical behaviour of ETFE foil cushion structures currently remain as one of the main challenges for designers and manufacturers. This paper reviews ongoing research regarding the control of the thermo-optical performance of ETFE cushion structures and highlights challenges and possible improvements. An overview of different dynamic and responsive environmental control mechanisms for multilayer foil constructions is provided and the state of the art in building application outlined by the discussion of case studies.

  1. Divergent effect of electric fields on the mechanical property of water-filled carbon nanotubes with an application as a nanoscale trigger

    NASA Astrophysics Data System (ADS)

    Ye, Hongfei; Zheng, Yonggang; Zhou, Lili; Zhao, Junfei; Zhang, Hongwu; Chen, Zhen

    2018-01-01

    Polar water molecules exhibit extraordinary phenomena under nanoscale confinement. Through the application of an electric field, a water-filled carbon nanotube (CNT) that has been successfully fabricated in the laboratory is expected to have distinct responses to the external electricity. Here, we examine the effect of electric field direction on the mechanical property of water-filled CNTs. It is observed that a longitudinal electric field enhances, but the transverse electric field reduces the elastic modulus and critical buckling stress of water-filled CNTs. The divergent effect of the electric field is attributed to the competition between the axial and circumferential pressures induced by polar water molecules. Furthermore, it is notable that the transverse electric field could result in an internal pressure with elliptical distribution, which is an effective and convenient approach to apply nonuniform pressure on nanochannels. Based on pre-strained water-filled CNTs, we designed a nanoscale trigger with an evident and rapid height change initiated by switching the direction of the electric field. The reported finding provides a foundation for an electricity-controlled property of nanochannels filled with polar molecules and provides an insight into the design of nanoscale functional devices.

  2. Altered Immune Regulation in Type 1 Diabetes

    PubMed Central

    Zóka, András; Műzes, Györgyi; Somogyi, Anikó; Varga, Tímea; Szémán, Barbara; Al-Aissa, Zahra; Hadarits, Orsolya; Firneisz, Gábor

    2013-01-01

    Research in genetics and immunology was going on separate strands for a long time. Type 1 diabetes mellitus might not be characterized with a single pathogenetic factor. It develops when a susceptible individual is exposed to potential triggers in a given sequence and timeframe that eventually disarranges the fine-tuned immune mechanisms that keep autoimmunity under control in health. Genomewide association studies have helped to understand the congenital susceptibility, and hand-in-hand with the immunological research novel paths of immune dysregulation were described in central tolerance, apoptotic pathways, or peripheral tolerance mediated by regulatory T-cells. Epigenetic factors are contributing to the immune dysregulation. The interplay between genetic susceptibility and potential triggers is likely to play a role at a very early age and gradually results in the loss of balanced autotolerance and subsequently in the development of the clinical disease. Genetic susceptibility, the impaired elimination of apoptotic β-cell remnants, altered immune regulatory functions, and environmental factors such as viral infections determine the outcome. Autoreactivity might exist under physiologic conditions and when the integrity of the complex regulatory process is damaged the disease might develop. We summarized the immune regulatory mechanisms that might have a crucial role in disease pathology and development. PMID:24285974

  3. Divergent effect of electric fields on the mechanical property of water-filled carbon nanotubes with an application as a nanoscale trigger.

    PubMed

    Ye, Hongfei; Zheng, Yonggang; Zhou, Lili; Zhao, Junfei; Zhang, Hongwu; Chen, Zhen

    2017-12-11

    Polar water molecules exhibit extraordinary phenomena under nanoscale confinement. Through the application of an electric field, a water-filled carbon nanotube (CNT) that has been successfully fabricated in the laboratory is expected to have distinct responses to the external electricity. Here, we examine the effect of electric field direction on the mechanical property of water-filled CNTs. It is observed that a longitudinal electric field enhances, but the transverse electric field reduces the elastic modulus and critical buckling stress of water-filled CNTs. The divergent effect of the electric field is attributed to the competition between the axial and circumferential pressures induced by polar water molecules. Furthermore, it is notable that the transverse electric field could result in an internal pressure with elliptical distribution, which is an effective and convenient approach to apply nonuniform pressure on nanochannels. Based on pre-strained water-filled CNTs, we designed a nanoscale trigger with an evident and rapid height change initiated by switching the direction of the electric field. The reported finding provides a foundation for an electricity-controlled property of nanochannels filled with polar molecules and provides an insight into the design of nanoscale functional devices.

  4. Bipedal gait model for precise gait recognition and optimal triggering in foot drop stimulator: a proof of concept.

    PubMed

    Shaikh, Muhammad Faraz; Salcic, Zoran; Wang, Kevin I-Kai; Hu, Aiguo Patrick

    2018-03-10

    Electrical stimulators are often prescribed to correct foot drop walking. However, commercial foot drop stimulators trigger inappropriately under certain non-gait scenarios. Past researches addressed this limitation by defining stimulation control based on automaton of a gait cycle executed by foot drop of affected limb/foot only. Since gait is a collaborative activity of both feet, this research highlights the role of normal foot for robust gait detection and stimulation triggering. A novel bipedal gait model is proposed where gait cycle is realized as an automaton based on concurrent gait sub-phases (states) from each foot. The input for state transition is fused information from feet-worn pressure and inertial sensors. Thereafter, a bipedal gait model-based stimulation control algorithm is developed. As a feasibility study, bipedal gait model and stimulation control are evaluated in real-time simulation manner on normal and simulated foot drop gait measurements from 16 able-bodied participants with three speed variations, under inappropriate triggering scenarios and with foot drop rehabilitation exercises. Also, the stimulation control employed in commercial foot drop stimulators and single foot gait-based foot drop stimulators are compared alongside. Gait detection accuracy (98.9%) and precise triggering under all investigations prove bipedal gait model reliability. This infers that gait detection leveraging bipedal periodicity is a promising strategy to rectify prevalent stimulation triggering deficiencies in commercial foot drop stimulators. Graphical abstract Bipedal information-based gait recognition and stimulation triggering.

  5. Leaf shape: genetic controls and environmental factors.

    PubMed

    Tsukaya, Hirokazu

    2005-01-01

    In recent years, many genes have been identified that are involved in the developmental processes of leaf morphogenesis. Here, I review the mechanisms of leaf shape control in a model plant, Arabidopsis thaliana, focusing on genes that fulfill special roles in leaf development. The lateral, two-dimensional expansion of leaf blades is highly dependent on the determination of the dorsoventrality of the primordia, a defining characteristic of leaves. Having a determinate fate is also a characteristic feature of leaves and is controlled by many factors. Lateral expansion is not only controlled by general regulators of cell cycling, but also by the multi-level regulation of meristematic activities, e.g., specific control of cell proliferation in the leaf-length direction, in leaf margins and in parenchymatous cells. In collaboration with the polarized control of leaf cell elongation, these redundant and specialized regulating systems for cell cycling in leaf lamina may realize the elegantly smooth, flat structure of leaves. The unified, flat shape of leaves is also dependent on the fine integration of cell proliferation and cell enlargement. Interestingly, while a decrease in the number of cells in leaf primordia can trigger a cell volume increase, an increase in the number of cells does not trigger a cell volume decrease. This phenomenon is termed compensation and suggests the existence of some systems for integration between cell cycling and cell enlargement in leaf primordia via cell-cell communication. The environmental adjustment of leaf expansion to light conditions and gravity is also summarized.

  6. The digital trigger system for the RED-100 detector

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

    Naumov, P. P., E-mail: ddr727@yandex.ru; Akimov, D. Yu.; Belov, V. A.

    The system for forming a trigger for the liquid xenon detector RED-100 is developed. The trigger can be generated for all types of events that the detector needs for calibration and data acquisition, including the events with a single electron of ionization. In the system, a mechanism of event detection is implemented according to which the timestamp and event type are assigned to each event. The trigger system is required in the systems searching for rare events to select and keep only the necessary information from the ADC array. The specifications and implementation of the trigger unit which provides amore » high efficiency of response even to low-energy events are considered.« less

  7. NaNet-10: a 10GbE network interface card for the GPU-based low-level trigger of the NA62 RICH detector.

    NASA Astrophysics Data System (ADS)

    Ammendola, R.; Biagioni, A.; Fiorini, M.; Frezza, O.; Lonardo, A.; Lamanna, G.; Lo Cicero, F.; Martinelli, M.; Neri, I.; Paolucci, P. S.; Pastorelli, E.; Piandani, R.; Pontisso, L.; Rossetti, D.; Simula, F.; Sozzi, M.; Tosoratto, L.; Vicini, P.

    2016-03-01

    A GPU-based low level (L0) trigger is currently integrated in the experimental setup of the RICH detector of the NA62 experiment to assess the feasibility of building more refined physics-related trigger primitives and thus improve the trigger discriminating power. To ensure the real-time operation of the system, a dedicated data transport mechanism has been implemented: an FPGA-based Network Interface Card (NaNet-10) receives data from detectors and forwards them with low, predictable latency to the memory of the GPU performing the trigger algorithms. Results of the ring-shaped hit patterns reconstruction will be reported and discussed.

  8. Hypothalamic Dysfunction of the Thrombospondin Receptor α2δ-1 Underlies the Overeating and Obesity Triggered by Brain-Derived Neurotrophic Factor Deficiency

    PubMed Central

    Cordeira, Joshua W.; Felsted, Jennifer A.; Teillon, Sarah; Daftary, Shabrine; Panessiti, Micaella; Wirth, Jena; Sena-Esteves, Miguel

    2014-01-01

    Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are critical components of the neural circuitry controlling appetite and body weight. Diminished BDNF signaling in mice results in severe hyperphagia and obesity. In humans, BDNF haploinsufficiency and the functional Bdnf Val66Met polymorphism have been linked to elevated food intake and body weight. The mechanisms underlying this dysfunction are poorly defined. We demonstrate a chief role of α2δ-1, a calcium channel subunit and thrombospondin receptor, in triggering overeating in mice with central BDNF depletion. We show reduced α2δ-1 cell-surface expression in the BDNF mutant ventromedial hypothalamus (VMH), an energy balance-regulating center. This deficit contributes to the hyperphagia exhibited by BDNF mutant mice because selective inhibition of α2δ-1 by gabapentin infusion into wild-type VMH significantly increases feeding and body weight gain. Importantly, viral-mediated α2δ-1 rescue in BDNF mutant VMH significantly mitigates their hyperphagia, obesity, and liver steatosis and normalizes deficits in glucose homeostasis. Whole-cell recordings in BDNF mutant VMH neurons revealed normal calcium currents but reduced frequency of EPSCs. These results suggest calcium channel-independent effects of α2δ-1 on feeding and implicate α2δ-1–thrombospondin interactions known to facilitate excitatory synapse assembly. Our findings identify a central mechanism mediating the inhibitory effects of BDNF on feeding. They also demonstrate a novel and critical role for α2δ-1 in appetite control and suggest a mechanism underlying weight gain in humans treated with gabapentinoid drugs. PMID:24403154

  9. Induction of Sirt1 by Mechanical Stretch of Skeletal Muscle through the Early Response Factor EGR1 Triggers an Antioxidative Response*

    PubMed Central

    Pardo, Patricia S.; Mohamed, Junaith S.; Lopez, Michael A.; Boriek, Aladin M.

    2011-01-01

    Mechanical loading of muscles by intrinsic muscle activity or passive stretch leads to an increase in the production of reactive oxygen species (1, 2). The NAD-dependent protein deacetylase SIRT1 is involved in the protection against oxidative stress by enhancing FOXO-driven Sod2 transcription (3–5). In this report, we unravel a mechanism triggered by mechanical stretch of skeletal muscle cells that leads to an EGR1-dependent transcriptional activation of the Sirt1 gene. The resulting transient increase in SIRT1 expression generates an antioxidative response that contributes to reactive oxygen species scavenging. PMID:20971845

  10. Optically triggered high voltage switch network and method for switching a high voltage

    DOEpatents

    El-Sharkawi, Mohamed A.; Andexler, George; Silberkleit, Lee I.

    1993-01-19

    An optically triggered solid state switch and method for switching a high voltage electrical current. A plurality of solid state switches (350) are connected in series for controlling electrical current flow between a compensation capacitor (112) and ground in a reactive power compensator (50, 50') that monitors the voltage and current flowing through each of three distribution lines (52a, 52b and 52c), which are supplying three-phase power to one or more inductive loads. An optical transmitter (100) controlled by the reactive power compensation system produces light pulses that are conveyed over optical fibers (102) to a switch driver (110') that includes a plurality of series connected optical triger circuits (288). Each of the optical trigger circuits controls a pair of the solid state switches and includes a plurality of series connected resistors (294, 326, 330, and 334) that equalize or balance the potential across the plurality of trigger circuits. The trigger circuits are connected to one of the distribution lines through a trigger capacitor (340). In each switch driver, the light signals activate a phototransistor (300) so that an electrical current flows from one of the energy reservoir capacitors through a pulse transformer (306) in the trigger circuit, producing gate signals that turn on the pair of serially connected solid state switches (350).

  11. Event-triggered output feedback control for distributed networked systems.

    PubMed

    Mahmoud, Magdi S; Sabih, Muhammad; Elshafei, Moustafa

    2016-01-01

    This paper addresses the problem of output-feedback communication and control with event-triggered framework in the context of distributed networked control systems. The design problem of the event-triggered output-feedback control is proposed as a linear matrix inequality (LMI) feasibility problem. The scheme is developed for the distributed system where only partial states are available. In this scheme, a subsystem uses local observers and share its information to its neighbors only when the subsystem's local error exceeds a specified threshold. The developed method is illustrated by using a coupled cart example from the literature. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  12. Sensitivity to Regional Earthquake Triggering and Magnitude-Frequency Characteristics of Microseismicity Detected via Matched-Filter Analysis, Central Southern Alps, New Zealand

    NASA Astrophysics Data System (ADS)

    Boese, C. M.; Townend, J.; Chamberlain, C. J.; Warren-Smith, E.

    2016-12-01

    Microseismicity recorded since 2008 by the Southern Alps Microseismicity Borehole Array (SAMBA) and other predominantly short-period seismic networks deployed in the central Southern Alps, New Zealand, reveals distinctive patterns of triggering in response to regional seismicity (magnitudes larger than 5, epicentral distances of 100-500 km). Using matched-filter detection methods implemented in the EQcorrscan package (Chamberlain et al., in prep.), we analyze microseismicity occurring in several geographically distinct swarms in order to examine the responses of specific microearthquake sources to earthquakes of different sizes occurring at different distances and azimuths. The swarms exhibit complex responses to regional seismicity which reveal that microearthquake triggering in these cases involves a combination of extrinsic factors (related to the dynamic stresses produced by the regional earthquake) and intrinsic factors (controlled by the local state of stress and possibly by hydrogeological processes). We find also that the microearthquakes detected by individual templates have Gutenberg-Richter magnitude-frequency characteristics. Since the detected events, by design, have very similar hypocentres and focal mechanisms, the observed scaling pertains to a restricted set of fault planes.

  13. Guilt and Effortful Control: Two Mechanisms that Prevent Disruptive Developmental Trajectories

    PubMed Central

    Kochanska, Grazyna; Barry, Robin A.; Jimenez, Natasha B.; Hollatz, Amanda L.; Woodard, Jarilyn

    2009-01-01

    Children's guilt associated with transgressions and their capacity for effortful control are both powerful forces that inhibit disruptive conduct. We examined how guilt and effortful control, repeatedly observed from toddler to preschool age, jointly predict children's disruptive outcomes in two multi-method multi-trait longitudinal studies (N's 57 and 99). Disruptive outcomes were rated by mothers at 73 months (Study 1) and mothers, fathers, and teachers at 52 and 67 months (Study 2). In both studies, guilt moderated effects of effortful control: For highly guilt-prone children, variations in effortful control were unrelated to future disruptive outcomes, but for children who were less guilt prone, effortful control predicted such outcomes. Guilt may inhibit transgressions through an automatic response due to negative arousal triggered by memories of past wrongdoing, regardless of child capacity for deliberate inhibition. Effortful control that engages a deliberate restraint may offset risk for disruptive conduct conferred by low guilt. PMID:19634978

  14. Molecular Regulation of Parturition: The Role of the Decidual Clock.

    PubMed

    Norwitz, Errol R; Bonney, Elizabeth A; Snegovskikh, Victoria V; Williams, Michelle A; Phillippe, Mark; Park, Joong Shin; Abrahams, Vikki M

    2015-04-27

    The timing of birth is a critical determinant of perinatal outcome. Despite intensive research, the molecular mechanisms responsible for the onset of labor both at term and preterm remain unclear. It is likely that a "parturition cascade" exists that triggers labor at term, that preterm labor results from mechanisms that either prematurely stimulate or short-circuit this cascade, and that these mechanisms involve the activation of proinflammatory pathways within the uterus. It has long been postulated that the fetoplacental unit is in control of the timing of birth through a "placental clock." We suggest that it is not a placental clock that regulates the timing of birth, but rather a "decidual clock." Here, we review the evidence in support of the endometrium/decidua as the organ primarily responsible for the timing of birth and discuss the molecular mechanisms that prime this decidual clock. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  15. Molecular Regulation of Parturition: The Role of the Decidual Clock

    PubMed Central

    Norwitz, Errol R.; Bonney, Elizabeth A.; Snegovskikh, Victoria V.; Williams, Michelle A.; Phillippe, Mark; Park, Joong Shin; Abrahams, Vikki M.

    2015-01-01

    The timing of birth is a critical determinant of perinatal outcome. Despite intensive research, the molecular mechanisms responsible for the onset of labor both at term and preterm remain unclear. It is likely that a “parturition cascade” exists that triggers labor at term, that preterm labor results from mechanisms that either prematurely stimulate or short-circuit this cascade, and that these mechanisms involve the activation of proinflammatory pathways within the uterus. It has long been postulated that the fetoplacental unit is in control of the timing of birth through a “placental clock.” We suggest that it is not a placental clock that regulates the timing of birth, but rather a “decidual clock.” Here, we review the evidence in support of the endometrium/decidua as the organ primarily responsible for the timing of birth and discuss the molecular mechanisms that prime this decidual clock. PMID:25918180

  16. Sympathetic neural control of indoleamine metabolism in the rat pineal gland

    NASA Technical Reports Server (NTRS)

    Lynch, H. J.; Hsuan, M.; Wurtman, R. J.

    1975-01-01

    The mechanisms responsible for the acceleration in rat pineal biosynthetic activity in response to prolonged exposure to darkness or to immobilization were investigated in animals whose pineals were surgically denervated. Some animals were adrenalectomized to remove one potential source of circulating catecholamines, and some were subjected to a partial chemical sympathectomy accomplished by a series of intravenous injections of 6-hydroxydopamine. Results suggest that N-acetyltransferase (NAT) activity can be enhanced either by release of norepinephrine from sympathetic terminals within the pineal or from sympathetic nerve terminals elsewhere. The stress of immobilization stimulates the pineal by increasing circulating catecholamines. Photic control of pineal function requires intact pineal sympathetic innervation, since the onset of darkness apparently does not cause a sufficient rise in circulating catecholamines to stimulate the pineal. The present studies suggest that nonspecific stress triggers increased biosynthesis and secretion of melatonin; it is possible that this hormone may participate in mechanisms of adaptation.

  17. Photothermally triggered actuation of hybrid materials as a new platform for in vitro cell manipulation

    NASA Astrophysics Data System (ADS)

    Sutton, Amy; Shirman, Tanya; Timonen, Jaakko V. I.; England, Grant T.; Kim, Philseok; Kolle, Mathias; Ferrante, Thomas; Zarzar, Lauren D.; Strong, Elizabeth; Aizenberg, Joanna

    2017-03-01

    Mechanical forces in the cell's natural environment have a crucial impact on growth, differentiation and behaviour. Few areas of biology can be understood without taking into account how both individual cells and cell networks sense and transduce physical stresses. However, the field is currently held back by the limitations of the available methods to apply physiologically relevant stress profiles on cells, particularly with sub-cellular resolution, in controlled in vitro experiments. Here we report a new type of active cell culture material that allows highly localized, directional and reversible deformation of the cell growth substrate, with control at scales ranging from the entire surface to the subcellular, and response times on the order of seconds. These capabilities are not matched by any other method, and this versatile material has the potential to bridge the performance gap between the existing single cell micro-manipulation and 2D cell sheet mechanical stimulation techniques.

  18. BK channels are required for multisensory plasticity in the oculomotor system

    PubMed Central

    Nelson, Alexandra; Faulstich, Michael; Moghadam, Setareh; Onori, Kimberly; Meredith, Andrea; du Lac, Sascha

    2017-01-01

    SUMMARY Neural circuits are endowed with several forms of intrinsic and synaptic plasticity that could contribute to adaptive changes in behavior, but circuit complexities have hindered linking specific cellular mechanisms with their behavioral consequences. Eye movements generated by simple brainstem circuits provide a means for relating cellular plasticity to behavioral gain control. Here we show that firing rate potentiation, a form of intrinsic plasticity mediated by reductions in BK-type calcium activated potassium currents in spontaneously firing neurons, is engaged during optokinetic reflex compensation for inner ear dysfunction. Vestibular loss triggers transient increases in postsynaptic excitability, occlusion of firing rate potentiation, and reductions in BK currents in vestibular nucleus neurons. Concurrently, adaptive increases in visually-evoked eye movements rapidly restore oculomotor function in wildtype mice but are profoundly impaired in BK channel null mice. Activity-dependent regulation of intrinsic excitability may be a general mechanism for adaptive control of behavioral output in multisensory circuits. PMID:27989457

  19. Membrane tension controls adhesion positioning at the leading edge of cells

    PubMed Central

    Pontes, Bruno; Gole, Laurent; Kosmalska, Anita Joanna; Tam, Zhi Yang; Luo, Weiwei; Kan, Sophie; Viasnoff, Virgile; Roca-Cusachs, Pere; Tucker-Kellogg, Lisa

    2017-01-01

    Cell migration is dependent on adhesion dynamics and actin cytoskeleton remodeling at the leading edge. These events may be physically constrained by the plasma membrane. Here, we show that the mechanical signal produced by an increase in plasma membrane tension triggers the positioning of new rows of adhesions at the leading edge. During protrusion, as membrane tension increases, velocity slows, and the lamellipodium buckles upward in a myosin II–independent manner. The buckling occurs between the front of the lamellipodium, where nascent adhesions are positioned in rows, and the base of the lamellipodium, where a vinculin-dependent clutch couples actin to previously positioned adhesions. As membrane tension decreases, protrusion resumes and buckling disappears, until the next cycle. We propose that the mechanical signal of membrane tension exerts upstream control in mechanotransduction by periodically compressing and relaxing the lamellipodium, leading to the positioning of adhesions at the leading edge of cells. PMID:28687667

  20. Rainfall-triggered shallow landslides at catchment scale: Threshold mechanics-based modeling for abruptness and localization

    NASA Astrophysics Data System (ADS)

    von Ruette, J.; Lehmann, P.; Or, D.

    2013-10-01

    Rainfall-induced shallow landslides may occur abruptly without distinct precursors and could span a wide range of soil mass released during a triggering event. We present a rainfall-induced landslide-triggering model for steep catchments with surfaces represented as an assembly of hydrologically and mechanically interconnected soil columns. The abruptness of failure was captured by defining local strength thresholds for mechanical bonds linking soil and bedrock and adjacent columns, whereby a failure of a single bond may initiate a chain reaction of subsequent failures, culminating in local mass release (a landslide). The catchment-scale hydromechanical landslide-triggering model (CHLT) was applied to results from two event-based landslide inventories triggered by two rainfall events in 2002 and 2005 in two nearby catchments located in the Prealps in Switzerland. Rainfall radar data, surface elevation and vegetation maps, and a soil production model for soil depth distribution were used for hydromechanical modeling of failure patterns for the two rainfall events at spatial and temporal resolutions of 2.5 m and 0.02 h, respectively. The CHLT model enabled systematic evaluation of the effects of soil type, mechanical reinforcement (soil cohesion and lateral root strength), and initial soil water content on landslide characteristics. We compared various landslide metrics and spatial distribution of simulated landslides in subcatchments with observed inventory data. Model parameters were optimized for the short but intense rainfall event in 2002, and the calibrated model was then applied for the 2005 rainfall, yielding reasonable predictions of landslide events and volumes and statistically reproducing localized landslide patterns similar to inventory data. The model provides a means for identifying local hot spots and offers insights into the dynamics of locally resolved landslide hazards in mountainous regions.

  1. Optical tweezers and multiphoton microscopies integrated photonic tool for mechanical and biochemical cell processes studies

    NASA Astrophysics Data System (ADS)

    de Thomaz, A. A.; Faustino, W. M.; Fontes, A.; Fernandes, H. P.; Barjas-Castro, M. d. L.; Metze, K.; Giorgio, S.; Barbosa, L. C.; Cesar, C. L.

    2007-09-01

    The research in biomedical photonics is clearly evolving in the direction of the understanding of biological processes at the cell level. The spatial resolution to accomplish this task practically requires photonics tools. However, an integration of different photonic tools and a multimodal and functional approach will be necessary to access the mechanical and biochemical cell processes. This way we can observe mechanicaly triggered biochemical events or biochemicaly triggered mechanical events, or even observe simultaneously mechanical and biochemical events triggered by other means, e.g. electricaly. One great advantage of the photonic tools is its easiness for integration. Therefore, we developed such integrated tool by incorporating single and double Optical Tweezers with Confocal Single and Multiphoton Microscopies. This system can perform 2-photon excited fluorescence and Second Harmonic Generation microscopies together with optical manipulations. It also can acquire Fluorescence and SHG spectra of specific spots. Force, elasticity and viscosity measurements of stretched membranes can be followed by real time confocal microscopies. Also opticaly trapped living protozoas, such as leishmania amazonensis. Integration with CARS microscopy is under way. We will show several examples of the use of such integrated instrument and its potential to observe mechanical and biochemical processes at cell level.

  2. Tests of remote aftershock triggering by small mainshocks using Taiwan's earthquake catalog

    NASA Astrophysics Data System (ADS)

    Peng, W.; Toda, S.

    2014-12-01

    To understand earthquake interaction and forecast time-dependent seismic hazard, it is essential to evaluate which stress transfer, static or dynamic, plays a major role to trigger aftershocks and subsequent mainshocks. Felzer and Brodsky focused on small mainshocks (2≤M<3) and their aftershocks, and then argued that only dynamic stress change brings earthquake-to-earthquake triggering, whereas Richards-Dingers et al. (2010) claimed that those selected small mainshock-aftershock pairs were not earthquake-to-earthquake triggering but simultaneous occurrence of independent aftershocks following a larger earthquake or during a significant swarm sequence. We test those hypotheses using Taiwan's earthquake catalog by taking the advantage of lacking any larger event and the absence of significant seismic swarm typically seen with active volcano. Using Felzer and Brodsky's method and their standard parameters, we only found 14 mainshock-aftershock pairs occurred within 20 km distance in Taiwan's catalog from 1994 to 2010. Although Taiwan's catalog has similar number of earthquakes as California's, the number of pairs is about 10% of the California catalog. It may indicate the effect of no large earthquakes and no significant seismic swarm in the catalog. To fully understand the properties in the Taiwan's catalog, we loosened the screening parameters to earn more pairs and then found a linear aftershock density with a power law decay of -1.12±0.38 that is very similar to the one in Felzer and Brodsky. However, none of those mainshock-aftershock pairs were associated with a M7 rupture event or M6 events. To find what mechanism controlled the aftershock density triggered by small mainshocks in Taiwan, we randomized earthquake magnitude and location. We then found that those density decay in a short time period is more like a randomized behavior than mainshock-aftershock triggering. Moreover, 5 out of 6 pairs were found in a swarm-like temporal seismicity rate increase. They locate mostly in high geothermal gradient areas, which are probably triggered by a small-scale aseismic process. Thus it rather supports the argument of Richards-Dingers et al. in which dynamic triggering by small mainshock is untenable.

  3. Central mechanisms of stress-induced headache.

    PubMed

    Cathcart, S; Petkov, J; Winefield, A H; Lushington, K; Rolan, P

    2010-03-01

    Stress is the most commonly reported trigger of an episode of chronic tension-type headache (CTTH); however, the causal significance has not been experimentally demonstrated to date. Stress may trigger CTTH through hyperalgesic effects on already sensitized pain pathways in CTTH sufferers. This hypothesis could be partially tested by examining pain sensitivity in an experimental model of stress-induced headache in CTTH sufferers. Such examinations have not been reported to date. We measured pericranial muscle tenderness and pain thresholds at the finger, head and shoulder in 23 CTTH sufferers (CTH-S) and 25 healthy control subjects (CNT) exposed to an hour-long stressful mental task, and in 23 CTTH sufferers exposed to an hour-long neutral condition (CTH-N). Headache developed in 91% of CTH-S, 4% of CNT, and 17% of CTH-N subjects. Headache sufferers had increased muscle tenderness and reduced pain thresholds compared with healthy controls. During the task, muscle tenderness increased and pain thresholds decreased in the CTH-S group compared with CTH-N and CNT groups. Pre-task muscle tenderness and reduction in pain threshold during task were predictive of the development and intensity of headache following task. The main findings are that stress induced a headache in CTTH sufferers, and this was associated with pre-task muscle tenderness and stress-induced reduction in pain thresholds. The results support the hypothesis that stress triggers CTTH through hyperalgesic effects on already increased pain sensitivity in CTTH sufferers, reducing the threshold to noxious input from pericranial structures.

  4. Effectiveness of dry needling for chronic nonspecific neck pain: a randomized, single-blinded, clinical trial.

    PubMed

    Cerezo-Téllez, Ester; Torres-Lacomba, María; Fuentes-Gallardo, Isabel; Perez-Muñoz, Milagros; Mayoral-Del-Moral, Orlando; Lluch-Girbés, Enrique; Prieto-Valiente, Luis; Falla, Deborah

    2016-09-01

    Chronic neck pain attributed to a myofascial pain syndrome is characterized by the presence of muscle contractures referred to as myofascial trigger points. In this randomized, parallel-group, blinded, controlled clinical trial, we examined the effectiveness of deep dry needling (DDN) of myofascial trigger points in people with chronic nonspecific neck pain. The study was conducted at a public Primary Health Care Centre in Madrid, Spain, from January 2010 to December 2014. A total of 130 participants with nonspecific neck pain presenting with active myofascial trigger points in their cervical muscles were included. These participants were randomly allocated to receive: DDN plus stretching (n = 65) or stretching only (control group [n = 65]). Four sessions of treatment were applied over 2 weeks with a 6-month follow-up after treatment. Pain intensity, mechanical hyperalgesia, neck active range of motion, neck muscle strength, and perceived neck disability were measured at baseline, after 2 sessions of intervention, after the intervention period, and 15, 30, 90, and 180 days after the intervention. Significant and clinically relevant differences were found in favour of dry needling in all the outcomes (all P < 0.001) at both short and long follow-ups. Deep dry needling and passive stretching is more effective than passive stretching alone in people with nonspecific neck pain. The results support the use of DDN in the management of myofascial pain syndrome in people with chronic nonspecific neck pain.

  5. Hydrologic Controls on Shallow Landslide Location, Size, and Shape

    NASA Astrophysics Data System (ADS)

    Bellugi, D.; Milledge, D.; Perron, T.; McKean, J. A.; Dietrich, W.; Rulli, M.

    2012-12-01

    Shallow landslides, typically involving just the soil mantle, are principally controlled by topography, soil and root strengths, and soil thickness, and are typically triggered by storm-induced increases in pore water pressure. The response of a landscape to landslide-triggering storms will thus depend on factors such as rainfall totals, storm intensity and duration, and antecedent moisture conditions. The two dominant mechanisms that generate high pore water pressures at a point are topographically-steered lateral subsurface flow (over timescales of days to weeks), and rapid vertical infiltration (over timescales of minutes to hours). We aim to understand the impact of different storm characteristics and hydrologic regimes on shallow landslide location, size, and shape. We have developed a regional-scale model, which applies a low-parameter grid-based multi-dimensional slope stability model within a novel search algorithm, to generate discrete landslide predictions. This model shows that the spatial organization of parameters such as root strength and pore water pressure has a strong control on shallow landslide location, size, and shape. We apply this model to a field site near Coos Bay, OR, where a ten-year landslide inventory has been mapped onto high-resolution topographic data. Our model predicts landslide size generally increases with increasing rainfall intensity, except when root strength is extremely high and pore pressures are topographically steered. The distribution of topographic index values (the ratios of contributing area to slope) of predicted landslides is a clear signature of the pore water pressure generation mechanism: as laterally dominated flow increases, landslides develop in locations with lower slopes and higher contributing areas; in contrast, in the case of vertically-dominated pore pressure rise, landslides are consistently found in locations with higher slopes and lower contributing areas. While in both cases landslides are found in the hollows, where the soils are sufficiently deep to overcome the effects of root strength, in the laterally-dominated case they are predicted to occur further down the hollows (which matches field observations). The size distribution of landslides is better predicted in our model when vertical infiltration dominates, but the observed distribution of topographic index values follows that predicted when lateral flow dominates. This suggests that both mechanisms must be taken into account in order to capture both location and size of shallow landslides (consistent with field observations). These results suggest that this modeling approach could allow us to use observed landslide locations and geometries to infer the dominant hydrologic triggering mechanisms. Furthermore, as the spatial and temporal resolution of precipitation forecasting improves, this model will enable us to more accurately predict both location and size of shallow landslides.

  6. Testing of the coalescence mechanism in high energy heavy ion collisions using two-particle correlations with identified particle trigger

    NASA Astrophysics Data System (ADS)

    Choudhury, Subikash; Sarkar, Debojit; Chattopadhyay, Subhasis

    2016-05-01

    In central Au-Au collisions at top RHIC energy, two-particle correlation measurements with identified hadron trigger have shown attenuation of near-side proton triggered jetlike yield at intermediate transverse momentum (p T ),2

  7. Neurophysiology Summary

    NASA Technical Reports Server (NTRS)

    Paloski, William H.

    2001-01-01

    The terrestrial gravitational field serves as an important orientation reference for human perception and movement, being continually monitored by sensory receptors in the skin, muscles, joints, and vestibular otolith organs. Cues from these graviceptors are used by the brain to estimate spatial orientation and to control balance and movement. Changes in these cues associated with the tonic changes in gravity (gravito-inertial force),during the launch and entry phases of space flight missions result in altered perceptions, degraded motor control performance, and in some cases, "motion" sickness during, and for a period of time after, the g-transitions. In response to these transitions, however, physiological and behavioral response mechanisms are triggered to compensate for altered graviceptor cues and/or to adapt to the new sensory environment. Basic research in the neurophysiology discipline is focused on understanding the characteristic features of and the underlying mechanisms for the normal human response to tonic changes in the gravito-inertial force environment. These studies address fundamental questions regarding the role of graviceptors in orientation and movement in the terrestrial environment, as well as the capacity, specificity, and modes for neural plasticity in the sensory-motor and perceptual systems of the brain. At the 2001 workshop basic research studies were presented addressing: neuroanatomical responses to altered gravity environments, the neural mechanisms for resolving the ambiguity between tilting and translational stimuli in otolith organ sensory input, interactions between the vestibular system and the autonomic nervous system , the roles of haptic and visual cues in spatial orientation, mechanisms for training environment-appropriate sensorimotor responses triggered by environment-specific context cues, and studies of sensori-motor control of posture and locomotion in the terrestrial environment with and without recent exposure to space flight. Building on these basic research studies are more applied studies focused on the development of countermeasures to the untoward neurophysiological responses to space flight. At the 2001 workshop, applied research studies were presented addressing issues related to the use of rotational artificial gravity (centripetal acceleration) as a multisystem (bone, muscle, cardiovascular, and, perhaps, neurovestibular) countermeasure. Also presented was a clinical study reporting on a new rating system for clinical evaluation of postflight functional neurological status.

  8. Parallel Regulation of Memory and Emotion Supports the Suppression of Intrusive Memories

    PubMed Central

    Anderson, Michael C.

    2017-01-01

    Intrusive memories often take the form of distressing images that emerge into a person's awareness, unbidden. A fundamental goal of clinical neuroscience is to understand the mechanisms allowing people to control these memory intrusions and reduce their emotional impact. Mnemonic control engages a right frontoparietal network that interrupts episodic retrieval by modulating hippocampal activity; less is known, however, about how this mechanism contributes to affect regulation. Here we report evidence in humans (males and females) that stopping episodic retrieval to suppress an unpleasant image triggers parallel inhibition of mnemonic and emotional content. Using fMRI, we found that regulation of both mnemonic and emotional content was driven by a shared frontoparietal inhibitory network and was predicted by a common profile of medial temporal lobe downregulation involving the anterior hippocampus and the amygdala. Critically, effective connectivity analysis confirmed that reduced amygdala activity was not merely an indirect consequence of hippocampal suppression; rather, both the hippocampus and the amygdala were targeted by a top-down inhibitory control signal originating from the dorsolateral prefrontal cortex. This negative coupling was greater when unwanted memories intruded into awareness and needed to be purged. Together, these findings support the broad principle that retrieval suppression is achieved by regulating hippocampal processes in tandem with domain-specific brain regions involved in reinstating specific content, in an activity-dependent fashion. SIGNIFICANCE STATEMENT Upsetting events sometimes trigger intrusive images that cause distress and that may contribute to psychiatric disorders. People often respond to intrusions by suppressing their retrieval, excluding them from awareness. Here we examined whether suppressing aversive images might also alter emotional responses to them, and the mechanisms underlying such changes. We found that the better people were at suppressing intrusions, the more it reduced their emotional responses to suppressed images. These dual effects on memory and emotion originated from a common right prefrontal cortical mechanism that downregulated the hippocampus and amygdala in parallel. Thus, suppressing intrusions affected emotional content. Importantly, participants who did not suppress intrusions well showed increased negative affect, suggesting that suppression deficits render people vulnerable to psychiatric disorders. PMID:28559378

  9. Intractable Headache - The Pain in Your Head that Just Won't Quit

    MedlinePlus

    ... into those things you can control (medications, life-style, triggers) and systematically work through the process of ... for Acute Migraine Headache ABC’s of Headache Trigger Management Abdominal Migraine Migraine Triggers Hypnic Headache Retinal Migraine ...

  10. Context-aware access control for pervasive access to process-based healthcare systems.

    PubMed

    Koufi, Vassiliki; Vassilacopoulos, George

    2008-01-01

    Healthcare is an increasingly collaborative enterprise involving a broad range of healthcare services provided by many individuals and organizations. Grid technology has been widely recognized as a means for integrating disparate computing resources in the healthcare field. Moreover, Grid portal applications can be developed on a wireless and mobile infrastructure to execute healthcare processes which, in turn, can provide remote access to Grid database services. Such an environment provides ubiquitous and pervasive access to integrated healthcare services at the point of care, thus improving healthcare quality. In such environments, the ability to provide an effective access control mechanism that meets the requirement of the least privilege principle is essential. Adherence to the least privilege principle requires continuous adjustments of user permissions in order to adapt to the current situation. This paper presents a context-aware access control mechanism for HDGPortal, a Grid portal application which provides access to workflow-based healthcare processes using wireless Personal Digital Assistants. The proposed mechanism builds upon and enhances security mechanisms provided by the Grid Security Infrastructure. It provides tight, just-in-time permissions so that authorized users get access to specific objects according to the current context. These permissions are subject to continuous adjustments triggered by the changing context. Thus, the risk of compromising information integrity during task executions is reduced.

  11. Perception of Therapeutic Qi, a Nonmechanical, Nonpsychological Factor in Acupuncture That Originates from the Therapist.

    PubMed

    Hochstrasser, Raphael J; Endler, P Christian; Klein, Sabine D

    2015-08-01

    So far, most research attempts to explain the mechanism of the action of acupuncture have focused mostly on mechanically-triggered active factors and have produced inconclusive findings. In this study, we investigate whether acupuncture might also involve nonmechanical, nonpsychological active factors originating in the therapist. In 30 individuals, an acupuncture needle was inserted in the acupoint PC6 using a special device without touching the needle. A second device was used to fix the needle rigidly in place, excluding any mechanical transmission of movement from the handle to the needle's tip. Each participant was exposed in random order to a control and a stimulation phase. During the stimulation phase, the free needle's end was held by the therapist to allow the transmission of Qi; during the control phase, it was left untouched. Participants' subjective sensations during the stimulation phase and the control phase were recorded using a questionnaire. Twenty-two of 28 (79%; p = 0.003) test participants believed that they had received stimulation when it had actually been performed, and 26 (93%; p < 0.001) sensed differences between the two experimental phases. Thus, participants were able to sense the transmission of therapeutic Qi in the absence of mechanical or psychological factors. Copyright © 2015. Published by Elsevier B.V.

  12. The neural oscillations of conflict adaptation in the human frontal region.

    PubMed

    Tang, Dandan; Hu, Li; Chen, Antao

    2013-07-01

    Incongruency between print color and the semantic meaning of a word in a classical Stroop task activates the human conflict monitoring system and triggers a behavioral conflict. Conflict adaptation has been suggested to mediate the cortical processing of neural oscillations in such a conflict situation. However, the basic mechanisms that underlie the influence of conflict adaptation on the changes of neural oscillations are not clear. In the present study, electroencephalography (EEG) data were recorded from sixteen healthy human participants while they were performing a color-word Stroop task within a novel look-to-do transition design that included two response modalities. In the 'look' condition, participants were informed to look at the color of presented words but no responses were required; in the 'do' condition, they were informed to make arranged responses to the color of presented words. Behaviorally, a reliable conflict adaptation was observed. Time-frequency analysis revealed that (1) in the 'look' condition, theta-band activity in the left- and right-frontal regions reflected a conflict-related process at a response inhibition level; and (2) in the 'do' condition, both theta-band activity in the left-frontal region and alpha-band activity in the left-, right-, and centro-frontal regions reflected a process of conflict control, which triggered neural and behavioral adaptation. Taken together, these results suggest that there are frontal mechanisms involving neural oscillations that can mediate response inhibition processes and control behavioral conflict. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. High-Resolution Numerical Analysis of the Triggering Mechanism of M L5.7 Aswan Reservoir Earthquake Through Fully Coupled Poroelastic Finite Element Modeling

    NASA Astrophysics Data System (ADS)

    Cheng, Huihong; Zhang, Huai; Shi, Yaolin

    2016-05-01

    In 1981, a powerful M L5.7 earthquake occurred 50 km away from the Aswan Reservoir dam. After the statistical analysis on the correlationship between long-term continuous seismicity occurrence and the reservoir water level variation attributed to the impoundment and drainage procedures, researchers believe that this event is a typical reservoir-triggered seismicity (Nature 301(6):14, 1983; Earthquake Activity in the Aswan Region, Egypt. Birkhäuser, Basel, pp. 69-86, 1995), although its triggering mechanism is poorly understood to date. To quantitatively address the triggering mechanism as well as its relationship with the characteristics of local geological settings around the reservoir region, in this paper, a fully coupled three-dimensional poroelastic finite element model of the Aswan reservoir is put forward by taking the consideration of the realistic observation data, for example, the high-resolution topography, water level fluctuation history, flood zone boundary and water depth variation, fault parameters, etc. Meanwhile, the change of Coulomb Failure Stress (ΔCFS) in correspondence to elastic stress and pore pressure variations induced by fluid diffusion is calculated. And the elastic strain energy accumulation in the reservoir region due to the impoundment load is obtained as well. Our primary results indicate that both the pore pressure and the coulomb stress on the seismogenic fault plane gradually increase with the respect of time while the water level rises. The magnitude of ΔCFS at the hypocenter of this major event is around 0.1 MPa, suggesting that the impoundment of the Aswan Reservoir possibly triggered the M L5.7 earthquake. The contribution of the elastic load is less than 3 percent of the total ΔCFS; on the other hand, the dynamic pore pressure change predominantly accounts for the contribution. The accumulative maximum surface deformation beneath the Aswan reservoir is up to 80 cm since its impounding began until the M L5.7 earthquake occurred. Although the total elastic strain energy accumulation caused by the impoundment water load is around 1.0 × 1010J, this energy density still insignificant compared to that of the vast reservoir inundation area, as it is only less than few percent of the total energy released by the major event, which confirms that the sustained regional geological loading controls the occurrence of this large reservoir-induced event. Furthermore, elastic loading and pore fluid pore pressure diffusion due to the impoundment of the Aswan reservoir might accelerate its occurrence.

  14. Multimodality of Ca2+ signaling in rat atrial myocytes.

    PubMed

    Morad, Martin; Javaheri, Ashkan; Risius, Tim; Belmonte, Steve

    2005-06-01

    It has been suggested that the multiplicity of Ca(2+) signaling pathways in atrial myocytes may contribute to the variability of its function. This article reports on a novel Ca(2+) signaling cascade initiated by mechanical forces induced by "puffing" of solution onto the myocytes. Ca(i) transients were measured in fura-2 acetoxymethyl (AM) loaded cells using alternating 340- and 410-nm excitation waves at 1.2 kHz. Pressurized puffs of bathing solutions, applied by an electronically controlled micro-barrel system, activated slowly (approximately 300 ms) developing Ca(i) transients that lasted 1,693 +/- 68 ms at room temperature. Subsequent second and third puffs, applied at approximately 20 s intervals activated significantly smaller or no Ca(i) transients. Puff-triggered Ca(i) transients could be reactivated once again following caffeine (10 mM)-induced release of Ca(2+) from sarcoplasmic reticulum (SR). Puff-triggered Ca(i) transients were independent of [Ca(2+)](o), and activation of voltage-gated Ca(2+) or cationic stretch channels or influx of Ca(2+) on Na(+)/Ca(2+)exchanger, because puffing solution containing no Ca(2+), 10 microM diltiazem, 1 mM Cd(2+), 5 mM Ni(2+), or 100 microM Gd(3+) failed to suppress them. Puff-triggered Ca(i) transients were enhanced in paced compared to quiescent myocytes. Electrically activated Ca(i) transients triggered during the time course of puff-induced transients were unaltered, suggesting functionally separate Ca(2+) pools. Contribution of inositol 1,4,5-triphosphate (IP(3))-gated or mitochondrial Ca(2+) pools or modulation of SR stores by nitric oxide/nitric oxide synthase (NO/NOS) signaling were evaluated using 0.5 to 500 microM 2-aminoethoxydiphenyl borate (2-APB) and 0.1 to 1 microM carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), and 1 mM Nomega-Nitro-L-arginine methyl ester (L-NAME) and 7-nitroindizole, respectively. Only FCCP appeared to significantly suppress the puff-triggered Ca(i) transients. It was concluded that neither Ca(2+) influx nor depolarization was required for activation of this signaling pathway. These studies suggest that pressurized puffs of solutions activate a mechanically sensitive receptor, which signals in turn the release of Ca(2+) from a limited Ca(2+) store of mitochondria. How mechanical forces are sensed and transmitted to mitochondria to induce Ca(2+) release and what role such a Ca(2+) signaling pathway plays in the physiology or pathophysiology of the heart remain to be worked out.

  15. Studies of the Plasma Triggering Mechanism of Inverse Pinch Switch

    DTIC Science & Technology

    1993-11-10

    plasma - focus driven plasma-puff was also discussed in comparison with the hypocycloidal pinch plasma-puff triggering. The main discharge of inverse pinch switch with plasma - focus driven plasma-puff trigger is found to be more azimuthally uniform than that with hypocycloidal pinch plasma-puff trigger in a gas pressure region between 80 mTorr and 1 Torr. A comparative study of the INPIStron and a spark gap also reveals that the INPIStron with a low impedance Z = 9 ohms can transfer a high voltage pulse with a superior pulse-shape fidelity over that with

  16. Presynaptic gain control by endogenous cotransmission of dopamine and GABA in the olfactory bulb.

    PubMed

    Vaaga, Christopher E; Yorgason, Jordan T; Williams, John T; Westbrook, Gary L

    2017-03-01

    In the olfactory bulb, lateral inhibition mediated by local juxtaglomerular interneurons has been proposed as a gain control mechanism, important for decorrelating odorant responses. Among juxtaglomerular interneurons, short axon cells are unique as dual-transmitter neurons that release dopamine and GABA. To examine their intraglomerular function, we expressed channelrhodopsin under control of the DAT-cre promoter and activated olfactory afferents within individual glomeruli. Optical stimulation of labeled cells triggered endogenous dopamine release as measured by cyclic voltammetry and GABA release as measured by whole cell GABA A receptor currents. Activation of short axon cells reduced the afferent presynaptic release probability via D 2 and GABA B receptor activation, resulting in reduced spiking in both mitral and external tufted cells. Our results suggest that short axon cells influence glomerular activity not only by direct inhibition of external tufted cells but also by inhibition of afferent inputs to external tufted and mitral cells. NEW & NOTEWORTHY Sensory systems, including the olfactory system, encode information across a large dynamic range, making synaptic mechanisms of gain control critical to proper function. Here we demonstrate that a dual-transmitter interneuron in the olfactory bulb controls the gain of intraglomerular afferent input via two distinct mechanisms, presynaptic inhibition as well as inhibition of a principal neuron subtype, and thereby potently controls the synaptic gain of afferent inputs. Copyright © 2017 the American Physiological Society.

  17. Tuning acoustic and mechanical properties of materials for ultrasound phantoms and smart substrates for cell cultures.

    PubMed

    Cafarelli, A; Verbeni, A; Poliziani, A; Dario, P; Menciassi, A; Ricotti, L

    2017-02-01

    Materials with tailored acoustic properties are of great interest for both the development of tissue-mimicking phantoms for ultrasound tests and smart scaffolds for ultrasound mediated tissue engineering and regenerative medicine. In this study, we assessed the acoustic properties (speed of sound, acoustic impedance and attenuation coefficient) of three different materials (agarose, polyacrylamide and polydimethylsiloxane) at different concentrations or cross-linking levels and doped with different concentrations of barium titanate ceramic nanoparticles. The selected materials, besides different mechanical features (stiffness from few kPa to 1.6MPa), showed a wide range of acoustic properties (speed of sound from 1022 to 1555m/s, acoustic impedance from 1.02 to 1.67MRayl and attenuation coefficient from 0.2 to 36.5dB/cm), corresponding to ranges in which natural soft tissues can fall. We demonstrated that this knowledge can be used to build tissue-mimicking phantoms for ultrasound-based medical procedures and that the mentioned measurements enable to stimulate cells with a highly controlled ultrasound dose, taking into account the attenuation due to the cell-supporting scaffold. Finally, we were able to correlate for the first time the bioeffect on human fibroblasts, triggered by piezoelectric barium titanate nanoparticles activated by low-intensity pulsed ultrasound, with a precise ultrasound dose delivered. These results may open new avenues for the development of both tissue-mimicking materials for ultrasound phantoms and smart triggerable scaffolds for tissue engineering and regenerative medicine. This study reports for the first time the results of a systematic acoustic characterization of agarose, polyacrylamide and polydimethylsiloxane at different concentrations and cross-linking extents and doped with different concentrations of barium titanate nanoparticles. These results can be used to build tissue-mimicking phantoms, useful for many ultrasound-based medical procedures, and to fabricate smart materials for stimulating cells with a highly controlled ultrasound dose. Thanks to this knowledge, we correlated for the first time a bioeffect (the proliferation increase) on human fibroblasts, triggered by piezoelectric nanoparticles, with a precise US dose delivered. These results may open new avenues for the development of both tissue-mimicking phantoms and smart triggerable scaffolds for tissue engineering and regenerative medicine. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  18. Coordination of size-control, reproduction and generational memory in freshwater planarians

    NASA Astrophysics Data System (ADS)

    Yang, Xingbo; Kaj, Kelson; Schwab, David; Collins, Eva-Maria

    Uncovering the mechanisms that control size, growth, and division rates of systems reproducing through binary division means understanding basic principles of their life cycle. Recent work has focused on how division rates are regulated in bacteria and yeast, but this question has not yet been addressed in more complex, multicellular organisms. We have acquired a unique large-scale data set on the growth and asexual reproduction of two freshwater planarian species, Dugesia japonica and Dugesia tigrina, which reproduce by transverse fission and succeeding regeneration of head and tail pieces into new worms. We developed a new additive theoretical model that mixes multiple size control strategies based on worm size, growth, and waiting time. Our model quantifies the proportions of each strategy in the mixed dynamics, revealing the ability of the two planarian species to utilize different strategies in a coordinated manner for size control. Additionally, we found that head and tail offspring of both species employ different mechanisms to monitor and trigger their reproduction cycles. Finally, we show that generation-dependent memory effects in planarians need to be taken into account to accurately capture the experimental data.

  19. Defining when to initiate massive transfusion: a validation study of individual massive transfusion triggers in PROMMTT patients.

    PubMed

    Callcut, Rachael A; Cotton, Bryan A; Muskat, Peter; Fox, Erin E; Wade, Charles E; Holcomb, John B; Schreiber, Martin A; Rahbar, Mohammad H; Cohen, Mitchell J; Knudson, M Margaret; Brasel, Karen J; Bulger, Eileen M; Del Junco, Deborah J; Myers, John G; Alarcon, Louis H; Robinson, Bryce R H

    2013-01-01

    Early predictors of massive transfusion (MT) would prevent undertriage of patients likely to require MT. This study validates triggers using the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. All enrolled patients in PROMMTT were analyzed. The initial emergency department value for each trigger (international normalized ratio [INR], systolic blood pressure, hemoglobin, base deficit, positive result for Focused Assessment for the Sonography of Trauma examination, heart rate, temperature, and penetrating injury mechanism) was compared for patients receiving MT (≥ 10 U of packed red blood cells in 24 hours) versus no MT. Adjusted odds ratios (ORs) for MT are reported using multiple logistic regression. If all triggers were known, a Massive Transfusion Score (MTS) was created, with 1 point assigned for each met trigger. A total of 1,245 patients were prospectively enrolled with 297 receiving an MT. Data were available for all triggers in 66% of the patients including 67% of the MTs (199 of 297). INR was known in 87% (1,081 of 1,245). All triggers except penetrating injury mechanism and heart rate were valid individual predictors of MT, with INR as the most predictive (adjusted OR, 2.5; 95% confidence interval, 1.7-3.7). For those with all triggers known, a positive INR trigger was seen in 49% receiving MT. Patients with an MTS of less than 2 were unlikely to receive MT (negative predictive value, 89%). If any two triggers were present (MTS ≥ 2), sensitivity for predicting MT was 85%. MT was present in 33% with an MTS of 2 greater compared with 11% of those with MTS of less than 2 (OR, 3.9; 95% confidence interval, 2.6-5.8; p < 0.0005). Parameters that can be obtained early in the initial emergency department evaluation are valid predictors for determining the likelihood of MT. Diagnostic, level II.

  20. Status of the photomultiplier-based FlashCam camera for the Cherenkov Telescope Array

    NASA Astrophysics Data System (ADS)

    Pühlhofer, G.; Bauer, C.; Eisenkolb, F.; Florin, D.; Föhr, C.; Gadola, A.; Garrecht, F.; Hermann, G.; Jung, I.; Kalekin, O.; Kalkuhl, C.; Kasperek, J.; Kihm, T.; Koziol, J.; Lahmann, R.; Manalaysay, A.; Marszalek, A.; Rajda, P. J.; Reimer, O.; Romaszkan, W.; Rupinski, M.; Schanz, T.; Schwab, T.; Steiner, S.; Straumann, U.; Tenzer, C.; Vollhardt, A.; Weitzel, Q.; Winiarski, K.; Zietara, K.

    2014-07-01

    The FlashCam project is preparing a camera prototype around a fully digital FADC-based readout system, for the medium sized telescopes (MST) of the Cherenkov Telescope Array (CTA). The FlashCam design is the first fully digital readout system for Cherenkov cameras, based on commercial FADCs and FPGAs as key components for digitization and triggering, and a high performance camera server as back end. It provides the option to easily implement different types of trigger algorithms as well as digitization and readout scenarios using identical hardware, by simply changing the firmware on the FPGAs. The readout of the front end modules into the camera server is Ethernet-based using standard Ethernet switches and a custom, raw Ethernet protocol. In the current implementation of the system, data transfer and back end processing rates of 3.8 GB/s and 2.4 GB/s have been achieved, respectively. Together with the dead-time-free front end event buffering on the FPGAs, this permits the cameras to operate at trigger rates of up to several ten kHz. In the horizontal architecture of FlashCam, the photon detector plane (PDP), consisting of photon detectors, preamplifiers, high voltage-, control-, and monitoring systems, is a self-contained unit, mechanically detached from the front end modules. It interfaces to the digital readout system via analogue signal transmission. The horizontal integration of FlashCam is expected not only to be more cost efficient, it also allows PDPs with different types of photon detectors to be adapted to the FlashCam readout system. By now, a 144-pixel mini-camera" setup, fully equipped with photomultipliers, PDP electronics, and digitization/ trigger electronics, has been realized and extensively tested. Preparations for a full-scale, 1764 pixel camera mechanics and a cooling system are ongoing. The paper describes the status of the project.

  1. Functionally Redundant RXLR Effectors from Phytophthora infestans Act at Different Steps to Suppress Early flg22-Triggered Immunity

    PubMed Central

    Fraiture, Malou; Liu, Xiaoyu; Boevink, Petra C.; Gilroy, Eleanor M.; Chen, Ying; Kandel, Kabindra; Sessa, Guido; Birch, Paul R. J.; Brunner, Frédéric

    2014-01-01

    Genome sequences of several economically important phytopathogenic oomycetes have revealed the presence of large families of so-called RXLR effectors. Functional screens have identified RXLR effector repertoires that either compromise or induce plant defense responses. However, limited information is available about the molecular mechanisms underlying the modes of action of these effectors in planta. The perception of highly conserved pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs), such as flg22, triggers converging signaling pathways recruiting MAP kinase cascades and inducing transcriptional re-programming, yielding a generic anti-microbial response. We used a highly synchronizable, pathogen-free protoplast-based assay to identify a set of RXLR effectors from Phytophthora infestans (PiRXLRs), the causal agent of potato and tomato light blight that manipulate early stages of flg22-triggered signaling. Of thirty-three tested PiRXLR effector candidates, eight, called Suppressor of early Flg22-induced Immune response (SFI), significantly suppressed flg22-dependent activation of a reporter gene under control of a typical MAMP-inducible promoter (pFRK1-Luc) in tomato protoplasts. We extended our analysis to Arabidopsis thaliana, a non-host plant species of P. infestans. From the aforementioned eight SFI effectors, three appeared to share similar functions in both Arabidopsis and tomato by suppressing transcriptional activation of flg22-induced marker genes downstream of post-translational MAP kinase activation. A further three effectors interfere with MAMP signaling at, or upstream of, the MAP kinase cascade in tomato, but not in Arabidopsis. Transient expression of the SFI effectors in Nicotiana benthamiana enhances susceptibility to P. infestans and, for the most potent effector, SFI1, nuclear localization is required for both suppression of MAMP signaling and virulence function. The present study provides a framework to decipher the molecular mechanisms underlying the manipulation of host MAMP-triggered immunity (MTI) by P. infestans and to understand the basis of host versus non-host resistance in plants towards P. infestans. PMID:24763622

  2. siRNAs and piRNAs Collaborate for Transposon Control in the Two-Spotted Spider Mite.

    PubMed

    Mondal, Mosharrof; Mansfield, Kody; Flynt, Alex

    2018-04-20

    RNAi has revolutionized genetic research, and is being commercialized as an insect pest control technology. Mechanisms exploited for this purpose are antiviral and therefore rapidly evolving. Ideally, RNAi will also be used for non-insect pests, however, differences in RNAi biology makes this uncertain. Tetranychus urticae (two-spotted spider mite) is a destructive non-insect pest, which has a proclivity to develop pesticide resistance. Here we provide a comprehensive study of the endogenous RNAi pathways of spider mites to inform design of exogenous RNAi triggers. This effort revealed unexpected roles for small RNAs and novel genome surveillance pathways. Spider mites have an expanded RNAi machinery relative to insects, encoding RNA dependent RNA polymerase (Rdrp) and extra Piwi-class effectors. Through analyzing T. urticae transcriptome data we explored small RNA biogenesis, and discovered five siRNA loci that appear central to genome surveillance. These RNAs are expressed in the gonad, which we hypothesize to trigger production of piRNAs for control of transposable elements (TEs). This work highlights the need to investigate endogenous RNAi biology as lessons from model organisms may not hold in other species, impacting development of an RNAi strategy. Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  3. Polycystin-2-dependent control of cardiomyocyte autophagy.

    PubMed

    Criollo, Alfredo; Altamirano, Francisco; Pedrozo, Zully; Schiattarella, Gabriele G; Li, Dan L; Rivera-Mejías, Pablo; Sotomayor-Flores, Cristian; Parra, Valentina; Villalobos, Elisa; Battiprolu, Pavan K; Jiang, Nan; May, Herman I; Morselli, Eugenia; Somlo, Stefan; de Smedt, Humbert; Gillette, Thomas G; Lavandero, Sergio; Hill, Joseph A

    2018-05-01

    Considerable evidence points to critical roles of intracellular Ca 2+ homeostasis in the modulation and control of autophagic activity. Yet, underlying molecular mechanisms remain unknown. Mutations in the gene (pkd2) encoding polycystin-2 (PC2) are associated with autosomal dominant polycystic kidney disease (ADPKD), the most common inherited nephropathy. PC2 has been associated with impaired Ca 2+ handling in cardiomyocytes and indirect evidence suggests that this protein may be involved in autophagic control. Here, we investigated the role for PC2 as an essential regulator of Ca 2+ homeostasis and autophagy. Activation of autophagic flux triggered by mTOR inhibition either pharmacologically (rapamycin) or by means of nutrient depletion was suppressed in cells depleted of PC2. Moreover, cardiomyocyte-specific PC2 knockout mice (αMhc-cre;Pkd2 F/F mice) manifested impaired autophagic flux in the setting of nutrient deprivation. Stress-induced autophagy was blunted by intracellular Ca 2+ chelation using BAPTA-AM, whereas removal of extracellular Ca 2+ had no effect, pointing to a role of intracellular Ca 2+ homeostasis in stress-induced cardiomyocyte autophagy. To determine the link between stress-induced autophagy and PC2-induced Ca 2+ mobilization, we over-expressed either wild-type PC2 (WT) or a Ca 2+ -channel deficient PC2 mutant (PC2-D509V). PC2 over-expression increased autophagic flux, whereas PC2-D509V expression did not. Importantly, autophagy induction triggered by PC2 over-expression was attenuated by BAPTA-AM, supporting a model of PC2-dependent control of autophagy through intracellular Ca 2+ . Furthermore, PC2 ablation was associated with impaired Ca 2+ handling in cardiomyocytes marked by partial depletion of sarcoplasmic reticulum Ca 2+ stores. Finally, we provide evidence that Ca 2+ -mediated autophagy elicited by PC2 is a mechanism conserved across multiple cell types. Together, this study unveils PC2 as a novel regulator of autophagy acting through control of intracellular Ca 2+ homeostasis. Copyright © 2018. Published by Elsevier Ltd.

  4. An NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles for tumor targeted drug delivery in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Gayam, Srivardhan Reddy; Venkatesan, Parthiban; Sung, Yi-Ming; Sung, Shuo-Yuan; Hu, Shang-Hsiu; Hsu, Hsin-Yun; Wu, Shu-Pao

    2016-06-01

    The synthesis and characterization of an NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles (MSNPs) for on-command delivery applications has been described in this paper. Gatekeeping of MSNPs is achieved by the integration of mechanically interlocked rotaxane nanovalves on the surface of MSNPs. The rotaxane nanovalve system is composed of a linear stalk anchoring on the surface of MSNPs, an α-cyclodextrin ring that encircles it and locks the payload ``cargo'' molecules in the mesopores, and a benzoquinone stopper incorporated at the end of the stalk. The gate opening and controlled release of the cargo are triggered by cleavage of the benzoquinone stopper using an endogenous NQO1 enzyme. In addition to having efficient drug loading and controlled release mechanisms, this smart biocompatible carrier system showed obvious uptake and consequent release of the drug in tumor cells, could selectively induce the tumor cell death and enhance the capability of inhibition of tumor growth in vivo. The controlled drug delivery system demonstrated its use as a potential theranostic material.The synthesis and characterization of an NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles (MSNPs) for on-command delivery applications has been described in this paper. Gatekeeping of MSNPs is achieved by the integration of mechanically interlocked rotaxane nanovalves on the surface of MSNPs. The rotaxane nanovalve system is composed of a linear stalk anchoring on the surface of MSNPs, an α-cyclodextrin ring that encircles it and locks the payload ``cargo'' molecules in the mesopores, and a benzoquinone stopper incorporated at the end of the stalk. The gate opening and controlled release of the cargo are triggered by cleavage of the benzoquinone stopper using an endogenous NQO1 enzyme. In addition to having efficient drug loading and controlled release mechanisms, this smart biocompatible carrier system showed obvious uptake and consequent release of the drug in tumor cells, could selectively induce the tumor cell death and enhance the capability of inhibition of tumor growth in vivo. The controlled drug delivery system demonstrated its use as a potential theranostic material. Electronic supplementary information (ESI) available: Synthesis and characterization of the functional molecules and MSNPs is available in the ESI. See DOI: 10.1039/c6nr03525f

  5. Modeling the roles of damage accumulation and mechanical healing on rainfall-induced landslides

    NASA Astrophysics Data System (ADS)

    Fan, Linfeng; Lehmann, Peter; Or, Dani

    2014-05-01

    The abrupt release of rainfall-induced shallow landslides is preceded by local failures that may abruptly coalesce and form a continuous failure plane within a hillslope. The mechanical status of hillslopes reflects a competition between the extent of severity of accumulated local damage during prior rainfall events and the rates of mechanically healing (i.e. regaining of strength) by closure of micro-cracks, regrowth of roots, etc. The interplay of these processes affects the initial conditions for landslide modeling and shapes potential failure patterns during future rainfall events. We incorporated these competing mechanical processes in a hydro-mechanical landslide triggering model subjected to a sequence of rainfall scenarios. The model employs the Fiber Bundle Model (FBM) with bonds (fiber bundle) with prescribed threshold linking adjacent soil columns and soil to bedrock. Prior damage was represented by a fraction of broken fibers during previous rainfall events, and the healing of broken fibers was described by strength regaining models for soil and roots at different characteristic time scales. Results show that prior damage and healing introduce highly nonlinear response to landslide triggering. For small prior damage, mechanical bonds at soil-bedrock interface may fail early in next rainfall event but lead to small perturbations onto lateral bonds without triggering a landslide. For more severe damage weakening lateral bonds, excess load due to failure at soil-bedrock interface accumulates at downslope soil columns resulting in early soil failure with patterns strongly correlated with prior damage distribution. Increasing prior damage over the hillslope decreases the volume of first landslide and prolongs the time needed to trigger the second landslide due to mechanical relaxation of the system. The mechanical healing of fibers diminishes effects of prior damage on the time of failure, and shortens waiting time between the first and second landslides. These findings highlight the need to improve definition of initial conditions and the shortcomings of assuming pristine hillslopes.

  6. Dehydration-driven stress transfer triggers intermediate-depth earthquakes

    PubMed Central

    Ferrand, Thomas P.; Hilairet, Nadège; Incel, Sarah; Deldicque, Damien; Labrousse, Loïc; Gasc, Julien; Renner, Joerg; Wang, Yanbin; Green II, Harry W.; Schubnel, Alexandre

    2017-01-01

    Intermediate-depth earthquakes (30–300 km) have been extensively documented within subducting oceanic slabs, but their mechanics remains enigmatic. Here we decipher the mechanism of these earthquakes by performing deformation experiments on dehydrating serpentinized peridotites (synthetic antigorite-olivine aggregates, minerals representative of subduction zones lithologies) at upper mantle conditions. At a pressure of 1.1 gigapascals, dehydration of deforming samples containing only 5 vol% of antigorite suffices to trigger acoustic emissions, a laboratory-scale analogue of earthquakes. At 3.5 gigapascals, acoustic emissions are recorded from samples with up to 50 vol% of antigorite. Experimentally produced faults, observed post-mortem, are sealed by fluid-bearing micro-pseudotachylytes. Microstructural observations demonstrate that antigorite dehydration triggered dynamic shear failure of the olivine load-bearing network. These laboratory analogues of intermediate-depth earthquakes demonstrate that little dehydration is required to trigger embrittlement. We propose an alternative model to dehydration-embrittlement in which dehydration-driven stress transfer, rather than fluid overpressure, causes embrittlement. PMID:28504263

  7. Engineering a pH-Regulated Switch in the Major Light-Harvesting Complex of Plants (LHCII): Proof of Principle.

    PubMed

    Liguori, Nicoletta; Natali, Alberto; Croce, Roberta

    2016-12-15

    Under excess light, photosynthetic organisms employ feedback mechanisms to avoid photodamage. Photoprotection is triggered by acidification of the lumen of the photosynthetic membrane following saturation of the metabolic activity. A low pH triggers thermal dissipation of excess absorbed energy by the light-harvesting complexes (LHCs). LHCs are not able to sense pH variations, and their switch to a dissipative mode depends on stress-related proteins and allosteric cofactors. In green algae the trigger is the pigment-protein complex LHCSR3. Its C-terminus is responsible for a pH-driven conformational change from a light-harvesting to a quenched state. Here, we show that by replacing the C-terminus of the main LHC of plants with that of LHCSR3, it is possible to regulate its excited-state lifetime solely via protonation, demonstrating that the protein template of LHCs can be modified to activate reversible quenching mechanisms independent of external cofactors and triggers.

  8. Dehydration-driven stress transfer triggers intermediate-depth earthquakes

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

    Ferrand, Thomas P.; Hilairet, Nadège; Incel, Sarah

    Intermediate-depth earthquakes (30–300 km) have been extensively documented within subducting oceanic slabs, but their mechanics remains enigmatic. Here in this paper we decipher the mechanism of these earthquakes by performing deformation experiments on dehydrating serpentinized peridotites (synthetic antigorite-olivine aggregates, minerals representative of subduction zones lithologies) at upper mantle conditions. At a pressure of 1.1 gigapascals, dehydration of deforming samples containing only 5 vol% of antigorite suffices to trigger acoustic emissions, a laboratory-scale analogue of earthquakes. At 3.5 gigapascals, acoustic emissions are recorded from samples with up to 50 vol% of antigorite. Experimentally produced faults, observed post-mortem, are sealed by fluid-bearingmore » micro-pseudotachylytes. Microstructural observations demonstrate that antigorite dehydration triggered dynamic shear failure of the olivine load-bearing network. These laboratory analogues of intermediatedepth earthquakes demonstrate that little dehydration is required to trigger embrittlement. We propose an alternative model to dehydration-embrittlement in which dehydration-driven stress transfer, rather than fluid overpressure, causes embrittlement.« less

  9. Dehydration-driven stress transfer triggers intermediate-depth earthquakes

    DOE PAGES

    Ferrand, Thomas P.; Hilairet, Nadège; Incel, Sarah; ...

    2017-05-15

    Intermediate-depth earthquakes (30–300 km) have been extensively documented within subducting oceanic slabs, but their mechanics remains enigmatic. Here in this paper we decipher the mechanism of these earthquakes by performing deformation experiments on dehydrating serpentinized peridotites (synthetic antigorite-olivine aggregates, minerals representative of subduction zones lithologies) at upper mantle conditions. At a pressure of 1.1 gigapascals, dehydration of deforming samples containing only 5 vol% of antigorite suffices to trigger acoustic emissions, a laboratory-scale analogue of earthquakes. At 3.5 gigapascals, acoustic emissions are recorded from samples with up to 50 vol% of antigorite. Experimentally produced faults, observed post-mortem, are sealed by fluid-bearingmore » micro-pseudotachylytes. Microstructural observations demonstrate that antigorite dehydration triggered dynamic shear failure of the olivine load-bearing network. These laboratory analogues of intermediatedepth earthquakes demonstrate that little dehydration is required to trigger embrittlement. We propose an alternative model to dehydration-embrittlement in which dehydration-driven stress transfer, rather than fluid overpressure, causes embrittlement.« less

  10. Flower abscission in Vitis vinifera L. triggered by gibberellic acid and shade discloses differences in the underlying metabolic pathways

    PubMed Central

    Domingos, Sara; Scafidi, Pietro; Cardoso, Vania; Leitao, Antonio E.; Di Lorenzo, Rosario; Oliveira, Cristina M.; Goulao, Luis F.

    2015-01-01

    Understanding abscission is both a biological and an agronomic challenge. Flower abscission induced independently by shade and gibberellic acid (GAc) sprays was monitored in grapevine (Vitis vinifera L.) growing under a soilless greenhouse system during two seasonal growing conditions, in an early and late production cycle. Physiological and metabolic changes triggered by each of the two distinct stimuli were determined. Environmental conditions exerted a significant effect on fruit set as showed by the higher natural drop rate recorded in the late production cycle with respect to the early cycle. Shade and GAc treatments increased the percentage of flower drop compared to the control, and at a similar degree, during the late production cycle. The reduction of leaf gas exchanges under shade conditions was not observed in GAc treated vines. The metabolic profile assessed in samples collected during the late cycle differently affected primary and secondary metabolisms and showed that most of the treatment-resulting variations occurred in opposite trends in inflorescences unbalanced in either hormonal or energy deficit abscission-inducing signals. Particularly concerning carbohydrates metabolism, sucrose, glucose, tricarboxylic acid metabolites and intermediates of the raffinose family oligosaccharides pathway were lower in shaded and higher in GAc samples. Altered oxidative stress remediation mechanisms and indolacetic acid (IAA) concentration were identified as abscission signatures common to both stimuli. According to the global analysis performed, we report that grape flower abscission mechanisms triggered by GAc application and C-starvation are not based on the same metabolic pathways. PMID:26157448

  11. Security Implications of Induced Earthquakes

    NASA Astrophysics Data System (ADS)

    Jha, B.; Rao, A.

    2016-12-01

    The increase in earthquakes induced or triggered by human activities motivates us to research how a malicious entity could weaponize earthquakes to cause damage. Specifically, we explore the feasibility of controlling the location, timing and magnitude of an earthquake by activating a fault via injection and production of fluids into the subsurface. Here, we investigate the relationship between the magnitude and trigger time of an induced earthquake to the well-to-fault distance. The relationship between magnitude and distance is important to determine the farthest striking distance from which one could intentionally activate a fault to cause certain level of damage. We use our novel computational framework to model the coupled multi-physics processes of fluid flow and fault poromechanics. We use synthetic models representative of the New Madrid Seismic Zone and the San Andreas Fault Zone to assess the risk in the continental US. We fix injection and production flow rates of the wells and vary their locations. We simulate injection-induced Coulomb destabilization of faults and evolution of fault slip under quasi-static deformation. We find that the effect of distance on the magnitude and trigger time is monotonic, nonlinear, and time-dependent. Evolution of the maximum Coulomb stress on the fault provides insights into the effect of the distance on rupture nucleation and propagation. The damage potential of induced earthquakes can be maintained even at longer distances because of the balance between pressure diffusion and poroelastic stress transfer mechanisms. We conclude that computational modeling of induced earthquakes allows us to measure feasibility of weaponzing earthquakes and developing effective defense mechanisms against such attacks.

  12. A novel approach to periodic event-triggered control: Design and application to the inverted pendulum.

    PubMed

    Aranda-Escolástico, Ernesto; Guinaldo, María; Gordillo, Francisco; Dormido, Sebastián

    2016-11-01

    In this paper, periodic event-triggered controllers are proposed for the rotary inverted pendulum. The control strategy is divided in two steps: swing-up and stabilization. In both cases, the system is sampled periodically but the control actions are only computed at certain instances of time (based on events), which are a subset of the sampling times. For the stabilization control, the asymptotic stability is guaranteed applying the Lyapunov-Razumikhin theorem for systems with delays. This result is applicable to general linear systems and not only to the inverted pendulum. For the swing-up control, a trigger function is provided from the derivative of the Lyapunov function for the swing-up control law. Experimental results show a significant improvement with respect to periodic control in the number of control actions. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

  13. An alternative laser driven photodissociation mechanism of pyrrole via πσ*1∕S0 conical intersection.

    PubMed

    Nandipati, K R; Lan, Z; Singh, H; Mahapatra, S

    2017-06-07

    A first principles quantum dynamics study of N-H photodissociation of pyrrole on the S 0 - 1 πσ * (A21) coupled electronic states is carried out with the aid of an optimally designed UV-laser pulse. A new photodissociation path, as compared to the conventional barrier crossing on the πσ*1 state, opens up upon electronic transitions under the influence of pump-dump laser pulses, which efficiently populate both the dissociation channels. The interplay of electronic transitions due both to vibronic coupling and the laser pulse is observed in the control mechanism and discussed in detail. The proposed control mechanism seems to be robust, and not discussed in the literature so far, and is expected to trigger future experiments on the πσ*1 photochemistry of molecules of chemical and biological importance. The design of the optimal pulses and their application to enhance the overall dissociation probability is carried out within the framework of optimal control theory. The quantum dynamics of the system in the presence of pulse is treated by solving the time-dependent Schrödinger equation in the semi-classical dipole approximation.

  14. An alternative laser driven photodissociation mechanism of pyrrole via πσ*1∕S0 conical intersection

    PubMed Central

    Nandipati, K. R.; Lan, Z.; Singh, H.; Mahapatra, S.

    2017-01-01

    A first principles quantum dynamics study of N–H photodissociation of pyrrole on the S0−1πσ*(A21) coupled electronic states is carried out with the aid of an optimally designed UV-laser pulse. A new photodissociation path, as compared to the conventional barrier crossing on the πσ*1 state, opens up upon electronic transitions under the influence of pump-dump laser pulses, which efficiently populate both the dissociation channels. The interplay of electronic transitions due both to vibronic coupling and the laser pulse is observed in the control mechanism and discussed in detail. The proposed control mechanism seems to be robust, and not discussed in the literature so far, and is expected to trigger future experiments on the πσ*1 photochemistry of molecules of chemical and biological importance. The design of the optimal pulses and their application to enhance the overall dissociation probability is carried out within the framework of optimal control theory. The quantum dynamics of the system in the presence of pulse is treated by solving the time-dependent Schrödinger equation in the semi-classical dipole approximation. PMID:28595406

  15. An alternative laser driven photodissociation mechanism of pyrrole via π*1σ/S0 conical intersection

    NASA Astrophysics Data System (ADS)

    Nandipati, K. R.; Lan, Z.; Singh, H.; Mahapatra, S.

    2017-06-01

    A first principles quantum dynamics study of N-H photodissociation of pyrrole on the S0-1π σ*(A12) coupled electronic states is carried out with the aid of an optimally designed UV-laser pulse. A new photodissociation path, as compared to the conventional barrier crossing on the π*1σ state, opens up upon electronic transitions under the influence of pump-dump laser pulses, which efficiently populate both the dissociation channels. The interplay of electronic transitions due both to vibronic coupling and the laser pulse is observed in the control mechanism and discussed in detail. The proposed control mechanism seems to be robust, and not discussed in the literature so far, and is expected to trigger future experiments on the π*1σ photochemistry of molecules of chemical and biological importance. The design of the optimal pulses and their application to enhance the overall dissociation probability is carried out within the framework of optimal control theory. The quantum dynamics of the system in the presence of pulse is treated by solving the time-dependent Schrödinger equation in the semi-classical dipole approximation.

  16. Dual triggering with GnRH agonist plus hCG versus triggering with hCG alone for IVF/ICSI outcome in GnRH antagonist cycles: a systematic review and meta-analysis.

    PubMed

    Chen, Chi-Huang; Tzeng, Chii-Ruey; Wang, Peng-Hui; Liu, Wei-Min; Chang, Heng-Yu; Chen, Huang-Hui; Chen, Ching-Hui

    2018-03-29

    To summarize available evidence from randomized-controlled trials which have evaluated triggering of final oocyte maturation with concomitant GnRH agonists and hCG in patients undergoing IVF, and to analyze whether dual triggering is as efficacious as hCG triggering in terms of oocyte and pregnancy outcomes. A comprehensive literature search was performed to identify randomized-controlled trials comparing IVF outcomes between women receiving combined administration of hCG with GnRH agonists and those receiving hCG alone for triggering of final oocyte maturation. Four studies including 527 patients eligible for inclusion in meta-analysis were identified. No significant difference in the number of mature oocytes or fertilized oocytes retrieved was found between groups. Clinical pregnancy rate with dual triggering was significantly higher as compared with hCG-alone triggering (pooled OR = 0.48, 95% CI 0.31-0.77, P = 0.002), but there was no significant difference in the ongoing pregnancy rate between groups. Results of meta-analysis indicate comparable or significantly improved outcomes with the use of GnRH agonists plus hCG as compared with hCG alone for triggering of final oocyte maturation.

  17. Downregulation of MicroRNA miR-526a by Enterovirus Inhibits RIG-I-Dependent Innate Immune Response

    PubMed Central

    Xu, Changzhi; He, Xiang; Zheng, Zirui; Zhang, Zhe; Wei, Congwen; Guan, Kai; Hou, Lihua; Zhang, Buchang; Zhu, Lin; Cao, Yuan; Zhang, Yanhong; Cao, Ye; Ma, Shengli; Wang, Penghao; Zhang, Pingping; Xu, Quanbin; Ling, Youguo

    2014-01-01

    ABSTRACT Retinoic acid-inducible gene I (RIG-I) is an intracellular RNA virus sensor that induces type I interferon-mediated host-protective innate immunity against viral infection. Although cylindromatosis (CYLD) has been shown to negatively regulate innate antiviral response by removing K-63-linked polyubiquitin from RIG-I, the regulation of its expression and the underlying regulatory mechanisms are still incompletely understood. Here we show that RIG-I activity is regulated by inhibition of CYLD expression mediated by the microRNA miR-526a. We found that viral infection specifically upregulates miR-526a expression in macrophages via interferon regulatory factor (IRF)-dependent mechanisms. In turn, miR-526a positively regulates virus-triggered type I interferon (IFN-I) production, thus suppressing viral replication, the underlying mechanism of which is the enhancement of RIG-I K63-linked ubiquitination by miR-526a via suppression of the expression of CYLD. Remarkably, virus-induced miR-526a upregulation and CYLD downregulation are blocked by enterovirus 71 (EV71) 3C protein, while ectopic miR-526a expression inhibits the replication of EV71 virus. The collective results of this study suggest a novel mechanism of the regulation of RIG-I activity during RNA virus infection by miR-526a and suggest a novel mechanism for the evasion of the innate immune response controlled by EV71. IMPORTANCE RNA virus infection upregulates the expression of miR-526a in macrophages through IRF-dependent pathways. In turn, miR-526a positively regulates virus-triggered type I IFN production and inhibits viral replication, the underlying mechanism of which is the enhancement of RIG-I K-63 ubiquitination by miR-526a via suppression of the expression of CYLD. Remarkably, virus-induced miR-526a upregulation and CYLD downregulation are blocked by enterovirus 71 (EV71) 3C protein; cells with overexpressed miR-526a were highly resistant to EV71 infection. The collective results of this study suggest a novel mechanism of the regulation of RIG-I activity during RNA virus infection by miR-526a and propose a novel mechanism for the evasion of the innate immune response controlled by EV71. PMID:25056901

  18. An illness-specific version of the Revised Illness Perception Questionnaire in patients with atrial fibrillation (AF IPQ-R): Unpacking beliefs about treatment control, personal control and symptom triggers.

    PubMed

    Taylor, Elaina C; O'Neill, Mark; Hughes, Lyndsay D; Moss-Morris, Rona

    2018-04-01

    This study modified the Revised Illness Perception Questionnaire (IPQ-R) in patients with persistent atrial fibrillation (AF). Qualitative interviews and think-aloud techniques informed modification of the IPQ-R to be specific to AF patients. Confirmatory Factor Analysis (CFA) (n = 198) examined the validity of the modified IPQ-R (AF-IPQ-R). Exploratory factor analysis (EFA) examined the new AF-triggers scale. Construct validity examined associations between the AF-IPQ-R, quality of life (QoL) and beliefs about medicines. Test-retest and internal reliability were examined. Interviews indicated that patients viewed triggers of AF rather than initial causes of illness as more applicable. Patients believed specific behaviours such as rest could control AF. Treatment control beliefs related to pharmacological and procedural treatments. These data were used to modify the IPQ-R subscales and to develop a triggers of AF scale. CFA indicated good model fit. EFA of the triggers scale indicated three factors: emotional; health behaviours; and over-exertion triggers. Expected correlations were found between the AF-IPQ-R, QoL and treatment beliefs, evidencing good construct validity. The AF-IPQ-R showed sound psychometric properties. It provides more detailed specification than the IPQ-R of beliefs that may help to understand poor QoL in AF patients, and guidance for future interventions in this area.

  19. Food and symptom generation in functional gastrointestinal disorders: physiological aspects.

    PubMed

    Farré, Ricard; Tack, Jan

    2013-05-01

    The response of the gastrointestinal tract (GIT) to ingestion of food is a complex and closely controlled process, which allows optimization of propulsion, digestion, absorption of nutrients, and removal of indigestible remnants. This review summarizes current knowledge on the mechanisms that control the response of the GIT to food intake. During the cephalic phase, triggered by cortical food-related influences, the GIT prepares for receiving nutrients. The gastric phase is dominated by the mechanical effect of the meal volume. Accumulation of food in the stomach activates tension-sensitive mechanoreceptors, which in turn stimulate gastric accommodation and gastric acid secretion through the intrinsic and vago-vagal reflex pathways. After meal ingestion, the tightly controlled process of gastric emptying starts, with arrival of nutrients in the duodenum triggering negative feedback on emptying and stimulating secretion of digestive enzymes through the neural (mainly vago-vagal reflex, but also intrinsic) and endocrine (release of peptides from entero-endocrine cells) pathways. Several types of specialized receptors detect the presence of all main categories of nutrients. In addition, the gastrointestinal mucosa expresses receptors of the T1R and T2R families (taste receptors) and several members of the transient receptor potential channel family, all of which are putatively involved in the detection of specific tastants in the lumen. Activation of nutrient and taste sensors also activates the extrinsic and intrinsic neural, as well as entero-endocrine, pathways. During passage through the small bowel, nutrients are progressively extracted, and electrolyte-rich liquid intestinal content with non-digestible residue is delivered to the colon. The colon provides absorption of the water and electrolytes, storage of non-digestible remnants of food, aboral propulsion of contents, and finally evacuation through defecation.

  20. Posttranscriptional regulation of adrenal TH gene expression contributes to the maladaptive responses triggered by insulin-induced recurrent hypoglycemia.

    PubMed

    Kudrick, Necla; Chan, Owen; La Gamma, Edmund F; Kim, Juhye Lena; Tank, Arnold William; Sterling, Carol; Nankova, Bistra B

    2015-02-01

    Acute metabolic stress such as insulin-induced hypoglycemia triggers a counterregulatory response during which the release of catecholamines (epinephrine), the activation of tyrosine hydroxylase (TH) enzyme and subsequent compensatory catecholamine biosynthesis occur in the adrenal medulla. However, recurrent exposure to hypoglycemia (RH), a consequence of tight glycemic control in individuals with type 1 and type 2 diabetes compromises this physiological response. The molecular mechanisms underlying the maladaptive response to repeated glucose deprivation are incompletely understood. We hypothesize that impaired epinephrine release following RH reflects altered regulation of adrenal catecholamine biosynthesis. To test this hypothesis, we compared the effect of single daily (RH) and twice-daily episodes of insulin-induced hypoglycemia (2RH) on adrenal epinephrine release and production in normal rats. Control animals received saline injections under similar conditions (RS and 2RS, respectively). Following 3 days of treatment, we assessed the counterregulatory hormonal responses during a hypoglycemic clamp. Changes in adrenal TH gene expression were also analyzed. The counterregulatory responses, relative TH transcription and TH mRNA levels and Ser40-TH phosphorylation (marker for enzyme activation) were induced to a similar extent in RS, 2RS, and RH groups. In contrast, epinephrine and glucagon responses were attenuated in the 2RH group and this was associated with a limited elevation of adrenal TH mRNA, rapid inactivation of TH enzyme and no significant changes in TH protein. Our results suggest that novel posttranscriptional mechanisms controlling TH mRNA and activated TH enzyme turnover contribute to the impaired epinephrine responses and may provide new therapeutic targets to prevent HAAF. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  1. Posttranscriptional regulation of adrenal TH gene expression contributes to the maladaptive responses triggered by insulin-induced recurrent hypoglycemia

    PubMed Central

    Kudrick, Necla; Chan, Owen; La Gamma, Edmund F; Kim, Juhye Lena; Tank, Arnold William; Sterling, Carol; Nankova, Bistra B

    2015-01-01

    Acute metabolic stress such as insulin-induced hypoglycemia triggers a counterregulatory response during which the release of catecholamines (epinephrine), the activation of tyrosine hydroxylase (TH) enzyme and subsequent compensatory catecholamine biosynthesis occur in the adrenal medulla. However, recurrent exposure to hypoglycemia (RH), a consequence of tight glycemic control in individuals with type 1 and type 2 diabetes compromises this physiological response. The molecular mechanisms underlying the maladaptive response to repeated glucose deprivation are incompletely understood. We hypothesize that impaired epinephrine release following RH reflects altered regulation of adrenal catecholamine biosynthesis. To test this hypothesis, we compared the effect of single daily (RH) and twice-daily episodes of insulin-induced hypoglycemia (2RH) on adrenal epinephrine release and production in normal rats. Control animals received saline injections under similar conditions (RS and 2RS, respectively). Following 3 days of treatment, we assessed the counterregulatory hormonal responses during a hypoglycemic clamp. Changes in adrenal TH gene expression were also analyzed. The counterregulatory responses, relative TH transcription and TH mRNA levels and Ser40-TH phosphorylation (marker for enzyme activation) were induced to a similar extent in RS, 2RS, and RH groups. In contrast, epinephrine and glucagon responses were attenuated in the 2RH group and this was associated with a limited elevation of adrenal TH mRNA, rapid inactivation of TH enzyme and no significant changes in TH protein. Our results suggest that novel posttranscriptional mechanisms controlling TH mRNA and activated TH enzyme turnover contribute to the impaired epinephrine responses and may provide new therapeutic targets to prevent HAAF. PMID:25713330

  2. Epigenetic regulation of serotype expression antagonizes transcriptome dynamics in Paramecium tetraurelia

    PubMed Central

    Cheaib, Miriam; Dehghani Amirabad, Azim; Nordström, Karl J. V.; Schulz, Marcel H.; Simon, Martin

    2015-01-01

    Phenotypic variation of a single genotype is achieved by alterations in gene expression patterns. Regulation of such alterations depends on their time scale, where short-time adaptations differ from permanently established gene expression patterns maintained by epigenetic mechanisms. In the ciliate Paramecium, serotypes were described for an epigenetically controlled gene expression pattern of an individual multigene family. Paradoxically, individual serotypes can be triggered in Paramecium by alternating environments but are then stabilized by epigenetic mechanisms, thus raising the question to which extend their expression follows environmental stimuli. To characterize environmental adaptation in the context of epigenetically controlled serotype expression, we used RNA-seq to characterize transcriptomes of serotype pure cultures. The resulting vegetative transcriptome resource is first analysed for genes involved in the adaptive response to the altered environment. Secondly, we identified groups of genes that do not follow the adaptive response but show co-regulation with the epigenetically controlled serotype system, suggesting that their gene expression pattern becomes manifested by similar mechanisms. In our experimental set-up, serotype expression and the entire group of co-regulated genes were stable among environmental changes and only heat-shock genes altered expression of these gene groups. The data suggest that the maintenance of these gene expression patterns in a lineage represents epigenetically controlled robustness counteracting short-time adaptation processes. PMID:26231545

  3. A Note on Inconsistent Axioms in Rushby's Systematic Formal Verification for Fault-Tolerant Time-Triggered Algorithms

    NASA Technical Reports Server (NTRS)

    Pike, Lee

    2005-01-01

    I describe some inconsistencies in John Rushby s axiomatization of time-triggered algorithms that he presents in these transactions and that he formally specifies and verifies in a mechanical theorem-prover. I also present corrections for these inconsistencies.

  4. Identifying Potential Ventilator Auto-Triggering Among Organ Procurement Organization Referrals.

    PubMed

    Henry, Nicholas R; Russian, Christopher J; Nespral, Joseph

    2016-06-01

    Ventilator auto-trigger is the delivery of an assisted mechanical ventilated breath over the set ventilator frequency in the absence of a spontaneous inspiratory effort and can be caused by inappropriate ventilator trigger sensitivity. Ventilator auto-trigger can be misinterpreted as a spontaneous breath and has the potential to delay or prevent brain death testing and confuse health-care professionals and/or patient families. To determine the frequency of organ donor referrals from 1 Organ Procurement Organization (OPO) that could benefit from an algorithm designed to assist organ recovery coordinators to identify and correct ventilator auto-triggering. This retrospective analysis evaluated documentation of organ donor referrals from 1 OPO in central Texas during the 2013 calendar year that resulted in the withdrawal of care by the patient's family and the recovery of organs. The frequency of referrals that presented with absent brain stem reflexes except for additional respirations over the set ventilator rate was determined to assess for the need of the proposed algorithm. Documentation of 672 organ procurement organization referrals was evaluated. Documentation from 42 referrals that resulted in the withdrawal of care and 21 referrals that resulted in the recovery of organs were identified with absent brain stem reflexes except for spontaneous respirations on the mechanical ventilator. As a result, an algorithm designed to identify and correct ventilator auto-trigger could have been used 63 times during the 2013 calendar year. © 2016, NATCO.

  5. [Anesthesia unrelated triggering of a fatal malignant hyperthermia crisis].

    PubMed

    Olthoff, D; Vonderlind, C

    1997-12-01

    For incidents of malignant hyperthermia (MH) outside the hospital, a high number of unrecorded cases must be reckoned with because of an insufficient knowledge of emergency services and poor identification and documentation that make it impossible to classify acute situations under the diagnosis of malignant hyperthermia crisis. As a result, there are no statistical data in this field, and only case reports with a broad spectrum of suspected trigger mechanisms have been published. The case described in this report is a proved example of a non-anesthesia-related triggering of MH in a 21-year-old man who had had an anesthetic-induced MH manifestation in childhood, which was confirmed with an in vitro contracture test. After visiting a restaurant, he became unconscious and convulsive after consuming a high level of alcohol (2.9/1000). The first cardiocirculatory arrest occurred directly before hospitalization. After admission, the patient showed a full-blown MH episode whose subsequent fatality was unavoidable in spite of adapted and optimal therapy. Suspected trigger mechanisms seem to be multifactoral (excessive alcohol consumption, over-heating, mental stress) as a forensic investigation did not point to any particular signs of typical trigger substances. The case demonstrates again that an MH attack might be triggered under certain non-anaesthesia-related situations. For patients with an MH disposition, additional information on their behavior outside the hospital is required.

  6. Hit-and-run stimulation: a novel concept to reactivate latent HIV-1 infection without cytokine gene induction.

    PubMed

    Wolschendorf, Frank; Duverger, Alexandra; Jones, Jennifer; Wagner, Frederic H; Huff, Jason; Benjamin, William H; Saag, Michael S; Niederweis, Michael; Kutsch, Olaf

    2010-09-01

    Current antiretroviral therapy (ART) efficiently controls HIV-1 replication but fails to eradicate the virus. Even after years of successful ART, HIV-1 can conceal itself in a latent state in long-lived CD4(+) memory T cells. From this latent reservoir, HIV-1 rebounds during treatment interruptions. Attempts to therapeutically eradicate this viral reservoir have yielded disappointing results. A major problem with previously utilized activating agents is that at the concentrations required for efficient HIV-1 reactivation, these stimuli trigger high-level cytokine gene expression (hypercytokinemia). Therapeutically relevant HIV-1-reactivating agents will have to trigger HIV-1 reactivation without the induction of cytokine expression. We present here a proof-of-principle study showing that this is a possibility. In a high-throughput screening effort, we identified an HIV-1-reactivating protein factor (HRF) secreted by the nonpathogenic bacterium Massilia timonae. In primary T cells and T-cell lines, HRF triggered a high but nonsustained peak of nuclear factor kappa B (NF-kappaB) activity. While this short NF-kappaB peak potently reactivated latent HIV-1 infection, it failed to induce gene expression of several proinflammatory NF-kappaB-dependent cellular genes, such as those for tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), and gamma interferon (IFN-gamma). Dissociation of cellular and viral gene induction was achievable, as minimum amounts of Tat protein, synthesized following application of a short NF-kappaB pulse, triggered HIV-1 transactivation and subsequent self-perpetuated HIV-1 expression. In the absence of such a positive feedback mechanism, cellular gene expression was not sustained, suggesting that strategies modulating the NF-kappaB activity profile could be used to selectively trigger HIV-1 reactivation.

  7. Viruses, Artificial Viruses and Virus-Based Structures for Biomedical Applications.

    PubMed

    van Rijn, Patrick; Schirhagl, Romana

    2016-06-01

    Nanobiomaterials such as virus particles and artificial virus particles offer tremendous opportunities to develop new biomedical applications such as drug- or gene-delivery, imaging and sensing but also improve understanding of biological mechanisms. Recent advances within the field of virus-based systems give insights in how to mimic viral structures and virus assembly processes as well as understanding biodistribution, cell/tissue targeting, controlled and triggered disassembly or release and circulation times. All these factors are of high importance for virus-based functional systems. This review illustrates advances in mimicking and enhancing or controlling these aspects to a high degree toward delivery and imaging applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Reflex epileptic mechanisms in humans: Lessons about natural ictogenesis.

    PubMed

    Wolf, Peter

    2017-06-01

    The definition of reflex epileptic seizures is that specific seizure types can be triggered by certain sensory or cognitive stimuli. Simple triggers are sensory (most often visual, more rarely tactile or proprioceptive; simple audiogenic triggers in humans are practically nonexistent) and act within seconds, whereas complex triggers like praxis, reading and talking, and music are mostly cognitive and work within minutes. The constant relation between a qualitatively, often even quantitatively, well-defined stimulus and a specific epileptic response provides unique possibilities to investigate seizure generation in natural human epilepsies. For several reflex epileptic mechanisms (REMs), this has been done. Reflex epileptic mechanisms have been reported less often in focal lesional epilepsies than in idiopathic "generalized" epilepsies (IGEs) which are primarily genetically determined. The key syndrome of IGE is juvenile myoclonic epilepsy (JME), where more than half of the patients present reflex epileptic traits (photosensitivity, eye closure sensitivity, praxis induction, and language-induced orofacial reflex myocloni). Findings with multimodal investigations of cerebral function concur to indicate that ictogenic mechanisms in IGEs largely (ab)use preexisting functional anatomic networks (CNS subsystems) normally serving highly complex physiological functions (e.g., deliberate complex actions and linguistic communication) which supports the concept of system epilepsy. Whereas REMs in IGEs, thus, are primarily function-related, in focal epilepsies, they are primarily localization-related. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Isoform-selective regulation of glycogen phosphorylase by energy deprivation and phosphorylation in astrocytes.

    PubMed

    Müller, Margit S; Pedersen, Sofie E; Walls, Anne B; Waagepetersen, Helle S; Bak, Lasse K

    2015-01-01

    Glycogen phosphorylase (GP) is activated to degrade glycogen in response to different stimuli, to support both the astrocyte's own metabolic demand and the metabolic needs of neurons. The regulatory mechanism allowing such a glycogenolytic response to distinct triggers remains incompletely understood. In the present study, we used siRNA-mediated differential knockdown of the two isoforms of GP expressed in astrocytes, muscle isoform (GPMM), and brain isoform (GPBB), to analyze isoform-specific regulatory characteristics in a cellular setting. Subsequently, we tested the response of each isoform to phosphorylation, triggered by incubation with norepinephrine (NE), and to AMP, increased by glucose deprivation in cells in which expression of one GP isoform had been silenced. Successful knockdown was demonstrated on the protein level by Western blot, and on a functional level by determination of glycogen content showing an increase in glycogen levels following knockdown of either GPMM or GPBB. NE triggered glycogenolysis within 15 min in control cells and after GPBB knockdown. However, astrocytes in which expression of GPMM had been silenced showed a delay in response to NE, with glycogen levels significantly reduced only after 60 min. In contrast, allosteric activation of GP by AMP, induced by glucose deprivation, seemed to mainly affect GPBB, as only knockdown of GPBB, but not of GPMM, delayed the glycogenolytic response to glucose deprivation. Our results indicate that the two GP isoforms expressed in astrocytes respond to different physiological triggers, therefore conferring distinct metabolic functions of brain glycogen. © 2014 Wiley Periodicals, Inc.

  10. Mechanics of rainfall-induced flow failure in unsaturated shallow slopes (Invited)

    NASA Astrophysics Data System (ADS)

    Buscarnera, G.

    2013-12-01

    The increase in pore water pressure due to rain infiltration can be a dominant component in the activation of slope instabilities. This work shows an application of the theory of material stability to the triggering analysis of this important class of natural hazards. The goal is to identify the mechanisms through which the process of rain infiltration promotes instabilities of the flow-type in the soil covers. The interplay between increase in pore water pressure and failure mechanisms is investigated at material point level. To account for multiple failure mechanisms, the second-order energy input is linked to the controllability theory and used to define different types of stability indices, each associated with a specific mode of slope failure. It is shown that the theory can be used to assess both shear failure and static liquefaction in saturated and unsaturated soil covers. In particular, it is shown that these instability modes are regulated by the hydro-mechanical characteristics of the soil covers, as well as by their mutual coupling. This finding discloses the importance of the constitutive functions that simulate the interaction between the response of the solid skeleton and the fluid-retention characteristics of the soil. As a consequence, they suggest that even material properties that are not be to directly associated with the shearing resistance (e.g., the potential for wetting compaction) may play a role in the initiation of catastrophic slope failures. According to the proposed interpretation, the process of pore pressure increase can be seen as the trigger of uncontrolled strains, which can anticipate the onset of frictional failure and promote a solid-to-fluid transition.

  11. Is autophagy the key mechanism by which the sphingolipid rheostat controls the cell fate decision?

    PubMed

    Lavieu, Gregory; Scarlatti, Francesca; Sala, Giusy; Levade, Thierry; Ghidoni, Riccardo; Botti, Joëlle; Codogno, Patrice

    2007-01-01

    Sphingolipids are major constituents of biological membrane and some of them behave as second messengers involved in the cell fate decision. Ceramide and sphingosine 1-phosphate (S1P) constitute a rheostat system in which ceramide promotes cell death and S1P increases cell survival. We have shown that both sphingolipids are able to trigger autophagy with opposing outcomes on cell survival. Here we discuss and speculate on the diverging functions of the autophagic pathways induced by ceramide and S1P, respectively.

  12. Determining if an mRNA is a Substrate of Nonsense-Mediated mRNA Decay in Saccharomyces cerevisiae.

    PubMed

    Johansson, Marcus J O

    2017-01-01

    Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic quality control mechanism which triggers decay of mRNAs harboring premature translation termination codons. In this chapter, I describe methods for monitoring the influence of NMD on mRNA abundance and decay rates in Saccharomyces cerevisiae. The descriptions include detailed methods for growing yeast cells, total RNA isolation, and Northern blotting. Although the chapter focuses on NMD, the methods can be easily adapted to assess the effect of other mRNA decay pathways.

  13. Finite-Horizon $H_\\infty $ Consensus for Multiagent Systems With Redundant Channels via An Observer-Type Event-Triggered Scheme.

    PubMed

    Xu, Wenying; Wang, Zidong; Ho, Daniel W C

    2018-05-01

    This paper is concerned with the finite-horizon consensus problem for a class of discrete time-varying multiagent systems with external disturbances and missing measurements. To improve the communication reliability, redundant channels are introduced and the corresponding protocol is constructed for the information transmission over redundant channels. An event-triggered scheme is adopted to determine whether the information of agents should be transmitted to their neighbors. Subsequently, an observer-type event-triggered control protocol is proposed based on the latest received neighbors' information. The purpose of the addressed problem is to design a time-varying controller based on the observed information to achieve the consensus performance in a finite horizon. By utilizing a constrained recursive Riccati difference equation approach, some sufficient conditions are obtained to guarantee the consensus performance, and the controller parameters are also designed. Finally, a numerical example is provided to demonstrate the desired reliability of redundant channels and the effectiveness of the event-triggered control protocol.

  14. Genotype-Dependent Interaction of Lentil Lines with Ascochyta lentis

    PubMed Central

    Sari, Ehsan; Bhadauria, Vijai; Vandenberg, Albert; Banniza, Sabine

    2017-01-01

    Ascochyta blight of lentil is a prevalent disease in many lentil producing regions and can cause major yield and grain quality losses. The most environmentally acceptable and economically profitable method of control is to develop varieties with high levels of durable resistance. Genetic studies to date suggest that ascochyta blight resistance genes (R-gene) in lentil lines CDC Robin, ILL 7537, 964a-46, and ILL 1704 are non-allelic. To understand how different R-genes manifest resistance in these genotypes and an accession of Lens ervoides, L-01-827A, with high level of resistance to ascochyta blight, cellular and molecular defense responses were compared after inoculation with the causal pathogen Ascochyta lentis. Pathogenicity testing of the resistant lines to A. lentis inoculation revealed significantly lower disease severity on CDC Robin and ILL 7537 compared to ILL 1704 and 964a-46, and no symptoms of disease were observed on L-01-827A. Histological examinations indicated that cell death triggered by the pathogen might be disrupted as a mechanism of resistance in CDC Robin. In contrast, limiting colonization of epidermal cells by A. lentis is a suggested mechanism of resistance in 964a-46. A time-series comparison of the expressions of hallmark genes in salicylic acid (SA) and jasmonic acid (JA) signal transduction pathways between CDC Robin and 964a-46 was conducted. These partially resistant genotypes differed in the timing and the magnitude of SA and JA signaling pathway activation. The SA signaling pathway was only triggered in 964a-46, whereas the JA pathway was triggered in both partially resistant genotypes CDC Robin and 964a-46. The expression of JA-associated genes was lower in 964a-46 than CDC Robin. These observations corroborate the existence of diverse ascochyta blight resistance mechanisms in lentil genotypes carrying different R-genes. PMID:28539932

  15. Microbubble-mediated ultrasound therapy: a review of its potential in cancer treatment

    PubMed Central

    Ibsen, Stuart; Schutt, Carolyn E; Esener, Sadik

    2013-01-01

    The inherently toxic nature of chemotherapy drugs is essential for them to kill cancer cells but is also the source of the detrimental side effects experienced by patients. One strategy to reduce these side effects is to limit the healthy tissue exposure by encapsulating the drugs in a vehicle that demonstrates a very low leak rate in circulation while simultaneously having the potential for rapid release once inside the tumor. Designing a vehicle with these two opposing properties is the major challenge in the field of drug delivery. A triggering event is required to change the vehicle from its stable circulating state to its unstable release state. A unique mechanical actuation type trigger is possible by harnessing the size changes that occur when microbubbles interact with ultrasound. These mechanical actuations can burst liposomes and cell membranes alike allowing for rapid drug release and facilitating delivery into nearby cells. The tight focusing ability of the ultrasound to just a few cubic millimeters allows for precise control over the tissue location where the microbubbles destabilize the vehicles. This allows the ultrasound to highlight the tumor tissue and cause rapid drug release from any carrier present. Different vehicle designs have been demonstrated from carrying drug on just the surface of the microbubble itself to encapsulating the microbubble along with the drug within a liposome. In the future, nanoparticles may extend the circulation half-life of these ultrasound triggerable drug-delivery vehicles by acting as nucleation sites of ultrasound-induced mechanical actuation. In addition to the drug delivery capability, the microbubble size changes can also be used to create imaging contrast agents that could allow the internal chemical environment of a tumor to be studied to help improve the diagnosis and detection of cancer. The ability to attain truly tumor-specific release from circulating drug-delivery vehicles is an exciting future prospect to reduce chemotherapy side effects while increasing drug effectiveness. PMID:23667309

  16. Modeling the effects of hydraulic stimulation on geothermal reservoirs

    NASA Astrophysics Data System (ADS)

    De Simone, Silvia; Vilarrasa, Victor; Carrera, Jesús; Alcolea, Andrés; Meier, Peter

    2013-04-01

    Geothermal energy represents a huge power source that can provide clean energy in potentially unlimited supply. When designing geothermal energy production from deep hot rocks, permeability is considered to control the economic efficiency of the heat extraction operations. In fact, a high permeability heat exchanger is required to achieve a cost-competitive power generation. The typical procedure entails intercepting naturally fractured rocks and enhancing their permeability by means of stimulation. Hydraulic stimulation is the most widely used method. It involves the massive injection of a large volume of water at high flow rates to increase the downhole pore pressure. This overpressure reduces the effective stresses, which tends to induce shearing along the fracture planes. In this way permeability is enhanced due to dilatancy, especially in the direction perpendicular to shear. These processes usually trigger microseismic events, which are sometimes of sufficient magnitude to be felt by the local population. This causes a negative impact on the local population and may compromise the continuation of the project. Hence, understanding the mechanisms triggering these induced micro-earthquakes is important to properly design and manage geothermal stimulation and operations so as to prevent them. We analyzed the thermo-hydro-mechanical response of a fractured deep rock mass subjected to hydraulic stimulation. Considering that seismicity is triggered when failure condition are reached, we studied the variation of the stress regime due to the hydraulic and thermal perturbations during fluid injection. Starting with a simplified model with constant permeability fault zones, more sophisticated schemes are considered to simulate the behavior of the discontinuity zones, including permeability variation associated to temperature, pressure and stress regime changes. Numerical simulations are performed using the finite element numerical code CODE_BRIGHT, which allows to solve fully coupled thermo-hydro-mechanical problems. Results allowed to estimate the impact of the hydraulic stimulation on the overall behavior.

  17. TRIGGER MECHANISM OF SOLAR SUBFLARES IN A BRAIDED CORONAL MAGNETIC STRUCTURE

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

    Tiwari, Sanjiv K.; Alexander, Caroline E.; Winebarger, Amy R.

    Fine-scale braiding of coronal magnetic loops by continuous footpoint motions may power coronal heating via nanoflares, which are spontaneous fine-scale bursts of internal reconnection. An initial nanoflare may trigger an avalanche of reconnection of the braids, making a microflare or larger subflare. In contrast to this internal triggering of subflares, we observe external triggering of subflares in a braided coronal magnetic field observed by the High-resolution Coronal Imager (Hi-C). We track the development of these subflares using 12 s cadence images acquired by SDO/AIA in 1600, 193, 94 Å, and registered magnetograms of SDO/HMI, over four hours centered on the Hi-Cmore » observing time. These data show numerous recurring small-scale brightenings in transition-region emission happening on polarity inversion lines where flux cancellation is occurring. We present in detail an example of an apparent burst of reconnection of two loops in the transition region under the braided coronal field which is appropriate for releasing a short reconnected loop downward and a longer reconnected loop upward. The short loop presumably submerges into the photosphere, participating in observed flux cancellation. A subflare in the overlying braided magnetic field is apparently triggered by the disturbance of the braided field by the reconnection-released upward loop. At least 10 subflares observed in this braided structure appear to be triggered this way. How common this external trigger mechanism for coronal subflares is in other active regions, and how important it is for coronal heating in general, remain to be seen.« less

  18. A Ca2+ channel differentially regulates Clathrin-mediated and activity-dependent bulk endocytosis.

    PubMed

    Yao, Chi-Kuang; Liu, Yu-Tzu; Lee, I-Chi; Wang, You-Tung; Wu, Ping-Yen

    2017-04-01

    Clathrin-mediated endocytosis (CME) and activity-dependent bulk endocytosis (ADBE) are two predominant forms of synaptic vesicle (SV) endocytosis, elicited by moderate and strong stimuli, respectively. They are tightly coupled with exocytosis for sustained neurotransmission. However, the underlying mechanisms are ill defined. We previously reported that the Flower (Fwe) Ca2+ channel present in SVs is incorporated into the periactive zone upon SV fusion, where it triggers CME, thus coupling exocytosis to CME. Here, we show that Fwe also promotes ADBE. Intriguingly, the effects of Fwe on CME and ADBE depend on the strength of the stimulus. Upon mild stimulation, Fwe controls CME independently of Ca2+ channeling. However, upon strong stimulation, Fwe triggers a Ca2+ influx that initiates ADBE. Moreover, knockout of rodent fwe in cultured rat hippocampal neurons impairs but does not completely abolish CME, similar to the loss of Drosophila fwe at the neuromuscular junction, suggesting that Fwe plays a regulatory role in regulating CME across species. In addition, the function of Fwe in ADBE is conserved at mammalian central synapses. Hence, Fwe exerts different effects in response to different stimulus strengths to control two major modes of endocytosis.

  19. Microprocessor-controlled, wide-range streak camera

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

    Amy E. Lewis, Craig Hollabaugh

    Bechtel Nevada/NSTec recently announced deployment of their fifth generation streak camera. This camera incorporates many advanced features beyond those currently available for streak cameras. The arc-resistant driver includes a trigger lockout mechanism, actively monitors input trigger levels, and incorporates a high-voltage fault interrupter for user safety and tube protection. The camera is completely modular and may deflect over a variable full-sweep time of 15 nanoseconds to 500 microseconds. The camera design is compatible with both large- and small-format commercial tubes from several vendors. The embedded microprocessor offers Ethernet connectivity, and XML [extensible markup language]-based configuration management with non-volatile parameter storagemore » using flash-based storage media. The camera’s user interface is platform-independent (Microsoft Windows, Unix, Linux, Macintosh OSX) and is accessible using an AJAX [asynchronous Javascript and XML]-equipped modem browser, such as Internet Explorer 6, Firefox, or Safari. User interface operation requires no installation of client software or browser plug-in technology. Automation software can also access the camera configuration and control using HTTP [hypertext transfer protocol]. The software architecture supports multiple-simultaneous clients, multiple cameras, and multiple module access with a standard browser. The entire user interface can be customized.« less

  20. A Ca2+ channel differentially regulates Clathrin-mediated and activity-dependent bulk endocytosis

    PubMed Central

    Liu, Yu-Tzu; Lee, I-Chi; Wang, You-Tung; Wu, Ping-Yen

    2017-01-01

    Clathrin-mediated endocytosis (CME) and activity-dependent bulk endocytosis (ADBE) are two predominant forms of synaptic vesicle (SV) endocytosis, elicited by moderate and strong stimuli, respectively. They are tightly coupled with exocytosis for sustained neurotransmission. However, the underlying mechanisms are ill defined. We previously reported that the Flower (Fwe) Ca2+ channel present in SVs is incorporated into the periactive zone upon SV fusion, where it triggers CME, thus coupling exocytosis to CME. Here, we show that Fwe also promotes ADBE. Intriguingly, the effects of Fwe on CME and ADBE depend on the strength of the stimulus. Upon mild stimulation, Fwe controls CME independently of Ca2+ channeling. However, upon strong stimulation, Fwe triggers a Ca2+ influx that initiates ADBE. Moreover, knockout of rodent fwe in cultured rat hippocampal neurons impairs but does not completely abolish CME, similar to the loss of Drosophila fwe at the neuromuscular junction, suggesting that Fwe plays a regulatory role in regulating CME across species. In addition, the function of Fwe in ADBE is conserved at mammalian central synapses. Hence, Fwe exerts different effects in response to different stimulus strengths to control two major modes of endocytosis. PMID:28414717

  1. Microprocessor-controlled wide-range streak camera

    NASA Astrophysics Data System (ADS)

    Lewis, Amy E.; Hollabaugh, Craig

    2006-08-01

    Bechtel Nevada/NSTec recently announced deployment of their fifth generation streak camera. This camera incorporates many advanced features beyond those currently available for streak cameras. The arc-resistant driver includes a trigger lockout mechanism, actively monitors input trigger levels, and incorporates a high-voltage fault interrupter for user safety and tube protection. The camera is completely modular and may deflect over a variable full-sweep time of 15 nanoseconds to 500 microseconds. The camera design is compatible with both large- and small-format commercial tubes from several vendors. The embedded microprocessor offers Ethernet connectivity, and XML [extensible markup language]-based configuration management with non-volatile parameter storage using flash-based storage media. The camera's user interface is platform-independent (Microsoft Windows, Unix, Linux, Macintosh OSX) and is accessible using an AJAX [asynchronous Javascript and XML]-equipped modem browser, such as Internet Explorer 6, Firefox, or Safari. User interface operation requires no installation of client software or browser plug-in technology. Automation software can also access the camera configuration and control using HTTP [hypertext transfer protocol]. The software architecture supports multiple-simultaneous clients, multiple cameras, and multiple module access with a standard browser. The entire user interface can be customized.

  2. Migraine, arousal and sleep deprivation: comment on: “sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study”

    PubMed Central

    2013-01-01

    We discuss the hypothesis proposed by Engstrom and coworkers that Migraineurs have a relative sleep deprivation, which lowers the pain threshold and predispose to attacks. Previous data indicate that Migraineurs have a reduction of Cyclic Alternating Pattern (CAP), an essential mechanism of NREM sleep regulation which allows to dump the effect of incoming disruptive stimuli, and to protect sleep. The modifications of CAP observed in Migraineurs are similar to those observed in patients with impaired arousal (narcolepsy) and after sleep deprivation. The impairment of this mechanism makes Migraineurs more vulnerable to stimuli triggering attacks during sleep, and represents part of a more general vulnerability to incoming stimuli. PMID:23758606

  3. Mitochondria control acute and chronic responses to hypoxia.

    PubMed

    McElroy, G S; Chandel, N S

    2017-07-15

    There are numerous mechanisms by which mammals respond to hypoxia. These include acute changes in pulmonary arterial tone due to smooth muscle cell contraction, acute increases in respiration triggered by the carotid body chemosensory cells, and chronic changes such as induction of red blood cell proliferation and angiogenesis by hypoxia inducible factor targets erythropoietin and vascular endothelial growth factor, respectively. Mitochondria account for the majority of oxygen consumption in the cell and have recently been appreciated to serve as signaling organelles required for the initiation or propagation of numerous homeostatic mechanisms. Mitochondria can influence cell signaling by production of reactive oxygen species and metabolites. Here we review recent evidence that mitochondrial signals can imitate acute and chronic hypoxia responses. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. ER-stress and apoptosis: molecular mechanisms and potential relevance in infection.

    PubMed

    Häcker, Georg

    2014-10-01

    During ER-stress, one of the responses a cell can choose is apoptosis. Apoptosis generally is a cell's preferred response when other control mechanisms are overwhelmed. We now have a reasonably clear molecular picture what is happening once the apoptotic apparatus has been started. Unclear however are the majority of the upstream pathways that connect other signalling to apoptosis. During ER-stress, confirmed apoptosis-regulating targets are pro- and anti-apoptotic proteins of the Bcl-2-family, whose concerted action induces apoptosis. I will here discuss how mitochondrial apoptosis is triggered, how this is linked to the ER-stress response and in what way this may be relevant during microbial infections. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  5. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension

    PubMed Central

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A.; Castillo, Andrés E.; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E.; Kalergis, Alexis M.

    2016-01-01

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage. PMID:27347925

  6. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension.

    PubMed

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A; Castillo, Andrés E; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E; Kalergis, Alexis M

    2016-06-23

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage.

  7. A checkpoint control orchestrates the replication of the two chromosomes of Vibrio cholerae

    PubMed Central

    Val, Marie-Eve; Marbouty, Martial; de Lemos Martins, Francisco; Kennedy, Sean P.; Kemble, Harry; Bland, Michael J.; Possoz, Christophe; Koszul, Romain; Skovgaard, Ole; Mazel, Didier

    2016-01-01

    Bacteria with multiple chromosomes represent up to 10% of all bacterial species. Unlike eukaryotes, these bacteria use chromosome-specific initiators for their replication. In all cases investigated, the machineries for secondary chromosome replication initiation are of plasmid origin. One of the important differences between plasmids and chromosomes is that the latter replicate during a defined period of the cell cycle, ensuring a single round of replication per cell. Vibrio cholerae carries two circular chromosomes, Chr1 and Chr2, which are replicated in a well-orchestrated manner with the cell cycle and coordinated in such a way that replication termination occurs at the same time. However, the mechanism coordinating this synchrony remains speculative. We investigated this mechanism and revealed that initiation of Chr2 replication is triggered by the replication of a 150-bp locus positioned on Chr1, called crtS. This crtS replication–mediated Chr2 replication initiation mechanism explains how the two chromosomes communicate to coordinate their replication. Our study reveals a new checkpoint control mechanism in bacteria, and highlights possible functional interactions mediated by contacts between two chromosomes, an unprecedented observation in bacteria. PMID:27152358

  8. Linear servomotor probe drive system with real-time self-adaptive position control for the Alcator C-Mod tokamak

    NASA Astrophysics Data System (ADS)

    Brunner, D.; Kuang, A. Q.; LaBombard, B.; Burke, W.

    2017-07-01

    A new servomotor drive system has been developed for the horizontal reciprocating probe on the Alcator C-Mod tokamak. Real-time measurements of plasma temperature and density—through use of a mirror Langmuir probe bias system—combined with a commercial linear servomotor and controller enable self-adaptive position control. Probe surface temperature and its rate of change are computed in real time and used to control probe insertion depth. It is found that a universal trigger threshold can be defined in terms of these two parameters; if the probe is triggered to retract when crossing the trigger threshold, it will reach the same ultimate surface temperature, independent of velocity, acceleration, or scrape-off layer heat flux scale length. In addition to controlling the probe motion, the controller is used to monitor and control all aspects of the integrated probe drive system.

  9. The role of electrostatics in TrxR electron transfer mechanism: A computational approach.

    PubMed

    Teixeira, Vitor H; Capacho, Ana Sofia C; Machuqueiro, Miguel

    2016-12-01

    Thioredoxin reductase (TrxR) is an important enzyme in the control of the intracellular reduced redox environment. It transfers electrons from NADPH to several molecules, including its natural partner, thioredoxin. Although there is a generally accepted model describing how the electrons are transferred along TrxR, which involves a flexible arm working as a "shuttle," the molecular details of such mechanism are not completely understood. In this work, we use molecular dynamics simulations with Poisson-Boltzmann/Monte Carlo pKa calculations to investigate the role of electrostatics in the electron transfer mechanism. We observed that the combination of redox/protonation states of the N-terminal (FAD and Cys59/64) and C-terminal (Cys497/Selenocysteine498) redox centers defines the preferred relative positions and allows for the flexible arm to work as the desired "shuttle." Changing the redox/ionization states of those key players, leads to electrostatic triggers pushing the arm into the pocket when oxidized, and pulling it out, once it has been reduced. The calculated pKa values for Cys497 and Selenocysteine498 are 9.7 and 5.8, respectively, confirming that the selenocysteine is indeed deprotonated at physiological pH. This can be an important advantage in terms of reactivity (thiolate/selenolate are more nucleophilic than thiol/selenol) and ability to work as an electrostatic trigger (the "shuttle" mechanism) and may be the reason why TrxR uses selenium instead of sulfur. Proteins 2016; 84:1836-1843. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Patient-specific computer-based decision support in primary healthcare--a randomized trial.

    PubMed

    Kortteisto, Tiina; Raitanen, Jani; Komulainen, Jorma; Kunnamo, Ilkka; Mäkelä, Marjukka; Rissanen, Pekka; Kaila, Minna

    2014-01-20

    Computer-based decision support systems are a promising method for incorporating research evidence into clinical practice. However, evidence is still scant on how such information technology solutions work in primary healthcare when support is provided across many health problems. In Finland, we designed a trial where a set of evidence-based, patient-specific reminders was introduced into the local Electronic Patient Record (EPR) system. The aim was to measure the effects of such reminders on patient care. The hypothesis was that the total number of triggered reminders would decrease in the intervention group compared with the control group, indicating an improvement in patient care. From July 2009 to October 2010 all the patients of one health center were randomized to an intervention or a control group. The intervention consisted of patient-specific reminders concerning 59 different health conditions triggered when the healthcare professional (HCP) opened and used the EPR. In the intervention group, the triggered reminders were shown to the HCP; in the control group, the triggered reminders were not shown. The primary outcome measure was the change in the number of reminders triggered over 12 months. We developed a unique data gathering method, the Repeated Study Virtual Health Check (RSVHC), and used Generalized Estimation Equations (GEE) for analysing the incidence rate ratio, which is a measure of the relative difference in percentage change in the numbers of reminders triggered in the intervention group and the control group. In total, 13,588 participants were randomized and included. Contrary to our expectation, the total number of reminders triggered increased in both the intervention and the control groups. The primary outcome measure did not show a significant difference between the groups. However, with the inclusion of patients followed up over only six months, the total number of reminders increased significantly less in the intervention group than in the control group when the confounding factors (age, gender, number of diagnoses and medications) were controlled for. Computerized, tailored reminders in primary care did not decrease during the 12 months of follow-up time after the introduction of a patient-specific decision support system. ClinicalTrial.gov NCT00915304.

  11. The ITER disruption mitigation trigger: developing its preliminary design

    NASA Astrophysics Data System (ADS)

    Pautasso, G.; de Vries, P. C.; Humphreys, D.; Lehnen, M.; Rapson, C.; Raupp, G.; Snipes, J. A.; Treutterer, W.; Vergara-Fernandez, A.; Zabeo, L.

    2018-03-01

    A concept for the generation of the trigger for the ITER disruption mitigation system is described in this paper. The issuing of the trigger will be the result of a complex decision process, taken by the plasma control system, or by the central interlock system, determining that the plasma is unavoidably going to disrupt—or has disrupted—and that a fast mitigated shut-down is required. Given the redundancy of the mitigation system, the plasma control system must also formulate an injection scheme and specify when and how the injectors of the mitigation system should be activated. The parameters and the conceptual algorithms required for the configuration and generation of the trigger are discussed.

  12. Triggering active galactic nuclei in galaxy clusters

    NASA Astrophysics Data System (ADS)

    Marshall, Madeline A.; Shabala, Stanislav S.; Krause, Martin G. H.; Pimbblet, Kevin A.; Croton, Darren J.; Owers, Matt S.

    2018-03-01

    We model the triggering of active galactic nuclei (AGN) in galaxy clusters using the semi-analytic galaxy formation model SAGE. We prescribe triggering methods based on the ram pressure galaxies experience as they move throughout the intracluster medium, which is hypothesized to trigger star formation and AGN activity. The clustercentric radius and velocity distribution of the simulated active galaxies produced by these models are compared with those of AGN and galaxies with intense star formation from a sample of low-redshift relaxed clusters from the Sloan Digital Sky Survey. The ram pressure triggering model that best explains the clustercentric radius and velocity distribution of these observed galaxies has AGN and star formation triggered if 2.5 × 10-14 Pa < Pram < 2.5 × 10-13 Pa and Pram > 2Pinternal; this is consistent with expectations from hydrodynamical simulations of ram-pressure-induced star formation. Our results show that ram pressure is likely to be an important mechanism for triggering star formation and AGN activity in clusters.

  13. Design and investigation of a multichannel laser-triggered vacuum switch

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

    Fan, Wenfang, E-mail: fwf1990@126.com; He, Zhenghao; Mao, Xiaopo

    2016-03-15

    A laser-triggered vacuum switch (LTVS) is an advanced closing switch with nanosecond delay and jitter. In order to enhance hold-off voltage and extend the service lifetime of an LTVS, we designed a multichannel laser-triggered vacuum switch (MLTVS) utilizing a cone-shaped target electrode placed on the cathode platform. The fabrication and testing of the MLTVS is described in this paper. Experimental results show that the working voltage of the MLTVS with a gap distance of 12 mm is from 30 V to 20 kV. The threshold energy for triggering the switch is 0.4 mJ corresponding to a peak power density ofmore » 27.9 MW/cm{sup 2}. The triggering lifetime of a spot can reach up to 18 000 shots. In addition, the relationship between triggering lifetime and target materials is analyzed using a field emission scanning electron microscope. A hypothesis of the vacuum gap’s triggering mechanism is discussed based on the measured results.« less

  14. Physiological regulation through learnt control of appetites by contingencies among signals from external and internal environments.

    PubMed

    Booth, David A

    2008-11-01

    As reviewed by [Cooper, S. J. (2008). From Claude Bernard to Walter Cannon: emergence of the concept of homeostasis. Appetite 51, 419-27.] Claude Bernard's idea of stabilisation of bodily states, as realised in Walter B. Cannon's conception of homeostasis, took mathematical form during the 1940s in the principle that externally originating disturbance of a physiological parameter can feed an informative signal around the brain to trigger counteractive processes--a corrective mechanism known as negative feedback, in practice reliant on feedforward. Three decades later, enough was known of the physiology and psychology of eating and drinking for calculations to show how experimentally demonstrated mechanisms of feedforward that had been learnt from negative feedback combine to regulate exchanges of water and energy between the body and the surroundings. Subsequent systemic physiology, molecular neuroscience and experimental psychology, however, have been traduced by a misconception that learnt controls of intake are 'non-homeostatic', the myth of biological 'set points' and an historic failure to address evidence for the ingestion-adapting information-processing mechanisms on which an operationally integrative theory of eating and drinking relies.

  15. Remotely triggered nonvolcanic tremor in Sumbawa, Indonesia

    NASA Astrophysics Data System (ADS)

    Fuchs, Florian; Lupi, Matteo; Miller, Stephen

    2015-04-01

    Nonvolcanic (or tectonic) tremor is a seismic phenomenom which can provide important information about dynamics of plate boundaries but the underlying mechanisms are not well understood. Tectonic tremor is often associated with slow-slip (termed episodic tremor and slip) and understanding the mechanisms driving tremor presents an important challenge because it is likely a dominant aspect of the evolutionary processes leading to tsunamigenic, megathrust subduction zone earthquakes. Tectonic tremor is observed worldwide, mainly along major subduction zones and plate boundaries such as in Alaska/Aleutians, Cascadia, the San Andreas Fault, Japan or Taiwan. We present, for the first time, evidence for triggered tremor beneath the island of Sumbawa, Indonesia. The island of Sumbawa, Indonesia, is part of the Lesser Sunda Group about 250 km north of the Australian/Eurasian plate collision at the Java Trench with a convergence rate of approximately 70 mm/yr. We show surface wave triggered tremor beneath Sumbawa in response to three teleseismic earthquakes: the Mw9.0 2011 Tohoku earthquake and two oceanic strike-slip earthquakes (Mw 8.6 and Mw8.2) offshore of Sumatra in 2012. Tremor amplitudes scale with ground motion and peak at 180 nm/s ground velocity on the horizontal components. A comparison of ground motion of the three triggering events and a similar (nontriggering) Mw7.6 2012 Philippines event constrains an apparent triggering threshold of approximately 1 mm/s ground velocity or 8 kPa dynamic stress. Surface wave periods of 45-65 s appear optimal for triggering tremor at Sumbawa which predominantly correlates with Rayleigh waves, even though the 2012 oceanic events have stronger Love wave amplitudes and triggering potential. Rayleigh wave triggering, low-triggering amplitudes, and the tectonic setting all favor a model of tremor generated by localized fluid transport. We could not locate the tremor because of minimal station coverage, but data indicate several potential source volumes including the Flores Thrust, the Java subduction zone, or Tambora volcano.

  16. Method for triggering an action

    DOEpatents

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

    2006-10-17

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

  17. Is There an Association Between Lumbosacral Radiculopathy and Painful Gluteal Trigger Points?: A Cross-sectional Study.

    PubMed

    Adelmanesh, Farhad; Jalali, Ali; Jazayeri Shooshtari, Seyed Mostafa; Raissi, Gholam Reza; Ketabchi, Seyed Mehdi; Shir, Yoram

    2015-10-01

    The objective of this study was to compare the prevalence of gluteal trigger point in patients with lumbosacral radiculopathy with that in healthy volunteers. In a cross-sectional, multistage sampling method, patients with clinical, electromyographic, and magnetic resonance imaging findings consistent with lumbosacral radiculopathy were examined for the presence of gluteal trigger point. Age- and sex-matched clusters of healthy volunteers were selected as the control group. The primary outcome of the study was the presence or absence of gluteal trigger point in the gluteal region of the patients and the control group. Of 441 screened patients, 271 met all the inclusion criteria for lumbosacral radiculopathy and were included in the study. Gluteal trigger point was identified in 207 (76.4%) of the 271 patients with radiculopathy, compared with 3 (1.9%) of 152 healthy volunteers (P < 0.001). The location of gluteal trigger point matched the side of painful radiculopathy in 74.6% of patients with a unilateral radicular pain. There was a significant correlation between the side of the gluteal trigger point and the side of patients' radicular pain (P < 0.001). Although rare in the healthy volunteers, most of the patients with lumbosacral radiculopathy had gluteal trigger point, located at the painful side. Further studies are required to test the hypothesis that specific gluteal trigger point therapy could be beneficial in these patients.

  18. Constraints and triggers: situational mechanics of gender in negotiation.

    PubMed

    Bowles, Hannah Riley; Babcock, Linda; McGinn, Kathleen L

    2005-12-01

    The authors propose 2 categories of situational moderators of gender in negotiation: situational ambiguity and gender triggers. Reducing the degree of situational ambiguity constrains the influence of gender on negotiation. Gender triggers prompt divergent behavioral responses as a function of gender. Field and lab studies (1 and 2) demonstrated that decreased ambiguity in the economic structure of a negotiation (structural ambiguity) reduces gender effects on negotiation performance. Study 3 showed that representation role (negotiating for self or other) functions as a gender trigger by producing a greater effect on female than male negotiation performance. Study 4 showed that decreased structural ambiguity constrains gender effects of representation role, suggesting that situational ambiguity and gender triggers work in interaction to moderate gender effects on negotiation performance. Copyright 2006 APA, all rights reserved.

  19. A high voltage pulse generator based on silicon-controlled rectifier for field-reversed configuration experiment.

    PubMed

    Lin, Munan; Liu, Ming; Zhu, Guanghui; Wang, Yanpeng; Shi, Peiyun; Sun, Xuan

    2017-08-01

    A high voltage pulse generator based on a silicon-controlled rectifier has been designed and implemented for a field reversed configuration experiment. A critical damping circuit is used in the generator to produce the desired pulse waveform. Depending on the load, the rise time of the output trigger signal can be less than 1 μs, and the peak amplitudes of trigger voltage and current are up to 8 kV and 85 A in a single output. The output voltage can be easily adjusted by changing the voltage on a capacitor of the generator. In addition, the generator integrates an electrically floating heater circuit so it is capable of triggering either pseudosparks (TDI-type hydrogen thyratron) or ignitrons. Details of the circuits and their implementation are described in the paper. The trigger generator has successfully controlled the discharging sequence of the pulsed power supply for a field reversed configuration experiment.

  20. A high voltage pulse generator based on silicon-controlled rectifier for field-reversed configuration experiment

    NASA Astrophysics Data System (ADS)

    Lin, Munan; Liu, Ming; Zhu, Guanghui; Wang, Yanpeng; Shi, Peiyun; Sun, Xuan

    2017-08-01

    A high voltage pulse generator based on a silicon-controlled rectifier has been designed and implemented for a field reversed configuration experiment. A critical damping circuit is used in the generator to produce the desired pulse waveform. Depending on the load, the rise time of the output trigger signal can be less than 1 μs, and the peak amplitudes of trigger voltage and current are up to 8 kV and 85 A in a single output. The output voltage can be easily adjusted by changing the voltage on a capacitor of the generator. In addition, the generator integrates an electrically floating heater circuit so it is capable of triggering either pseudosparks (TDI-type hydrogen thyratron) or ignitrons. Details of the circuits and their implementation are described in the paper. The trigger generator has successfully controlled the discharging sequence of the pulsed power supply for a field reversed configuration experiment.

  1. Exponential Synchronization of Networked Chaotic Delayed Neural Network by a Hybrid Event Trigger Scheme.

    PubMed

    Fei, Zhongyang; Guan, Chaoxu; Gao, Huijun; Zhongyang Fei; Chaoxu Guan; Huijun Gao; Fei, Zhongyang; Guan, Chaoxu; Gao, Huijun

    2018-06-01

    This paper is concerned with the exponential synchronization for master-slave chaotic delayed neural network with event trigger control scheme. The model is established on a network control framework, where both external disturbance and network-induced delay are taken into consideration. The desired aim is to synchronize the master and slave systems with limited communication capacity and network bandwidth. In order to save the network resource, we adopt a hybrid event trigger approach, which not only reduces the data package sending out, but also gets rid of the Zeno phenomenon. By using an appropriate Lyapunov functional, a sufficient criterion for the stability is proposed for the error system with extended ( , , )-dissipativity performance index. Moreover, hybrid event trigger scheme and controller are codesigned for network-based delayed neural network to guarantee the exponential synchronization between the master and slave systems. The effectiveness and potential of the proposed results are demonstrated through a numerical example.

  2. Earthquake triggering in southeast Africa following the 2012 Indian Ocean earthquake

    NASA Astrophysics Data System (ADS)

    Neves, Miguel; Custódio, Susana; Peng, Zhigang; Ayorinde, Adebayo

    2018-02-01

    In this paper we present evidence of earthquake dynamic triggering in southeast Africa. We analysed seismic waveforms recorded at 53 broad-band and short-period stations in order to identify possible increases in the rate of microearthquakes and tremor due to the passage of teleseismic waves generated by the Mw8.6 2012 Indian Ocean earthquake. We found evidence of triggered local earthquakes and no evidence of triggered tremor in the region. We assessed the statistical significance of the increase in the number of local earthquakes using β-statistics. Statistically significant dynamic triggering of local earthquakes was observed at 7 out of the 53 analysed stations. Two of these stations are located in the northeast coast of Madagascar and the other five stations are located in the Kaapvaal Craton, southern Africa. We found no evidence of dynamically triggered seismic activity in stations located near the structures of the East African Rift System. Hydrothermal activity exists close to the stations that recorded dynamic triggering, however, it also exists near the East African Rift System structures where no triggering was observed. Our results suggest that factors other than solely tectonic regime and geothermalism are needed to explain the mechanisms that underlie earthquake triggering.

  3. [A novel serial port auto trigger system for MOSFET dose acquisition].

    PubMed

    Luo, Guangwen; Qi, Zhenyu

    2013-01-01

    To synchronize the radiation of microSelectron-HDR (Nucletron afterloading machine) and measurement of MOSFET dose system, a trigger system based on interface circuit was designed and corresponding monitor and trigger program were developed on Qt platform. This interface and control system was tested and showed stable operate and reliable work. This adopted serial port detect technique may expand to trigger application of other medical devices.

  4. Reflex seizures in Rett syndrome.

    PubMed

    Roche Martínez, Ana; Alonso Colmenero, M Itziar; Gomes Pereira, Andreia; Sanmartí Vilaplana, Francesc X; Armstrong Morón, Judith; Pineda Marfa, Mercé

    2011-12-01

    Reflex seizures are a rare phenomenon among epileptic patients, in which an epileptic discharge is triggered by various kinds of stimuli (visual, auditory, tactile or gustatory). Epilepsy is common in Rett syndrome patients (up to 70%), but to the authors' knowledge, no pressure or eating-triggered seizures have yet been reported in Rett children. We describe three epileptic Rett patients with reflex seizures, triggered by food intake or proprioception. One patient with congenital Rett Sd. developed infantile epileptic spasms at around seven months and two patients with classic Rett Sd. presented with generalised tonic-clonic seizures at around five years. Reflex seizures appeared when the patients were teenagers. The congenital-Rett patient presented eating-triggered seizures at the beginning of almost every meal, demonstrated by EEG recording. Both classic Rett patients showed self-provoked pressure -triggered attacks, influenced by stress or excitement. Non-triggered seizures were controlled with carbamazepine or valproate, but reflex seizures did not respond to antiepileptic drugs. Risperidone partially improved self-provoked seizures. When reflex seizures are suspected, reproducing the trigger during EEG recording is fundamental; however, self-provoked seizures depend largely on the patient's will. Optimal therapy (though not always possible) consists of avoiding the trigger. Stress modifiers such as risperidone may help control self-provoked seizures.

  5. Lightning initiation mechanism based on the development of relativistic runaway electron avalanches triggered by background cosmic radiation: Numerical simulation

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

    Babich, L. P., E-mail: babich@elph.vniief.ru; Bochkov, E. I.; Kutsyk, I. M.

    2011-05-15

    The mechanism of lightning initiation due to electric field enhancement by the polarization of a conducting channel produced by relativistic runaway electron avalanches triggered by background cosmic radiation has been simulated numerically. It is shown that the fields at which the start of a lightning leader is possible even in the absence of precipitations are locally realized for realistic thundercloud configurations and charges. The computational results agree with the in-situ observations of penetrating radiation enhancement in thunderclouds.

  6. Free radical-triggered hepatic injury of experimental obstructive jaundice of rats involves overproduction of proinflammatory cytokines and enhanced activation of nuclear factor kappaB.

    PubMed

    Liu, T Z; Lee, K T; Chern, C L; Cheng, J T; Stern, A; Tsai, L Y

    2001-10-01

    Excessive production of hydroxyl radicals in blood and liver has previously been demonstrated by us in rats with obstructive jaundice induced by common bile duct ligation (CBDL). In this study, we demonstrate overproduction of superoxide radicals in circulating blood of CBDL rats by the lucigenin-amplified chemiluminescence technique. To pinpoint the molecular agents that mediate these processes, we measured circulating proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta ( IL-1beta), and interleukin-6 (IL-6) in controls and CBDL rats. Concentrations of these cytokines in blood of CBDL rats were markedly elevated when compared to the controls (TNF-alpha: 36.7 +/- 5.0 vs 13.8 +/- 0.5 pg/mL; IL-6: 2,814 +/- 1,740 vs 0 pg/mL; IL-1beta: 11.9 +/- 2.6 vs 0 pg/mL). The overproduction of free radicals triggered by elevated cytokines in CBDL rats was correlated with the activation of NF-kappaB in hepatic tissue. Using the TdT-mediated dUTP nick-end label staining technique, we showed that hepatic tissue sections from CBDL rats had an increase in the apoptotic index (AI). Based on these findings, we propose that the severe hepatic injury in CBDL rats is mediated by a cycle that involves the activation of NF-kappaB by combined action of proinflammatory cytokines and reactive oxygen species (ROS). NF-KB, in turn, initiates the transcription of cytokine genes (eg, IL-6, IL-8, TNF-alpha), which triggers hepatic injury, at least in part, by a free radical-mediated apoptotic mechanism. Elevated ROS may be as a positive-feedback signal that triggers NF-KB reactivation; the severe hepatic injury of CBDL rats may result from perpetuation of this vicious cycle.

  7. A model of cardiac ryanodine receptor gating predicts experimental Ca2+-dynamics and Ca2+-triggered arrhythmia in the long QT syndrome

    NASA Astrophysics Data System (ADS)

    Wilson, Dan; Ermentrout, Bard; Němec, Jan; Salama, Guy

    2017-09-01

    Abnormal Ca2+ handling is well-established as the trigger of cardiac arrhythmia in catecholaminergic polymorphic ventricular tachycardia and digoxin toxicity, but its role remains controversial in Torsade de Pointes (TdP), the arrhythmia associated with the long QT syndrome (LQTS). Recent experimental results show that early afterdepolarizations (EADs) that initiate TdP are caused by spontaneous (non-voltage-triggered) Ca2+ release from Ca2+-overloaded sarcoplasmic reticulum (SR) rather than the activation of the L-type Ca2+-channel window current. In bradycardia and long QT type 2 (LQT2), a second, non-voltage triggered cytosolic Ca2+ elevation increases gradually in amplitude, occurs before overt voltage instability, and then precedes the rise of EADs. Here, we used a modified Shannon-Puglisi-Bers model of rabbit ventricular myocytes to reproduce experimental Ca2+ dynamics in bradycardia and LQT2. Abnormal systolic Ca2+-oscillations and EADs caused by SR Ca2+-release are reproduced in a modified 0-dimensional model, where 3 gates in series control the ryanodine receptor (RyR2) conductance. Two gates control RyR2 activation and inactivation and sense cytosolic Ca2+ while a third gate senses luminal junctional SR Ca2+. The model predicts EADs in bradycardia and low extracellular [K+] and cessation of SR Ca2+-release terminate salvos of EADs. Ca2+-waves, systolic cell-synchronous Ca2+-release, and multifocal diastolic Ca2+ release seen in subcellular Ca2+-mapping experiments are observed in the 2-dimensional version of the model. These results support the role of SR Ca2+-overload, abnormal SR Ca2+-release, and the subsequent activation of the electrogenic Na+/Ca2+-exchanger as the mechanism of TdP. The model offers new insights into the genesis of cardiac arrhythmia and new therapeutic strategies.

  8. Magnetohydrodynamic Simulations for Studying Solar Flare Trigger Mechanism

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

    Muhamad, J.; Kusano, K.; Inoue, S.

    In order to understand the flare trigger mechanism, we conduct three-dimensional magnetohydrodynamic simulations using a coronal magnetic field model derived from data observed by the Hinode satellite. Several types of magnetic bipoles are imposed into the photospheric boundary of the Nonlinear Force-free Field model of Active Region (AR) NOAA 10930 on 2006 December 13, to investigate what kind of magnetic disturbance may trigger the flare. As a result, we confirm that certain small bipole fields, which emerge into the highly sheared global magnetic field of an AR, can effectively trigger a flare. These bipole fields can be classified into twomore » groups based on their orientation relative to the polarity inversion line: the so-called opposite polarity, and reversed shear structures, as suggested by Kusano et al. We also investigate the structure of the footpoints of reconnected field lines. By comparing the distribution of reconstructed field lines and observed flare ribbons, the trigger structure of the flare can be inferred. Our simulation suggests that the data-constrained simulation, taking into account both the large-scale magnetic structure and small-scale magnetic disturbance (such as emerging fluxes), is a good way to discover a flare-producing AR, which can be applied to space weather prediction.« less

  9. Mechanically triggered heterolytic unzipping of a low-ceiling-temperature polymer

    NASA Astrophysics Data System (ADS)

    Diesendruck, Charles E.; Peterson, Gregory I.; Kulik, Heather J.; Kaitz, Joshua A.; Mar, Brendan D.; May, Preston A.; White, Scott R.; Martínez, Todd J.; Boydston, Andrew J.; Moore, Jeffrey S.

    2014-07-01

    Biological systems rely on recyclable materials resources such as amino acids, carbohydrates and nucleic acids. When biomaterials are damaged as a result of aging or stress, tissues undergo repair by a depolymerization-repolymerization sequence of remodelling. Integration of this concept into synthetic materials systems may lead to devices with extended lifetimes. Here, we show that a metastable polymer, end-capped poly(o-phthalaldehyde), undergoes mechanically initiated depolymerization to revert the material to monomers. Trapping experiments and steered molecular dynamics simulations are consistent with a heterolytic scission mechanism. The obtained monomer was repolymerized by a chemical initiator, effectively completing a depolymerization-repolymerization cycle. By emulating remodelling of biomaterials, this model system suggests the possibility of smart materials where aging or mechanical damage triggers depolymerization, and orthogonal conditions regenerate the polymer when and where necessary.

  10. Investigation of index finger triggering force using a cadaver experiment: Effects of trigger grip span, contact location, and internal tendon force.

    PubMed

    Chang, Joonho; Freivalds, Andris; Sharkey, Neil A; Kong, Yong-Ku; Mike Kim, H; Sung, Kiseok; Kim, Dae-Min; Jung, Kihyo

    2017-11-01

    A cadaver study was conducted to investigate the effects of triggering conditions (trigger grip span, contact location, and internal tendon force) on index finger triggering force and the force efficiency of involved tendons. Eight right human cadaveric hands were employed, and a motion simulator was built to secure and control the specimens. Index finger triggering forces were investigated as a function of different internal tendon forces (flexor digitorum profundus + flexor digitorum superficialis = 40, 70, and 100 N), trigger grip spans (40, 50, and 60 mm), and contact locations between the index finger and a trigger. Triggering forces significantly increased when internal tendon forces increased from 40 to 100 N. Also, trigger grip spans and contact locations had significant effects on triggering forces; maximum triggering forces were found at a 50 mm span and the most proximal contact location. The results revealed that only 10-30% of internal tendon forces were converted to their external triggering forces. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Electronics design of the RPC system for the OPERA muon spectrometer

    NASA Astrophysics Data System (ADS)

    Acquafredda, R.; Ambrosio, M.; Balsamo, E.; Barichello, G.; Bergnoli, A.; Consiglio, L.; Corradi, G.; dal Corso, F.; Felici, G.; Manea, C.; Masone, V.; Parascandolo, P.; Sorrentino, G.

    2004-09-01

    The present document describes the front-end electronics of the RPC system that instruments the magnet muon spectrometer of the OPERA experiment. The main task of the OPERA spectrometer is to provide particle tracking information for muon identification and simplify the matching between the Precision Trackers. As no trigger has been foreseen for the experiment, the spectrometer electronics must be self-triggered with single-plane readout capability. Moreover, precision time information must be added within each event frame for off-line reconstruction. The read-out electronics is made of three different stages: the Front-End Boards (FEBs) system, the Controller Boards (CBs) system and the Trigger Boards (TBs) system. The FEB system provides discrimination of the strip incoming signals; a FAST-OR output of the input signals is also available for trigger plane signal generation. FEB signals are acquired by the CB system that provides the zero suppression and manages the communication to the DAQ and Slow Control. A Trigger Board allows to operate in both self-trigger mode (the FEB's FAST-OR signal starts the plane acquisition) or in external-trigger mode (different conditions can be set on the FAST-OR signals generated from different planes).

  12. Study of Tectonic Tremor in Depth: Triggering Stress Observation and Model of the Triggering Mechanism

    NASA Astrophysics Data System (ADS)

    Wang, Tien-Huei

    Non-volcanic tremor (NVT) has been discovered in recent years due to advances in seismic instruments and increased density of seismic networks. The NVT is a special kind of seismic signal indicative of the physical conditions and the failure mechanism on the source on the fault where NVT occurs. The detection methods used and the sensitivity of them relies on the density, distance and instrumentation of the station network available. How accurately the tremor is identified in different regions varies greatly among different studies. Therefore, there has not been study that rigorously documents tectonic tremors in different regions under limited methods and data. Meanwhile, many incidences of NVTs are observed during or after small but significant strain change induced by teleseismic, regional or local earthquake. The understanding of the triggering mechanisms critical for tremor remains unclear. In addition, characteristics of the triggering of NVT in different regions are rarely compared because of the short time frame after the discovery of the triggered NVTs. We first explore tectonic tremor based on observations to learn about its triggering, frequency of occurrence, location and spectral characteristics. Then, we numerically model the triggering of instability on the estimated tremor-source, under assumptions fine-tuned according to previous studies (Thomas et al., 2009; Miyazawa et al., 2005; Hill, 2008; Ito, 2009; Rubinstein et al., 2007; Peng and Chao, 2008). The onset of the slip reveals that how and when the external loading triggers tremor. It also holds the information to the background stress conditions under which tremor source starts with. We observe and detect tremor in two regions: Anza and Cholame, along San Jacinto Fault (SJF) and San Andreas Fault (SAF) respectively. These two sections of the faults, relative to general fault zone on which general earthquakes occur, are considered transition zones where slip of slow rates occurs. Slip events including NVT occur on these sections have slower slip rates than that of the general earthquakes (Rubin, 2008; Ide, 2008). In Azna region, we use envelope and waveform cross-correlation to detect tremor. We investigate the stress required to trigger tremor and tremor spectrum using continuous broadband seismograms from 11 stations located near Anza, California. We examine 44 Mw≥7.4 teleseismic events between 2001 and 2011, in addition to one regional earthquake of smaller-magnitude, the 2009 Mw 6.5 Gulf of California earthquake, because it induced extremely high strain at Anza. The result suggests that not only the amplitude of the induced strain, but also the period of the incoming surface wave, may control triggering of tremor near Anza. In addition, we find that the transient-shear stress (17--35 kPa) required to trigger tremor along the SJF at Anza is distinctly higher than what has been reported for the well-studied SAF (Gulihem et al. 2010). We model slip initiation using the analytical solution of rate-and-state friction. We verify the correctness of this method by comparing the results with that from the dynamic model, implemented using the Multi-Dimensional Spectral Boundary Integral Code (MDSBI) written by Eric M. Dunham from Sanford University. We find that the analytical result is consistent with that of the dynamic model. We set up a patch model with which the source stress and frictional conditions best resemble the current estimates of the tremor source. The frictional regime of this patch is rate-weakening. The initial normal and shear stress, and friction parameters are suggested by previous observations of tectonic tremors both in this and other studies (Brown et al., 2005; Shelly et al., 2006; Miyazawa, 2008; Ben-Zion, 2012). Our dynamic loading first consists of simple harmonic stress change with fixed periods, simplifying the transient stress history to resemble teleseismic earthquakes. We tested the period and amplitude of such periodic loading. We find that the period of the transient shear stress is less important relative to the amplitude. The triggering depends mainly on the ratio between amplitude of the shear stress loading and the background normal stress. We define a range of ratio indicative of the occurrence of the triggering. We later test the triggering of the instability using the shear stress history from 44 large teleseismic earthquakes (data equivalent to those used in Chapter 1). With the constraints of these observations, we find that the background normal stress should be in the range of ˜400-700 kPa. The background normal stress suggested agrees with the common hypothesis that the tremor source is under low normal stress. In addition, our results provide a first estimation of the background normal stress with numerical method. We also demonstrate how our model find constrains on the background physical stress or frictional conditions, with several true incidences that transient shear stress triggers or not-triggers tremor. (Abstract shortened by UMI.).

  13. Correlation-based model of artificially induced plasticity in motor cortex by a bidirectional brain-computer interface.

    PubMed

    Lajoie, Guillaume; Krouchev, Nedialko I; Kalaska, John F; Fairhall, Adrienne L; Fetz, Eberhard E

    2017-02-01

    Experiments show that spike-triggered stimulation performed with Bidirectional Brain-Computer-Interfaces (BBCI) can artificially strengthen connections between separate neural sites in motor cortex (MC). When spikes from a neuron recorded at one MC site trigger stimuli at a second target site after a fixed delay, the connections between sites eventually strengthen. It was also found that effective spike-stimulus delays are consistent with experimentally derived spike-timing-dependent plasticity (STDP) rules, suggesting that STDP is key to drive these changes. However, the impact of STDP at the level of circuits, and the mechanisms governing its modification with neural implants remain poorly understood. The present work describes a recurrent neural network model with probabilistic spiking mechanisms and plastic synapses capable of capturing both neural and synaptic activity statistics relevant to BBCI conditioning protocols. Our model successfully reproduces key experimental results, both established and new, and offers mechanistic insights into spike-triggered conditioning. Using analytical calculations and numerical simulations, we derive optimal operational regimes for BBCIs, and formulate predictions concerning the efficacy of spike-triggered conditioning in different regimes of cortical activity.

  14. Correlation-based model of artificially induced plasticity in motor cortex by a bidirectional brain-computer interface

    PubMed Central

    Lajoie, Guillaume; Kalaska, John F.; Fairhall, Adrienne L.; Fetz, Eberhard E.

    2017-01-01

    Experiments show that spike-triggered stimulation performed with Bidirectional Brain-Computer-Interfaces (BBCI) can artificially strengthen connections between separate neural sites in motor cortex (MC). When spikes from a neuron recorded at one MC site trigger stimuli at a second target site after a fixed delay, the connections between sites eventually strengthen. It was also found that effective spike-stimulus delays are consistent with experimentally derived spike-timing-dependent plasticity (STDP) rules, suggesting that STDP is key to drive these changes. However, the impact of STDP at the level of circuits, and the mechanisms governing its modification with neural implants remain poorly understood. The present work describes a recurrent neural network model with probabilistic spiking mechanisms and plastic synapses capable of capturing both neural and synaptic activity statistics relevant to BBCI conditioning protocols. Our model successfully reproduces key experimental results, both established and new, and offers mechanistic insights into spike-triggered conditioning. Using analytical calculations and numerical simulations, we derive optimal operational regimes for BBCIs, and formulate predictions concerning the efficacy of spike-triggered conditioning in different regimes of cortical activity. PMID:28151957

  15. A Mechanical Switch Couples T Cell Receptor Triggering to the Cytoplasmic Juxtamembrane Regions of CD3ζζ.

    PubMed

    Lee, Mark S; Glassman, Caleb R; Deshpande, Neha R; Badgandi, Hemant B; Parrish, Heather L; Uttamapinant, Chayasith; Stawski, Philipp S; Ting, Alice Y; Kuhns, Michael S

    2015-08-18

    The eight-subunit T cell receptor (TCR)-CD3 complex is the primary determinant for T cell fate decisions. Yet how it relays ligand-specific information across the cell membrane for conversion to chemical signals remains unresolved. We hypothesized that TCR engagement triggers a change in the spatial relationship between the associated CD3ζζ subunits at the junction where they emerge from the membrane into the cytoplasm. Using three in situ proximity assays based on ID-PRIME, FRET, and EPOR activity, we determined that the cytosolic juxtamembrane regions of the CD3ζζ subunits are spread apart upon assembly into the TCR-CD3 complex. TCR engagement then triggered their apposition. This mechanical switch resides upstream of the CD3ζζ intracellular motifs that initiate chemical signaling, as well as the polybasic stretches that regulate signal potentiation. These findings provide a framework from which to examine triggering events for activating immune receptors and other complex molecular machines. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Bifunctional ultraviolet/ultrasound responsive composite TiO2/polyelectrolyte microcapsules

    NASA Astrophysics Data System (ADS)

    Gao, Hui; Wen, Dongsheng; Tarakina, Nadezda V.; Liang, Jierong; Bushby, Andy J.; Sukhorukov, Gleb B.

    2016-02-01

    Designing and fabricating multifunctional microcapsules are of considerable interest in both academic and industrial research aspects. This work reports an innovative approach to fabricate composite capsules with high UV and ultrasound responsive functionalities that can be used as external triggers for controlled release, yet with enhanced mechanical strength that can make them survive in a harsh environment. Needle-like TiO2 nanoparticles (NPs) were produced in situ into layer-by-layer (LbL) polyelectrolyte (PE) shells through the hydrolysis of titanium butoxide (TIBO). These rigid TiO2 NPs yielded the formed capsules with excellent mechanical strength, showing a free standing structure. A possible mechanism is proposed for the special morphology formation of the TiO2 NPs and their reinforcing effects. Synergistically, their response to UV and ultrasound was visualized via SEM, with the results showing an irreversible shell rapture upon exposure to either UV or ultrasound irradiation. As expected, the release studies revealed that the dextran release from the TiO2/PE capsules was both UV-dependent and ultrasound-dependent. Besides, the biocompatibility of the capsules with the incorporation of amorphous TiO2 NPs was confirmed by an MTT assay experiment. All these pieces of evidence suggested a considerable potential medicinal application of TiO2/PE capsules for controlled drug delivery.Designing and fabricating multifunctional microcapsules are of considerable interest in both academic and industrial research aspects. This work reports an innovative approach to fabricate composite capsules with high UV and ultrasound responsive functionalities that can be used as external triggers for controlled release, yet with enhanced mechanical strength that can make them survive in a harsh environment. Needle-like TiO2 nanoparticles (NPs) were produced in situ into layer-by-layer (LbL) polyelectrolyte (PE) shells through the hydrolysis of titanium butoxide (TIBO). These rigid TiO2 NPs yielded the formed capsules with excellent mechanical strength, showing a free standing structure. A possible mechanism is proposed for the special morphology formation of the TiO2 NPs and their reinforcing effects. Synergistically, their response to UV and ultrasound was visualized via SEM, with the results showing an irreversible shell rapture upon exposure to either UV or ultrasound irradiation. As expected, the release studies revealed that the dextran release from the TiO2/PE capsules was both UV-dependent and ultrasound-dependent. Besides, the biocompatibility of the capsules with the incorporation of amorphous TiO2 NPs was confirmed by an MTT assay experiment. All these pieces of evidence suggested a considerable potential medicinal application of TiO2/PE capsules for controlled drug delivery. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06666b

  17. Detection and enforcement of failure-to-yield in an emergency vehicle preemption system

    NASA Technical Reports Server (NTRS)

    Bachelder, Aaron (Inventor); Wickline, Richard (Inventor)

    2007-01-01

    An intersection controlled by an intersection controller receives trigger signals from on-coming emergency vehicles responding to an emergency call. The intersection controller initiates surveillance of the intersection via cameras installed at the intersection in response to a received trigger signal. The surveillance may begin immediately upon receipt of the trigger signal from an emergency vehicle, or may wait until the intersection controller determines that the signaling emergency vehicle is in the field of view of the cameras at the intersection. Portions of the captured images are tagged by the intersection controller based on tag signals transmitted by the vehicle or based on detected traffic patterns that indicate a potential traffic violation. The captured images are downloaded to a processing facility that analyzes the images and automatically issues citations for captured traffic violations.

  18. Eye motion triggered self-powered mechnosensational communication system using triboelectric nanogenerator.

    PubMed

    Pu, Xianjie; Guo, Hengyu; Chen, Jie; Wang, Xue; Xi, Yi; Hu, Chenguo; Wang, Zhong Lin

    2017-07-01

    Mechnosensational human-machine interfaces (HMIs) can greatly extend communication channels between human and external devices in a natural way. The mechnosensational HMIs based on biopotential signals have been developing slowly owing to the low signal-to-noise ratio and poor stability. In eye motions, the corneal-retinal potential caused by hyperpolarization and depolarization is very weak. However, the mechanical micromotion of the skin around the corners of eyes has never been considered as a good trigger signal source. We report a novel triboelectric nanogenerator (TENG)-based micromotion sensor enabled by the coupling of triboelectricity and electrostatic induction. By using an indium tin oxide electrode and two opposite tribomaterials, the proposed flexible and transparent sensor is capable of effectively capturing eye blink motion with a super-high signal level (~750 mV) compared with the traditional electrooculogram approach (~1 mV). The sensor is fixed on a pair of glasses and applied in two real-time mechnosensational HMIs-the smart home control system and the wireless hands-free typing system with advantages of super-high sensitivity, stability, easy operation, and low cost. This TENG-based micromotion sensor is distinct and unique in its fundamental mechanism, which provides a novel design concept for intelligent sensor technique and shows great potential application in mechnosensational HMIs.

  19. Tissue factor expression by endothelial cells in sickle cell anemia.

    PubMed

    Solovey, A; Gui, L; Key, N S; Hebbel, R P

    1998-05-01

    The role of the vascular endothelium in activation of the coagulation system, a fundamental homeostatic mechanism of mammalian biology, is uncertain because there is little evidence indicating that endothelial cells in vivo express tissue factor (TF), the system's triggering mechanism. As a surrogate for vessel wall endothelium, we examined circulating endothelial cells (CEC) from normals and patients with sickle cell anemia, a disease associated with activation of coagulation. We find that sickle CEC abnormally express TF antigen (expressed as percent CEC that are TF-positive), with 66+/-13% positive in sickle patients in steady-state, 83+/-19% positive in sickle patients presenting with acute vasoocclusive episodes, and only 10+/-13% positive in normal controls. Repeated samplings confirmed this impression that TF expression is greater when sickle patients develop acute vasoocclusive episodes. Sickle CEC are also positive for TF mRNA, with excellent concurrence between antigen and mRNA expression. The TF expressed on the antigen-positive CEC is functional, as demonstrated by a binding assay for Factor VIIa and a chromogenic assay sensitive to generation of Factor Xa. By establishing that endothelial cells in vivo can express TF, these data imply that the vast endothelial surface area does provide an important pathophysiologic trigger for coagulation activation.

  20. Eye motion triggered self-powered mechnosensational communication system using triboelectric nanogenerator

    PubMed Central

    Pu, Xianjie; Guo, Hengyu; Chen, Jie; Wang, Xue; Xi, Yi; Hu, Chenguo; Wang, Zhong Lin

    2017-01-01

    Mechnosensational human-machine interfaces (HMIs) can greatly extend communication channels between human and external devices in a natural way. The mechnosensational HMIs based on biopotential signals have been developing slowly owing to the low signal-to-noise ratio and poor stability. In eye motions, the corneal-retinal potential caused by hyperpolarization and depolarization is very weak. However, the mechanical micromotion of the skin around the corners of eyes has never been considered as a good trigger signal source. We report a novel triboelectric nanogenerator (TENG)–based micromotion sensor enabled by the coupling of triboelectricity and electrostatic induction. By using an indium tin oxide electrode and two opposite tribomaterials, the proposed flexible and transparent sensor is capable of effectively capturing eye blink motion with a super-high signal level (~750 mV) compared with the traditional electrooculogram approach (~1 mV). The sensor is fixed on a pair of glasses and applied in two real-time mechnosensational HMIs—the smart home control system and the wireless hands-free typing system with advantages of super-high sensitivity, stability, easy operation, and low cost. This TENG-based micromotion sensor is distinct and unique in its fundamental mechanism, which provides a novel design concept for intelligent sensor technique and shows great potential application in mechnosensational HMIs. PMID:28782029

  1. Positional circulatory control in the sleeping infant and toddler: role of the inner ear and arterial pulse pressure.

    PubMed

    Cohen, Gary; Vella, Silvano; Jeffery, Heather; Lagercrantz, Hugo; Katz-Salamon, Miriam

    2012-08-01

    Heart rate (HR) and arterial blood pressure (BP) are rapidly and reflexively adjusted as body position and the force/direction of gravity alters. Anomalies in these mechanisms may predispose to circulatory failure during sleep. We analysed the development of two key reflexes involved by undertaking a longitudinal (birth–1 year) comparison of instantaneous HR and BP changes evoked by abrupt upright, sideways or horizontal repositioning. Each manoeuvre triggered an identical rise in HR (tachycardia) followed by a slower rise in diastolic blood pressure (DBP)/systolic blood pressure (SBP) and variable pulse pressure (PP) change. We show that tachycardia is triggered by acceleration (vestibular) sensors located in the inner ear and slight changes in the pulsatile component of BP then signal to the arterial baroreceptors to reinforce or oppose these actions as needed. We also identified a PP anomaly in sleeping 1-year-olds of smokers that prematurely slows HR and is associated with mild positional hypotension. We conclude that positional circulatory compensation is initiated pre-emptively in a feed-forward manner and that feedback changes in vago-sympathetic drive to the heart (and perhaps blood vessels) by PP exert a slower but powerful modulating effect. An anomaly in either or both mechanisms may weaken positional compensation in some sleeping infants.

  2. A cybernetic view on wind-up.

    PubMed

    Farajidavar, Aydin; Gharibzadeh, Shahriar; Towhidkhah, Farzad; Saeb, Sohrab

    2006-01-01

    Wind-up is described traditionally as a frequency dependent increase in the excitability of spinal cord neurons, evoked by electrical stimulation of afferent C-fibers. Different kinds of wind-up have been reported, but wind-up of Abeta fibers in hyperalgesic states has gained little attention. In this paper, we present a cybernetic view on Abeta fiber wind-up and consider the involved molecular mechanisms as feedback and feedforward processes. Furthermore, our previous hypothesis, the sprouting phenomenon, is included in this view. Considering the proposed model, wind-up in hyperalgesic states might leave out in three different ways: (1) blocking the NMDA receptors by increasing extracellular Mg2+, 2) blocking the receptors and channels that contribute to Ca2+ inward current, and 3) blocking the Abeta fibers by local anesthetics. It seems that wind-up may be inhibited more effectively by using these three blocking mechanisms simultaneously, because in this case, the feedback process (main controller), the feedforward process (trigger), and Abeta stimulation (trigger) would be inhibited concurrently. Wind up may aggravate the pain in clinical hyperalgesic situations such as post-surgical states, some neuropathic pains, fibromyalgia syndrome, and post-herpetic neuralgia. Surely, clinical studies are needed to validate the effectiveness of our abovementioned suggestions in relieving such clinical pains.

  3. Double-edged effect of electric field on the mechanical property of water-filled carbon nanotubes with an application to nanoscale trigger.

    PubMed

    Ye, Hongfei; Zheng, Yonggang; Zhou, Lili; Zhao, Junfei; Zhang, Hong Wu; Chen, Zhen

    2017-11-08

    Polar water molecules would exhibit extraordinary phenomena under nanoscale confinement. By means of electric field, the water-filled carbon nanotube (CNT) that has been successfully fabricated in laboratory is expected to make distinct responses to the external electricity. Here, we examine the effect of electric field direction on the mechanical property of water-filled CNTs. It is found that the longitudinal electric field enhances but the transversal electric field reduces the elastic modulus and critical buckling stress of water-filled CNTs. The double-edged effect of electric field is attributed to the competition between the axial and circumferential pressures induced by polar water molecules. Furthermore, it is notable that the transversal electric field could result in an internal pressure with elliptical distribution, which is an effective and convenient approach to apply the nonuniform pressure on nanochannels. Based on a pre-strained water-filled CNTs, we design a nanoscale trigger with the evident and rapid height change started through switching the direction of electric field. The reported finding lays a foundation for the electricity-controlled property of nanochannels filled with polar molecules and provides an insight into the design of nanoscale functional devices. © 2017 IOP Publishing Ltd.

  4. BRAF-mutated cells activate GCN2-mediated integrated stress response as a cytoprotective mechanism in response to vemurafenib.

    PubMed

    Nagasawa, Ikuko; Kunimasa, Kazuhiro; Tsukahara, Satomi; Tomida, Akihiro

    2017-01-22

    In BRAF-mutated melanoma cells, the BRAF inhibitor, vemurafenib, induces phosphorylation of eukaryotic initiation factor 2α (eIF2α) and subsequent induction of activating transcription factor 4 (ATF4), the central regulation node of the integrated stress response (ISR). While the ISR supports cellular adaptation to various stresses, the role of vemurafenib-triggered ISR has not been fully characterized. Here, we showed that in response to vemurafenib, BRAF-mutated melanoma and colorectal cancer cells rapidly induced the ISR as a cytoprotective mechanism through activation of general control nonderepressible 2 (GCN2), an eIF2α kinase sensing amino acid levels. The vemurafenib-triggered ISR, an event independent of downstream MEK inhibition, was specifically prevented by silencing GCN2, but not other eIF2α kinases, including protein kinase-like endoplasmic reticulum kinase, which transmits endoplasmic reticulum (ER) stress. Consistently, the ER stress gatekeeper, GRP78, was not induced by vemurafenib. Interestingly, ATF4 silencing by siRNA rendered BRAF-mutated melanoma cells sensitive to vemurafenib. Thus, the GCN2-mediated ISR can promote cellular adaptation to vemurafenib-induced stress, providing an insight into the development of drug resistance. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Investigating MALDI MSI parameters (Part 2) - On the use of a mechanically shuttered trigger system for improved laser energy stability.

    PubMed

    Steven, Rory T; Dexter, Alex; Bunch, Josephine

    2016-07-15

    Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is now widely used to desorb, ionize and detect molecules from complex samples and tissue sections. The detected ion intensity within MALDI MS and MSI is intimately linked to the laser energy per pulse incident upon the sample during analysis. Laser energy/power stability can be significantly affected by the manner in which the laser is operated. High-repetition rate diode-pumped solid-state (DPSS) lasers are being increasingly adopted to enable high-throughput MALDI MSI analysis. Within this work two different laser-triggering setups are used to demonstrate the effect of laser energy instabilities due to spiking and thermal control phenomena and a setup with a shutter to remove these effects. The effect of non-equilibrium laser operation on MALDI MSI data versus the more stable laser pulse energy of the shutter-triggered system is demonstrated in thin films of α-cyano-4-hydroxycinnamic acid (CHCA) and for imaging of murine brain tissue sections. Significant unwanted variations in absolute and relative detected ion intensity are shown where energy variation is introduced by these phenomena, which return to equilibrium within the setup employed here over timescales relevant to MALDI MS analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Protons Trigger Mitochondrial Flashes.

    PubMed

    Wang, Xianhua; Zhang, Xing; Huang, Zhanglong; Wu, Di; Liu, Beibei; Zhang, Rufeng; Yin, Rongkang; Hou, Tingting; Jian, Chongshu; Xu, Jiejia; Zhao, Yan; Wang, Yanru; Gao, Feng; Cheng, Heping

    2016-07-26

    Emerging evidence indicates that mitochondrial flashes (mitoflashes) are highly conserved elemental mitochondrial signaling events. However, which signal controls their ignition and how they are integrated with other mitochondrial signals and functions remain elusive. In this study, we aimed to further delineate the signal components of the mitoflash and determine the mitoflash trigger mechanism. Using multiple biosensors and chemical probes as well as label-free autofluorescence, we found that the mitoflash reflects chemical and electrical excitation at the single-organelle level, comprising bursting superoxide production, oxidative redox shift, and matrix alkalinization as well as transient membrane depolarization. Both electroneutral H(+)/K(+) or H(+)/Na(+) antiport and matrix proton uncaging elicited immediate and robust mitoflash responses over a broad dynamic range in cardiomyocytes and HeLa cells. However, charge-uncompensated proton transport, which depolarizes mitochondria, caused the opposite effect, and steady matrix acidification mildly inhibited mitoflashes. Based on a numerical simulation, we estimated a mean proton lifetime of 1.42 ns and diffusion distance of 2.06 nm in the matrix. We conclude that nanodomain protons act as a novel, to our knowledge, trigger of mitoflashes in energized mitochondria. This finding suggests that mitoflash genesis is functionally and mechanistically integrated with mitochondrial energy metabolism. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  7. Structural mechanism for the carriage and release of thyroxine in the blood.

    PubMed

    Zhou, Aiwu; Wei, Zhenquan; Read, Randy J; Carrell, Robin W

    2006-09-05

    The hormones that most directly control tissue activities in health and disease are delivered by two noninhibitory members of the serpin family of protease inhibitors, thyroxine-binding globulin (TBG) and corticosteroid-binding globulin. The structure of TBG bound to tetra-iodo thyroxine, solved here at 2.8 A, shows how the thyroxine is carried in a surface pocket on the molecule. This unexpected binding site is confirmed by mutations associated with a loss of hormone binding in both TBG and also homologously in corticosteroid-binding globulin. TBG strikingly differs from other serpins in having the upper half of its main beta-sheet fully opened, so its reactive center peptide loop can readily move in and out of the sheet to give an equilibrated binding and release of thyroxine. The entry of the loop triggers a conformational change, with a linked contraction of the binding pocket and release of the bound thyroxine. The ready reversibility of this change is due to the unique presence in the reactive loop of TBG of a proline that impedes the full and irreversible entry of the loop that occurs in other serpins. Thus, TBG has adapted the serpin inhibitory mechanism to give a reversible flip-flop transition, from a high-affinity to a low-affinity form. The complexity and ready triggering of this conformational mechanism strongly indicates that TBG has evolved to allow a modulated and targeted delivery of thyroxine to the tissues.

  8. Development of an externally powered prosthetic hook for amputees

    NASA Technical Reports Server (NTRS)

    Karchak, A., Jr.; Allen, J. R.; Bontrager, E. L.

    1973-01-01

    The powered hook with trigger finger appears to be a useful adaptation of a terminal device for an amputee when performing vocational activities involving the use of a powered tool requiring a trigger control. The proportional control system includes transducers and amplifiers and appears to have widespread application for control of any external power, whether it be in the orthotic or prosthetic field.

  9. Innate Immune Control of West Nile Virus Infection

    PubMed Central

    Arjona, Alvaro; Wang, Penghua; Montgomery, Ruth R.; Fikrig, Erol

    2011-01-01

    West Nile virus (WNV), from the Flaviviridae family, is a re-emerging zoonotic pathogen of medical importance. In humans, WNV infection may cause life-threatening meningoencephalitis or long-term neurologic sequelae. WNV is transmitted by Culex spp mosquitoes and both the arthropod vector and the mammalian host are equipped with antiviral innate immune mechanisms sharing a common phylogeny. As far as the current evidence is able to demonstrate, mosquitoes primarily rely on RNA interference, Toll, Imd and JAK-STAT signaling pathways for limiting viral infection, while mammals are provided with these and other more complex antiviral mechanisms involving antiviral effectors, inflammatory mediators, and cellular responses triggered by highly specialized pathogen detection mechanisms that often resemble their invertebrate ancestry. This mini-review summarizes our current understanding of how the innate immune systems of the vector and the mammalian host react to WNV infection and shape its pathogenesis. PMID:21790942

  10. Modulation of UK lightning by heliospheric magnetic field polarity

    NASA Astrophysics Data System (ADS)

    Owens, M. J.; Scott, C. J.; Lockwood, M.; Barnard, L.; Harrison, R. G.; Nicoll, K.; Watt, C.; Bennett, A. J.

    2014-11-01

    Observational studies have reported solar magnetic modulation of terrestrial lightning on a range of time scales, from days to decades. The proposed mechanism is two-step: lightning rates vary with galactic cosmic ray (GCR) flux incident on Earth, either via changes in atmospheric conductivity and/or direct triggering of lightning. GCR flux is, in turn, primarily controlled by the heliospheric magnetic field (HMF) intensity. Consequently, global changes in lightning rates are expected. This study instead considers HMF polarity, which doesn't greatly affect total GCR flux. Opposing HMF polarities are, however, associated with a 40-60% difference in observed UK lightning and thunder rates. As HMF polarity skews the terrestrial magnetosphere from its nominal position, this perturbs local ionospheric potential at high latitudes and local exposure to energetic charged particles from the magnetosphere. We speculate as to the mechanism(s) by which this may, in turn, redistribute the global location and/or intensity of thunderstorm activity.

  11. Regulation of insulin exocytosis by calcium-dependent protein kinase C in beta cells.

    PubMed

    Trexler, Adam J; Taraska, Justin W

    2017-11-01

    The control of insulin release from pancreatic beta cells helps ensure proper blood glucose level, which is critical for human health. Protein kinase C has been shown to be one key control mechanism for this process. After glucose stimulation, calcium influx into beta cells triggers exocytosis of insulin-containing dense-core granules and activates protein kinase C via calcium-dependent phospholipase C-mediated generation of diacylglycerol. Activated protein kinase C potentiates insulin release by enhancing the calcium sensitivity of exocytosis, likely by affecting two main pathways that could be linked: (1) the reorganization of the cortical actin network, and (2) the direct phosphorylation of critical exocytotic proteins such as munc18, SNAP25, and synaptotagmin. Here, we review what is currently known about the molecular mechanisms of protein kinase C action on each of these pathways and how these effects relate to the control of insulin release by exocytosis. We identify remaining challenges in the field and suggest how these challenges might be addressed to advance our understanding of the regulation of insulin release in health and disease. Published by Elsevier Ltd.

  12. Autophagic degradation of dBruce controls DNA fragmentation in nurse cells during late Drosophila melanogaster oogenesis.

    PubMed

    Nezis, Ioannis P; Shravage, Bhupendra V; Sagona, Antonia P; Lamark, Trond; Bjørkøy, Geir; Johansen, Terje; Rusten, Tor Erik; Brech, Andreas; Baehrecke, Eric H; Stenmark, Harald

    2010-08-23

    Autophagy is an evolutionarily conserved pathway responsible for degradation of cytoplasmic material via the lysosome. Although autophagy has been reported to contribute to cell death, the underlying mechanisms remain largely unknown. In this study, we show that autophagy controls DNA fragmentation during late oogenesis in Drosophila melanogaster. Inhibition of autophagy by genetically removing the function of the autophagy genes atg1, atg13, and vps34 resulted in late stage egg chambers that contained persisting nurse cell nuclei without fragmented DNA and attenuation of caspase-3 cleavage. The Drosophila inhibitor of apoptosis (IAP) dBruce was found to colocalize with the autophagic marker GFP-Atg8a and accumulated in autophagy mutants. Nurse cells lacking Atg1 or Vps34 in addition to dBruce contained persisting nurse cell nuclei with fragmented DNA. This indicates that autophagic degradation of dBruce controls DNA fragmentation in nurse cells. Our results reveal autophagic degradation of an IAP as a novel mechanism of triggering cell death and thereby provide a mechanistic link between autophagy and cell death.

  13. Engineering controllable bidirectional molecular motors based on myosin

    PubMed Central

    Chen, Lu; Nakamura, Muneaki; Schindler, Tony D.; Parker, David; Bryant, Zev

    2012-01-01

    Cytoskeletal motors drive the transport of organelles and molecular cargoes within cells1, and have potential applications in molecular detection and diagnostic devices2,3. Engineering molecular motors with dynamically controllable properties will allow selective perturbation of mechanical processes in living cells, and yield optimized device components for complex tasks such as molecular sorting and directed assembly3. Biological motors have previously been modified by introducing activation/deactivation switches that respond to metal ions4,5 and other signals6. Here we show that myosin motors can be engineered to reversibly change their direction of motion in response to a calcium signal. Building on previous protein engineering studies7–11 and guided by a structural model12 for the redirected power stroke of myosin VI, we constructed bidirectional myosins through the rigid recombination of structural modules. The performance of the motors was confirmed using gliding filament assays and single fluorophore tracking. Our general strategy, in which external signals trigger changes in the geometry and mechanics of myosin lever arms, should enable spatiotemporal control over a range of motor properties including processivity, stride size13, and branchpoint turning14. PMID:22343382

  14. A Constitutive Model for Strain-Controlled Strength Degradation of Rockmasses (SDR)

    NASA Astrophysics Data System (ADS)

    Kalos, A.; Kavvadas, M.

    2017-11-01

    The paper describes a continuum, rate-independent, incremental plasticity constitutive model applicable in weak rocks and heavily fractured rockmasses, where mechanical behaviour is controlled by rockmass strength rather than structural features (discontinuities). The model describes rockmass structure by a generalised Hoek-Brown Structure Envelope (SE) in the stress space. Stress paths inside the SE are nonlinear and irreversible to better simulate behaviour at strains up to peak strength and under stress reversals. Stress paths on the SE have user-controlled volume dilatancy (gradually reducing to zero at large shear strains) and can model post-peak strain softening of brittle rockmasses via a structure degradation (damage) mechanism triggered by accumulated plastic shear strains. As the SE may strain harden with plastic strains, ductile behaviour can also be modelled. The model was implemented in the Finite Element Code Simulia ABAQUS and was applied in plane strain (2D) excavation of a cylindrical cavity (tunnel) to predict convergence-confinement curves. It is shown that small-strain nonlinearity, variable volume dilatancy and post-peak hardening/softening strongly affect the predicted curves, resulting in corresponding differences of lining pressures in real tunnel excavations.

  15. Engineering controllable bidirectional molecular motors based on myosin

    NASA Astrophysics Data System (ADS)

    Chen, Lu; Nakamura, Muneaki; Schindler, Tony D.; Parker, David; Bryant, Zev

    2012-04-01

    Cytoskeletal motors drive the transport of organelles and molecular cargoes within cells and have potential applications in molecular detection and diagnostic devices. Engineering molecular motors with controllable properties will allow selective perturbation of mechanical processes in living cells and provide optimized device components for tasks such as molecular sorting and directed assembly. Biological motors have previously been modified by introducing activation/deactivation switches that respond to metal ions and other signals. Here, we show that myosin motors can be engineered to reversibly change their direction of motion in response to a calcium signal. Building on previous protein engineering studies and guided by a structural model for the redirected power stroke of myosin VI, we have constructed bidirectional myosins through the rigid recombination of structural modules. The performance of the motors was confirmed using gliding filament assays and single fluorophore tracking. Our strategy, in which external signals trigger changes in the geometry and mechanics of myosin lever arms, should make it possible to achieve spatiotemporal control over a range of motor properties including processivity, stride size and branchpoint turning.

  16. Roles of dynamical symmetry breaking in driving oblate-prolate transitions of atomic clusters

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

    Oka, Yurie, E-mail: ok-yu@fuji.waseda.jp; Yanao, Tomohiro, E-mail: yanao@waseda.jp; Koon, Wang Sang, E-mail: koon@cds.caltech.edu

    2015-04-07

    This paper explores the driving mechanisms for structural transitions of atomic clusters between oblate and prolate isomers. We employ the hyperspherical coordinates to investigate structural dynamics of a seven-atom cluster at a coarse-grained level in terms of the dynamics of three gyration radii and three principal axes, which characterize overall mass distributions of the cluster. Dynamics of gyration radii is governed by two kinds of forces. One is the potential force originating from the interactions between atoms. The other is the dynamical forces called the internal centrifugal forces, which originate from twisting and shearing motions of the system. The internalmore » centrifugal force arising from twisting motions has an effect of breaking the symmetry between two gyration radii. As a result, in an oblate isomer, activation of the internal centrifugal force that has the effect of breaking the symmetry between the two largest gyration radii is crucial in triggering structural transitions into prolate isomers. In a prolate isomer, on the other hand, activation of the internal centrifugal force that has the effect of breaking the symmetry between the two smallest gyration radii is crucial in triggering structural transitions into oblate isomers. Activation of a twisting motion that switches the movement patterns of three principal axes is also important for the onset of structural transitions between oblate and prolate isomers. Based on these trigger mechanisms, we finally show that selective activations of specific gyration radii and twisting motions, depending on the isomer of the cluster, can effectively induce structural transitions of the cluster. The results presented here could provide further insights into the control of molecular reactions.« less

  17. Autophagy Constitutes a Protective Mechanism against Ethanol Toxicity in Mouse Astrocytes and Neurons.

    PubMed

    Pla, Antoni; Pascual, María; Guerri, Consuelo

    2016-01-01

    Ethanol induces brain damage and neurodegeneration by triggering inflammatory processes in glial cells through activation of Toll-like receptor 4 (TLR4) signaling. Recent evidence indicates the role of protein degradation pathways in neurodegeneration and alcoholic liver disease, but how these processes affect the brain remains elusive. We have demonstrated that chronic ethanol consumption impairs proteolytic pathways in mouse brain, and the immune response mediated by TLR4 receptors participates in these dysfunctions. We evaluate the in vitro effects of an acute ethanol dose on the autophagy-lysosome pathway (ALP) on WT and TLR4-/- mouse astrocytes and neurons in primary culture, and how these changes affect cell survival. Our results show that ethanol induces overexpression of several autophagy markers (ATG12, LC3-II, CTSB), and increases the number of lysosomes in WT astrocytes, effects accompanied by a basification of lysosomal pH and by lowered phosphorylation levels of autophagy inhibitor mTOR, along with activation of complexes beclin-1 and ULK1. Notably, we found only minor changes between control and ethanol-treated TLR4-/- mouse astroglial cells. Ethanol also triggers the expression of the inflammatory mediators iNOS and COX-2, but induces astroglial death only slightly. Blocking autophagy by using specific inhibitors increases both inflammation and cell death. Conversely, in neurons, ethanol down-regulates the autophagy pathway and triggers cell death, which is partially recovered by using autophagy enhancers. These results support the protective role of the ALP against ethanol-induced astroglial cell damage in a TLR4-dependent manner, and provide new insight into the mechanisms that underlie ethanol-induced brain damage and are neuronal sensitive to the ethanol effects.

  18. Roles of dynamical symmetry breaking in driving oblate-prolate transitions of atomic clusters

    NASA Astrophysics Data System (ADS)

    Oka, Yurie; Yanao, Tomohiro; Koon, Wang Sang

    2015-04-01

    This paper explores the driving mechanisms for structural transitions of atomic clusters between oblate and prolate isomers. We employ the hyperspherical coordinates to investigate structural dynamics of a seven-atom cluster at a coarse-grained level in terms of the dynamics of three gyration radii and three principal axes, which characterize overall mass distributions of the cluster. Dynamics of gyration radii is governed by two kinds of forces. One is the potential force originating from the interactions between atoms. The other is the dynamical forces called the internal centrifugal forces, which originate from twisting and shearing motions of the system. The internal centrifugal force arising from twisting motions has an effect of breaking the symmetry between two gyration radii. As a result, in an oblate isomer, activation of the internal centrifugal force that has the effect of breaking the symmetry between the two largest gyration radii is crucial in triggering structural transitions into prolate isomers. In a prolate isomer, on the other hand, activation of the internal centrifugal force that has the effect of breaking the symmetry between the two smallest gyration radii is crucial in triggering structural transitions into oblate isomers. Activation of a twisting motion that switches the movement patterns of three principal axes is also important for the onset of structural transitions between oblate and prolate isomers. Based on these trigger mechanisms, we finally show that selective activations of specific gyration radii and twisting motions, depending on the isomer of the cluster, can effectively induce structural transitions of the cluster. The results presented here could provide further insights into the control of molecular reactions.

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

    Chen, Shiwei; Dong, Yushu; Xu, Chun

    Highlights: •MTA1 expression is upregulated in SCs upon MEHP treatment. •Knockdown of MTA1 in SCs impairs the MEHP-induced NFκB signaling activation. •Knockdown of MTA1 inhibits recruitment of NFκB onto FasL promoter in MEHP-treated SCs. -- Abstract: The Fas/FasL signaling pathway, controlled by nuclear factor-κB (NFκB) at the transcriptional level, is critical for triggering germ cell apoptosis in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC) injury, but the exact regulation mechanism remain unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), a component of the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs during themore » early recovery after MEHP exposure. This expression change was in line with the dynamic changes in germ cell apoptosis in response to MEHP treatment. Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP-induced early activation of NFκB pathway and abolish the recruitment of NFκB onto FasL promoter, which consequently diminished the MEHP-triggered FasL induction. Considering that Fas/FasL is a well characterized apoptosis initiating signaling during SCs injury, our results point to a potential “switch on” effect of MTA1, which may govern the activation of NFκB/FasL cascade in MEHP-insulted SCs. Overall, the MTA1/NFκB/FasL circuit may serve as an important defensive/repairing mechanism to help to control the germ cell quality after SCs injury.« less

  20. Glutathione Depletion Induced by c-Myc Downregulation Triggers Apoptosis on Treatment with Alkylating Agents1

    PubMed Central

    Biroccio, Annamaria; Benassi, Barbara; Fiorentino, Francesco; Zupi, Gabriella

    2004-01-01

    Abstract Here we investigate the mechanism(s) involved in the c-Myc-dependent drug response of melanoma cells. By using three M14-derived c-Myc low-expressing clones, we demonstrate that alkylating agents, cisplatin and melphalan, trigger apoptosis in the c-Myc antisense transfectants, but not in the parental line. On the contrary, topoisomerase inhibitors, adriamycin and camptothecin, induce apoptosis to the same extent regardless of c-Myc expression. Because we previously demonstrated that c-Myc downregulation decreases glutathione (GSH) content, we evaluated the role of GSH in the apoptosis induced by the different drugs. In control cells treated with one of the alkylating agents or the others, GSH depletion achieved by l-buthionine-sulfoximine preincubation opens the apoptotic pathway. The apoptosis proceeded through early Bax relocalization, cytochrome c release, and concomitant caspase-9 activation, whereas reactive oxygen species production and alteration of mitochondria membrane potential were late events. That GSH was determining in the c-Myc-dependent drug-induced apoptosis was demonstrated by altering the intracellular GSH content of the c-Myc low-expressing cells up to the level of controls. Indeed, GSH ethyl ester-mediated increase of GSH abrogated apoptosis induced by cisplatin and melphalan by inhibition of Bax/cytochrome c redistribution. The relationship among c-Myc, GSH content, and the response to alkylating agent has been also evaluated in the M14 Myc overexpressing clones as well as in the melanoma JR8 c-Myc antisense transfectants. All together, these results demonstrate that GSH plays a key role in governing c-Myc-dependent drug-induced apoptosis. PMID:15153331

  1. Light-activated control of protein channel assembly mediated by membrane mechanics

    NASA Astrophysics Data System (ADS)

    Miller, David M.; Findlay, Heather E.; Ces, Oscar; Templer, Richard H.; Booth, Paula J.

    2016-12-01

    Photochemical processes provide versatile triggers of chemical reactions. Here, we use a photoactivated lipid switch to modulate the folding and assembly of a protein channel within a model biological membrane. In contrast to the information rich field of water-soluble protein folding, there is only a limited understanding of the assembly of proteins that are integral to biological membranes. It is however possible to exploit the foreboding hydrophobic lipid environment and control membrane protein folding via lipid bilayer mechanics. Mechanical properties such as lipid chain lateral pressure influence the insertion and folding of proteins in membranes, with different stages of folding having contrasting sensitivities to the bilayer properties. Studies to date have relied on altering bilayer properties through lipid compositional changes made at equilibrium, and thus can only be made before or after folding. We show that light-activation of photoisomerisable di-(5-[[4-(4-butylphenyl)azo]phenoxy]pentyl)phosphate (4-Azo-5P) lipids influences the folding and assembly of the pentameric bacterial mechanosensitive channel MscL. The use of a photochemical reaction enables the bilayer properties to be altered during folding, which is unprecedented. This mechanical manipulation during folding, allows for optimisation of different stages of the component insertion, folding and assembly steps within the same lipid system. The photochemical approach offers the potential to control channel assembly when generating synthetic devices that exploit the mechanosensitive protein as a nanovalve.

  2. Self-recognition mechanism between skin and suckers prevents octopus arms from interfering with each other.

    PubMed

    Nesher, Nir; Levy, Guy; Grasso, Frank W; Hochner, Binyamin

    2014-06-02

    Controlling movements of flexible arms is a challenging task for the octopus because of the virtually infinite number of degrees of freedom (DOFs) [1, 2]. Octopuses simplify this control by using stereotypical motion patterns that reduce the DOFs, in the control space, to a workable few [2]. These movements are triggered by the brain and are generated by motor programs embedded in the peripheral neuromuscular system of the arm [3-5]. The hundreds of suckers along each arm have a tendency to stick to almost any object they contact [6-9]. The existence of this reflex could pose significant problems with unplanned interactions between the arms if not appropriately managed. This problem is likely to be accentuated because it is accepted that octopuses are "not aware of their arms" [10-14]. Here we report of a self-recognition mechanism that has a novel role in motor control, restraining the arms from interfering with each other. We show that the suckers of amputated arms never attach to octopus skin because a chemical in the skin inhibits the attachment reflex of the suckers. The peripheral mechanism appears to be overridden by central control because, in contrast to amputated arms, behaving octopuses sometime grab amputated arms. Surprisingly, octopuses seem to identify their own amputated arms, as they treat arms of other octopuses like food more often than their own. This self-recognition mechanism is a novel peripheral component in the embodied organization of the adaptive interactions between the octopus's brain, body, and environment [15, 16]. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Temporal Dynamics of Proactive and Reactive Motor Inhibition

    PubMed Central

    Liebrand, Matthias; Pein, Inga; Tzvi, Elinor; Krämer, Ulrike M.

    2017-01-01

    Proactive motor inhibition refers to endogenous preparatory mechanisms facilitating action inhibition, whereas reactive motor inhibition is considered to be a sudden stopping process triggered by external signals. Previous studies were inconclusive about the temporal dynamics of involved neurocognitive processes during proactive and reactive motor control. Using electroencephalography (EEG), we investigated the time-course of proactive and reactive inhibition, measuring event-related oscillations and event-related potentials (ERPs). Participants performed in a cued go/nogo paradigm with cues indicating whether the motor response might or might not have to be inhibited. Based on the dual mechanisms of control (DMC) framework by Braver, we investigated the role of attentional effects, motor preparation in the sensorimotor cortex and prefrontal cognitive control mechanisms, separating effects before and after target onset. In the cue-target interval, proactive motor inhibition was associated with increased attention, reflected in reduced visual alpha power and an increased contingent negative variation (CNV). At the same time, motor inhibition was modulated by reduced sensorimotor beta power. After target onset, proactive inhibition resulted in an increased N1, indicating allocation of attention towards relevant stimuli, increased prefrontal beta power and a modulation of sensorimotor mu activity. As in previous studies, reactive stopping of motor actions was associated with increased prefrontal beta power and increased sensorimotor beta activity. The results stress the relevance of attentional mechanisms for proactive inhibition and speak for different neurocognitive mechanisms being involved in the early preparation for and in later implementation of motor inhibition. PMID:28496405

  4. ChIP-seq reveals broad roles of SARD1 and CBP60g in regulating plant immunity.

    PubMed

    Sun, Tongjun; Zhang, Yaxi; Li, Yan; Zhang, Qian; Ding, Yuli; Zhang, Yuelin

    2015-12-18

    Recognition of pathogens by host plants leads to rapid transcriptional reprogramming and activation of defence responses. The expression of many defence regulators is induced in this process, but the mechanisms of how they are controlled transcriptionally are largely unknown. Here we use chromatin immunoprecipitation sequencing to show that the transcription factors SARD1 and CBP60g bind to the promoter regions of a large number of genes encoding key regulators of plant immunity. Among them are positive regulators of systemic immunity and signalling components for effector-triggered immunity and PAMP-triggered immunity, which is consistent with the critical roles of SARD1 and CBP60g in these processes. In addition, SARD1 and CBP60g target a number of genes encoding negative regulators of plant immunity, suggesting that they are also involved in negative feedback regulation of defence responses. Based on these findings we propose that SARD1 and CBP60g function as master regulators of plant immune responses.

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

    PubMed Central

    Michaud, Olivier

    2017-01-01

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

  6. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite

    PubMed Central

    Abizaid, Alfonso; Liu, Zhong-Wu; Andrews, Zane B.; Shanabrough, Marya; Borok, Erzsebet; Elsworth, John D.; Roth, Robert H.; Sleeman, Mark W.; Picciotto, Marina R.; Tschöp, Matthias H.; Gao, Xiao-Bing; Horvath, Tamas L.

    2006-01-01

    The gut hormone ghrelin targets the brain to promote food intake and adiposity. The ghrelin receptor growth hormone secretagogue 1 receptor (GHSR) is present in hypothalamic centers controlling energy metabolism as well as in the ventral tegmental area (VTA), a region important for motivational aspects of multiple behaviors, including feeding. Here we show that in mice and rats, ghrelin bound to neurons of the VTA, where it triggered increased dopamine neuronal activity, synapse formation, and dopamine turnover in the nucleus accumbens in a GHSR-dependent manner. Direct VTA administration of ghrelin also triggered feeding, while intra-VTA delivery of a selective GHSR antagonist blocked the orexigenic effect of circulating ghrelin and blunted rebound feeding following fasting. In addition, ghrelin- and GHSR-deficient mice showed attenuated feeding responses to restricted feeding schedules. Taken together, these data suggest that the mesolimbic reward circuitry is targeted by peripheral ghrelin to influence physiological mechanisms related to feeding. PMID:17060947

  7. Voltage gradients in solar array cavities as possible breakdown sites in spacecraft-charging-induced discharges

    NASA Technical Reports Server (NTRS)

    Stevens, N. J.; Mills, H. E.; Orange, L.

    1981-01-01

    A possible explanation for environmentally-induced discharges on geosynchronous satellites exists in the electric fields formed in the cavities between solar cells - the small gaps formed by the cover slides, solar cells, metallic interconnects and insulating substrate. When exposed to a substorm environment, the cover slides become less negatively charged than the spacecraft ground. If the resultant electric field becomes large enough, then the interconnect could emit electrons (probably by field emission) which could be accelerated to space by the positive voltage on the covers. An experimental study was conducted using a small solar array segment in which the interconnect potential was controlled by a power supply while the cover slides were irradiated by monoenergetic electrons. It was found that discharges could be triggered when the interconnect potential became at least 500 volts negative with respect to the cover slides. Analytical modeling of satellites exposed to substorm environments indicates that such gradients are possible. Therefore, it appears that this trigger mechanism for discharges is possible.

  8. New constraints on mechanisms of remotely triggered seismicity at Long Valley Caldera

    USGS Publications Warehouse

    Brodsky, E.E.; Prejean, S.G.

    2005-01-01

    Regional-scale triggering of local earthquakes in the crust by seismic waves from distant main shocks has now been robustly documented for over a decade. Some of the most thoroughly recorded examples of repeated triggering of a single site from multiple, large earthquakes are measured in geothermal fields of the western United States like Long Valley Caldera. As one of the few natural cases where the causality of an earthquake sequence is apparent, triggering provides fundamental constraints on the failure processes in earthquakes. We show here that the observed triggering by seismic waves is inconsistent with any mechanism that depends on cumulative shaking as measured by integrated energy density. We also present evidence for a frequency-dependent triggering threshold. On the basis of the seismic records of 12 regional and teleseismic events recorded at Long Valley Caldera, long-period waves (>30 s) are more effective at generating local seismicity than short-period waves of comparable amplitude. If the properties of the system are stationary over time, the failure threshold for long-period waves is ~0.05 cm/s vertical shaking. Assuming a phase velocity of 3.5 km/s and an elastic modulus of 3.5 x 1010Pa, the threshold in terms of stress is 5 kPa. The frequency dependence is due in part to the attenuation of the surface waves with depth. Fluid flow through a porous medium can produce the rest of the observed frequency dependence of the threshold. If the threshold is not stationary with time, pore pressures that are >99.5% of lithostatic and vary over time by a factor of 4 could explain the observations with no frequency dependence of the triggering threshold. Copyright 2005 by the American Geophysical Union.

  9. Linking turbidity current triggers to flow power, frequency and runout distances

    NASA Astrophysics Data System (ADS)

    Hizzett, J. L.; Hughes Clarke, J. E.; Cartigny, M.; Talling, P.; Sumner, E.; Clare, M. A.

    2017-12-01

    Submarine turbidity currents and terrestrial river systems are the two main processes for moving sediment across our planet, and it is important to understand how they are linked. Turbidity currents form thick deposits, burying large amounts of organic carbon, and posing a hazard to seabed pipelines and cables. It is essential to understand which initial trigger mechanisms produce the most frequent, powerful and longest runout turbidity currents, as these flows pose the greatest hazard for seafloor infrastructure (Cooper et al., 2013). Here were re-analyse the most detailed time-lapse mapping of a turbidity current system, which comprises 93 near-daily surveys collected by Hughes Clarke at Squamish Delta, British Columbia. It enables us to link different trigger mechanisms to flow properties such as runout distance. Turbidity currents at Squamish Delta are either triggered by submarine landslides or by sediment settling out from the river plume. Previously it was inferred that turbidity currents were most commonly triggered at river mouths by underwater landslides, or plunging (hyperpycnal) river discharge. However, here we show that turbidity currents are most commonly triggered by what we infer to be sediment settling from surface plumes (Hughes Clarke et al., 2014). We go on to show that turbidity currents initiated by settling from surface plumes can be as erosive and travel as far as landslide-triggered flows. We also find no relationship between submarine landslide volume and turbidity current runout. This is surprising because larger volume subaerial landslides tend to runout longer distances. We therefore show that the most hazardous turbidity currents at Squamish, which have the biggest impact on the seafloor, are initiated by sediment settling out from surface plumes, and not by large landslides as was previously expected.

  10. Neural Mechanisms Underlying Conscious and Unconscious Gaze-Triggered Attentional Orienting in Autism Spectrum Disorder

    PubMed Central

    Sato, Wataru; Kochiyama, Takanori; Uono, Shota; Yoshimura, Sayaka; Toichi, Motomi

    2017-01-01

    Impaired joint attention represents the core clinical feature of autism spectrum disorder (ASD). Behavioral studies have suggested that gaze-triggered attentional orienting is intact in response to supraliminally presented eyes but impaired in response to subliminally presented eyes in individuals with ASD. However, the neural mechanisms underlying conscious and unconscious gaze-triggered attentional orienting remain unclear. We investigated this issue in ASD and typically developing (TD) individuals using event-related functional magnetic resonance imaging. The participants viewed cue stimuli of averted or straight eye gaze direction presented either supraliminally or subliminally and then localized a target. Reaction times were shorter when eye-gaze cues were directionally valid compared with when they were neutral under the supraliminal condition in both groups; the same pattern was found in the TD group but not the ASD group under the subliminal condition. The temporo–parieto–frontal regions showed stronger activation in response to averted eyes than to straight eyes in both groups under the supraliminal condition. The left amygdala was more activated while viewing averted vs. straight eyes in the TD group than in the ASD group under the subliminal condition. These findings provide an explanation for the neural mechanisms underlying the impairment in unconscious but not conscious gaze-triggered attentional orienting in individuals with ASD and suggest possible neurological and behavioral interventions to facilitate their joint attention behaviors. PMID:28701942

  11. Dynamic Triggering around Fangshan Pluton near Beijing,China

    NASA Astrophysics Data System (ADS)

    Wang, W.; Gong, X.; Peng, Z.; Chen, Q.; Wu, C.

    2011-12-01

    Fangshan Pluton lies at SW of Beijing City and is formed at about 133-128Ma. The Pluton is surrounded by the NNE-trending Taihang mountain in the west as an "C" shape, and is in conjunction with the Northern China Plain along the Baobashan fault in the east. This region currently does not have abundant background seismicity, but previous studies (Peng et al., 2010, Wu et al. 2011) have shown that at least 4 major earthquakes in East Asia have triggered clear seismic events in this region. To further understand the dynamic triggering mechanism and improve the station coverage, we deployed the first batch temporal seismic array with 5 stations from 12/2008 to 7/2010 and the second batch with 11 stations around this area since 12/2010. Our temporary deployment was fortunate to capture the triggered seismicity following the 2011 Mw9.0 Tohoku-Oki, Japan, earthquake sequence. In this study, we use seismic data recorded by the permanent stations in the Capital Circle seismic network and our temporary deployment to investigate triggered seismicity following the 2010 Mw8.8 Chile earthquake and the Tohoku-Oki earthquake sequence. As was done before, we identify triggered earthquakes as impulsive seismic arrivals with clear P- and S-waves in 5 Hz high-pass-filtered three-component velocity seismograms and recorded by at least 3 stations. Most triggered earthquakes coincide with the large-amplitude Rayleigh waves. For the Tohoku-Oki case, we identify one weak event during the P-wave of the mainshock, and delayed triggering following the large-amplitude surface waves. In addition, triggered earthquakes can be seen in the Mw7.3 foreshock and mainshock of Tohoku earthquake, but not in aftershocks with 2 Mw>7.5 earthquakes in the following two months. These events mainly occurred at southwestern and western boundary region of the Pluton and are shallower (<5km) than normal earthquakes, which is similar to previous studies. Considering the abundant solution cavities and syncline/anticline structures developed during the magma intrusion, we suggest that the triggered earthquakes could occur at the weak boundary regions with abundant underground water that permeate into deep layer through the cracked syncline tips or faults. Our next step is to locate the triggered and background seismicity more precisely, and determine the focal mechanisms of the triggered events for better understanding of the source faults and necessary conditions for dynamic triggering in this region.

  12. Using Reflection Triggers while Learning in an Online Course

    ERIC Educational Resources Information Center

    Verpoorten, Dominique; Westera, Wim; Specht, Marcus

    2012-01-01

    This paper reports on a controlled experiment on the effects of three types of reflection triggers in an online course. Fifty-four volunteers, distributed in five groups, used these structured opportunities for reflection during learning. Results show that reflection triggers were extensively employed by the test persons and were perceived as…

  13. Optimal management of Ménière's disease.

    PubMed

    Foster, Carol A

    2015-01-01

    Confusion in the nomenclature of Ménière's disease and lack of a standard definition of the disorder until 1995 has hampered accurate assessment of treatment efficacy since the presently defined disorder was first described in 1938. The lack of a widely accepted mechanism of the disease has also delayed the development of rational treatments. Past treatments have focused on relieving elevated pressures in the hydropic ear and more recently on treatment of underlying migraine. Present dietary methods of control include sodium restriction and migraine trigger elimination. Pharmacologic treatments include diuretics, migraine prophylactic medications, histamine analogs, and oral steroids. Surgical procedures include intratympanic steroid perfusion, shunts, and ablative procedures when conservative treatments fail. External pressure devices are also used. Evidence of efficacy is lacking for most interventions other than ablation. At our institution, Ménière's disease is treated as a cerebrovascular disorder. Control of risk factors for cerebrovascular ischemia is combined with treatment of pressure dysfunction in the hydropic ear. Screening for risk factors is performed at presentation. Migraine, dyslipidemia, obesity, diabetes, sleep apnea, hypertension, and atherosclerosis are among the major factors that often require medical management. Migraine prophylactic medications, magnesium supplementation, sodium restriction, migraine trigger elimination, diuretics, anticoagulants, and antihypertensives are among the treatments used initially. Steroids administered orally or intratympanically are used if control is not achieved medically, and ablation remains the definitive treatment in unilateral cases experiencing treatment failure.

  14. Repeated intravenous doxapram induces phrenic motor facilitation

    PubMed Central

    Sandhu, MS; Lee, KZ; Gonzalez-Rothi, EJ; Fuller, DD

    2013-01-01

    Doxapram is a respiratory stimulant used to treat hypoventilation. Here we investigated whether doxapram could also trigger respiratory neuroplasticity. Specifically, we hypothesized that intermittent delivery of doxapram at low doses would lead to long-lasting increases (i.e., facilitation) of phrenic motor output in anesthetized, vagotomized, and mechanically-ventilated rats. Doxapram was delivered intravenously in a single bolus (2 or 6 mg/kg) or as a series of 3 injections (2 mg/kg) at 5 min intervals. Control groups received pH-matched saline injections (vehicle) or no treatment (anesthesia time control). Doxapram evoked an immediate increase in phrenic output in all groups, but a persistent increase in burst amplitude only occurred after repeated dosing with 2 mg/kg. At 60 min following the last injection, phrenic burst amplitude was 168±24% of baseline (%BL) in the group receiving 3 injections (P < 0.05 vs. controls), but was 103±8%BL and 112±4%BL in the groups receiving a single dose of 2 or 6 mg/kg, respectively. Following bilateral section of the carotid sinus nerves, the acute phrenic response to doxapram (2 mg/kg) was reduced by 68% suggesting that at low doses the drug was acting primarily via the carotid chemoreceptors. We conclude that intermittent application of doxapram can trigger phrenic neuroplasticity, and this approach might be of use in the context of respiratory rehabilitation following neurologic injury. PMID:24013015

  15. Research and Development of Information and Communication Technology-based Home Blood Pressure Monitoring from Morning to Nocturnal Hypertension.

    PubMed

    Kario, Kazuomi; Tomitani, Naoko; Matsumoto, Yuri; Hamasaki, Haruna; Okawara, Yukie; Kondo, Maiko; Nozue, Ryoko; Yamagata, Hiromi; Okura, Ayako; Hoshide, Satoshi

    2016-01-01

    Asians have specific characteristics of hypertension (HTN) and its relationship with cardiovascular disease. The morning surge in blood pressure (BP) in Asians is more extended, and the association slope between higher BP and the risk for cardiovascular events is steeper in this population than in whites. Thus, 24-hour BP control including at night and in the morning is especially important for Asian patients with HTN. There are 3 components of "perfect 24-hour BP control": the 24-hour BP level, adequate dipping of nocturnal BP (dipper type), and adequate BP variability such as the morning BP surge. The morning BP-guided approach using home BP monitoring (HBPM) is the first step toward perfect 24-hour BP control. After controlling morning HTN, nocturnal HTN is the second target. We have been developing HBPM that can measure nocturnal BP. First, we developed a semiautomatic HBPM device with the function of automatic fixed-interval BP measurement during sleep. In the J-HOP (Japan Morning Surge Home Blood Pressure) study, the largest nationwide home BP cohort, we successfully measured nocturnal home BP using this device with data memory, 3 times during sleep (2, 3, and 4 am), and found that nocturnal home BP is significantly correlated with organ damage independently of office and morning BP values. The second advance was the development of trigger nocturnal BP (TNP) monitoring with an added trigger function that initiates BP measurements when oxygen desaturation falls below a variable threshold continuously monitored by pulse oximetry. TNP can detect the specific nocturnal BP surges triggered by hypoxic episodes in patients with sleep apnea syndrome. We also added the lowest heart rate-trigger function to TNP to detect the "basal nocturnal BP," which is determined by the circulating volume and structural cardiovascular system without any increase in sympathetic tonus. This double TNP is a novel concept for evaluating the pathogenic pressor mechanism of nocturnal BP. These data are now collected using an information and communication technology (ICT)-based monitoring system. The BP variability includes different time-phase variability from the shortest beat-by-beat, positional, diurnal, day-by-day, visit-to-visit, seasonal, and the longest yearly changes. The synergistic resonance of each type of BP variability would produce great dynamic BP surges, which trigger cardiovascular events. Thus, in the future, the management of HTN based on the simultaneous assessment of the resonance of all of the BP variability phenotypes using a wearable "surge" BP monitoring device with an ICT-based data analysis system will contribute to the ultimate individualized medication for cardiovascular disease. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Spontaneous pre-stimulus fluctuations in the activity of right fronto-parietal areas influence inhibitory control performance

    PubMed Central

    Chavan, Camille F.; Manuel, Aurelie L.; Mouthon, Michael; Spierer, Lucas

    2013-01-01

    Inhibitory control refers to the ability to suppress planned or ongoing cognitive or motor processes. Electrophysiological indices of inhibitory control failure have been found to manifest even before the presentation of the stimuli triggering the inhibition, suggesting that pre-stimulus brain-states modulate inhibition performance. However, previous electrophysiological investigations on the state-dependency of inhibitory control were based on averaged event-related potentials (ERPs), a method eliminating the variability in the ongoing brain activity not time-locked to the event of interest. These studies thus left unresolved whether spontaneous variations in the brain-state immediately preceding unpredictable inhibition-triggering stimuli also influence inhibitory control performance. To address this question, we applied single-trial EEG topographic analyses on the time interval immediately preceding NoGo stimuli in conditions where the responses to NoGo trials were correctly inhibited [correct rejection (CR)] vs. committed [false alarms (FAs)] during an auditory spatial Go/NoGo task. We found a specific configuration of the EEG voltage field manifesting more frequently before correctly inhibited responses to NoGo stimuli than before FAs. There was no evidence for an EEG topography occurring more frequently before FAs than before CR. The visualization of distributed electrical source estimations of the EEG topography preceding successful response inhibition suggested that it resulted from the activity of a right fronto-parietal brain network. Our results suggest that the fluctuations in the ongoing brain activity immediately preceding stimulus presentation contribute to the behavioral outcomes during an inhibitory control task. Our results further suggest that the state-dependency of sensory-cognitive processing might not only concern perceptual processes, but also high-order, top-down inhibitory control mechanisms. PMID:23761747

  17. The efficacy of 95-Hz topical vibration in pain reduction for trigger finger injection: a placebo-controlled, prospective, randomized trial.

    PubMed

    Park, Kevin W; Boyer, Martin I; Calfee, Ryan P; Goldfarb, Charles A; Osei, Daniel A

    2014-11-01

    To determine whether vibratory stimulation would decrease pain experienced by patients during corticosteroid injection for trigger finger. A total of 90 trigger finger injections were randomized to 1 of 3 cohorts. With the injection, patients received no vibration (control group), ultrasound vibration (sham control group), or vibration (experimental group). We used a commercial handheld massaging device to provide a vibratory stimulus for the experimental group. We obtained visual analog scale (VAS) pain scores before and after injection to assess anticipated pain and actual pain experienced. Anticipated pain and actual pain did not differ significantly among groups. Anticipated VAS pain scores were 45, 48, and 50 and actual VAS pain scores were 56, 56, and 63 for the vibration, control, and sham control groups, respectively. When normalized using anchoring VAS pain scores for "stubbing a toe" or "paper cut," no between-group differences remained in injection pain scores. Concomitant vibratory stimulation does not reduce pain experienced during corticosteroid injections for trigger finger. Therapeutic I. Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  18. Buckligami: Actuation of soft structures through mechanical instabilities

    NASA Astrophysics Data System (ADS)

    Lazarus, Arnaud; Reis, Pedro

    2013-03-01

    We present a novel mechanism for actuating soft structures, that is triggered through buckling. Our elastomeric samples are rapid-prototyped using digital fabrication and comprise of a cylindrical shell patterned with an array of voids, each of which is covered by a thin membrane. Decreasing the internal pressure of the structure induces local buckling of the ligaments of the pattern, resulting in controllable folding of the global structure. Using rigid inclusions to plug the voids in specific geometric arrangements allows us to excite a variety of different fundamental motions of the cylindrical shell, including flexure and twist. We refer to this new mechanism of buckling-induced folding as ``buckligami.'' Given that geometry, elasticity and buckling are the underlying ingredients of this local folding mechanism, the global actuation is scalable, reversible and repeatable. Characterization and rationalization of our experiments provide crucial fundamental understanding to aid the design of new scale-independent actuators, with potential implications in the field of soft robotics.

  19. Proteostasis in cardiac health and disease.

    PubMed

    Henning, Robert H; Brundel, Bianca J J M

    2017-11-01

    The incidence and prevalence of cardiac diseases, which are the main cause of death worldwide, are likely to increase because of population ageing. Prevailing theories about the mechanisms of ageing feature the gradual derailment of cellular protein homeostasis (proteostasis) and loss of protein quality control as central factors. In the heart, loss of protein patency, owing to flaws in genetically-determined design or because of environmentally-induced 'wear and tear', can overwhelm protein quality control, thereby triggering derailment of proteostasis and contributing to cardiac ageing. Failure of protein quality control involves impairment of chaperones, ubiquitin-proteosomal systems, autophagy, and loss of sarcomeric and cytoskeletal proteins, all of which relate to induction of cardiomyocyte senescence. Targeting protein quality control to maintain cardiac proteostasis offers a novel therapeutic strategy to promote cardiac health and combat cardiac disease. Currently marketed drugs are available to explore this concept in the clinical setting.

  20. Controlling gain one photon at a time

    PubMed Central

    Schwartz, Gregory W; Rieke, Fred

    2013-01-01

    Adaptation is a salient property of sensory processing. All adaptational or gain control mechanisms face the challenge of obtaining a reliable estimate of the property of the input to be adapted to and obtaining this estimate sufficiently rapidly to be useful. Here, we explore how the primate retina balances the need to change gain rapidly and reliably when photons arrive rarely at individual rod photoreceptors. We find that the weakest backgrounds that decrease the gain of the retinal output signals are similar to those that increase human behavioral threshold, and identify a novel site of gain control in the retinal circuitry. Thus, surprisingly, the gain of retinal signals begins to decrease essentially as soon as background lights are detectable; under these conditions, gain control does not rely on a highly averaged estimate of the photon count, but instead signals from individual photon absorptions trigger changes in gain. DOI: http://dx.doi.org/10.7554/eLife.00467.001 PMID:23682314

  1. Interplay between population firing stability and single neuron dynamics in hippocampal networks

    PubMed Central

    Slomowitz, Edden; Styr, Boaz; Vertkin, Irena; Milshtein-Parush, Hila; Nelken, Israel; Slutsky, Michael; Slutsky, Inna

    2015-01-01

    Neuronal circuits' ability to maintain the delicate balance between stability and flexibility in changing environments is critical for normal neuronal functioning. However, to what extent individual neurons and neuronal populations maintain internal firing properties remains largely unknown. In this study, we show that distributions of spontaneous population firing rates and synchrony are subject to accurate homeostatic control following increase of synaptic inhibition in cultured hippocampal networks. Reduction in firing rate triggered synaptic and intrinsic adaptive responses operating as global homeostatic mechanisms to maintain firing macro-stability, without achieving local homeostasis at the single-neuron level. Adaptive mechanisms, while stabilizing population firing properties, reduced short-term facilitation essential for synaptic discrimination of input patterns. Thus, invariant ongoing population dynamics emerge from intrinsically unstable activity patterns of individual neurons and synapses. The observed differences in the precision of homeostatic control at different spatial scales challenge cell-autonomous theory of network homeostasis and suggest the existence of network-wide regulation rules. DOI: http://dx.doi.org/10.7554/eLife.04378.001 PMID:25556699

  2. Packet Scheduling Mechanism to Improve Quality of Short Flows and Low-Rate Flows

    NASA Astrophysics Data System (ADS)

    Yokota, Kenji; Asaka, Takuya; Takahashi, Tatsuro

    In recent years elephant flows are increasing by expansion of peer-to-peer (P2P) applications on the Internet. As a result, bandwidth is occupied by specific users triggering unfair resource allocation. The main packet-scheduling mechanism currently employed is first-in first-out (FIFO) where the available bandwidth of short flows is limited by elephant flows. Least attained service (LAS), which decides transfer priority of packets by the total amount of transferred data in all flows, was proposed to solve this problem. However, routers with LAS limit flows with large amount of transferred data even if they are low-rate. Therefore, it is necessary to improve the quality of low-rate flows with long holding times such as voice over Internet protocol (VoIP) applications. This paper proposes rate-based priority control (RBPC), which calculates the flow rate and control the priority by using it. Our proposed method can transfer short flows and low-rate flows in advance. Moreover, its fair performance is shown through simulations.

  3. Photothermally triggered actuation of hybrid materials as a new platform for in vitro cell manipulation

    DOE PAGES

    Sutton, Amy; Shirman, Tanya; Timonen, Jaakko V. I.; ...

    2017-03-13

    Mechanical forces in the cell’s natural environment have a crucial impact on growth, differentiation and behaviour. Few areas of biology can be understood without taking into account how both individual cells and cell networks sense and transduce physical stresses. However, the field is currently held back by the limitations of the available methods to apply physiologically relevant stress profiles on cells, particularly with sub-cellular resolution, in controlled in vitro experiments. Here we report a new type of active cell culture material that allows highly localized, directional and reversible deformation of the cell growth substrate, with control at scales ranging frommore » the entire surface to the subcellular, and response times on the order of seconds. These capabilities are not matched by any other method, and this versatile material has the potential to bridge the performance gap between the existing single cell micro-manipulation and 2D cell sheet mechanical stimulation techniques.« less

  4. Photothermally triggered actuation of hybrid materials as a new platform for in vitro cell manipulation

    PubMed Central

    Sutton, Amy; Shirman, Tanya; Timonen, Jaakko V. I.; England, Grant T; Kim, Philseok; Kolle, Mathias; Ferrante, Thomas; Zarzar, Lauren D; Strong, Elizabeth; Aizenberg, Joanna

    2017-01-01

    Mechanical forces in the cell’s natural environment have a crucial impact on growth, differentiation and behaviour. Few areas of biology can be understood without taking into account how both individual cells and cell networks sense and transduce physical stresses. However, the field is currently held back by the limitations of the available methods to apply physiologically relevant stress profiles on cells, particularly with sub-cellular resolution, in controlled in vitro experiments. Here we report a new type of active cell culture material that allows highly localized, directional and reversible deformation of the cell growth substrate, with control at scales ranging from the entire surface to the subcellular, and response times on the order of seconds. These capabilities are not matched by any other method, and this versatile material has the potential to bridge the performance gap between the existing single cell micro-manipulation and 2D cell sheet mechanical stimulation techniques. PMID:28287116

  5. Kinetochore-independent chromosome segregation driven by lateral microtubule bundles

    PubMed Central

    Muscat, Christina C; Torre-Santiago, Keila M; Tran, Michael V; Powers, James A; Wignall, Sarah M

    2015-01-01

    During cell division, chromosomes attach to spindle microtubules at sites called kinetochores, and force generated at the kinetochore-microtubule interface is the main driver of chromosome movement. Surprisingly, kinetochores are not required for chromosome segregation on acentrosomal spindles in Caenorhabditis elegans oocytes, but the mechanism driving chromosomes apart in their absence is not understood. In this study, we show that lateral microtubule–chromosome associations established during prometaphase remain intact during anaphase to facilitate separation, defining a novel form of kinetochore-independent segregation. Chromosome dynamics during congression and segregation are controlled by opposing forces; plus-end directed forces are mediated by a protein complex that forms a ring around the chromosome center and dynein on chromosome arms provides a minus-end force. At anaphase onset, ring removal shifts the balance between these forces, triggering poleward movement along lateral microtubule bundles. This represents an elegant strategy for controlling chromosomal movements during cell division distinct from the canonical kinetochore-driven mechanism. DOI: http://dx.doi.org/10.7554/eLife.06462.001 PMID:26026148

  6. Photothermally triggered actuation of hybrid materials as a new platform for in vitro cell manipulation

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

    Sutton, Amy; Shirman, Tanya; Timonen, Jaakko V. I.

    Mechanical forces in the cell’s natural environment have a crucial impact on growth, differentiation and behaviour. Few areas of biology can be understood without taking into account how both individual cells and cell networks sense and transduce physical stresses. However, the field is currently held back by the limitations of the available methods to apply physiologically relevant stress profiles on cells, particularly with sub-cellular resolution, in controlled in vitro experiments. Here we report a new type of active cell culture material that allows highly localized, directional and reversible deformation of the cell growth substrate, with control at scales ranging frommore » the entire surface to the subcellular, and response times on the order of seconds. These capabilities are not matched by any other method, and this versatile material has the potential to bridge the performance gap between the existing single cell micro-manipulation and 2D cell sheet mechanical stimulation techniques.« less

  7. BK Channels Are Required for Multisensory Plasticity in the Oculomotor System.

    PubMed

    Nelson, Alexandra B; Faulstich, Michael; Moghadam, Setareh; Onori, Kimberly; Meredith, Andrea; du Lac, Sascha

    2017-01-04

    Neural circuits are endowed with several forms of intrinsic and synaptic plasticity that could contribute to adaptive changes in behavior, but circuit complexities have hindered linking specific cellular mechanisms with their behavioral consequences. Eye movements generated by simple brainstem circuits provide a means for relating cellular plasticity to behavioral gain control. Here we show that firing rate potentiation, a form of intrinsic plasticity mediated by reductions in BK-type calcium-activated potassium currents in spontaneously firing neurons, is engaged during optokinetic reflex compensation for inner ear dysfunction. Vestibular loss triggers transient increases in postsynaptic excitability, occlusion of firing rate potentiation, and reductions in BK currents in vestibular nucleus neurons. Concurrently, adaptive increases in visually evoked eye movements rapidly restore oculomotor function in wild-type mice but are profoundly impaired in BK channel-null mice. Activity-dependent regulation of intrinsic excitability may be a general mechanism for adaptive control of behavioral output in multisensory circuits. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. A stochastic reaction-diffusion model for protein aggregation on DNA

    NASA Astrophysics Data System (ADS)

    Voulgarakis, Nikolaos K.

    Vital functions of DNA, such as transcription and packaging, depend on the proper clustering of proteins on the double strand. The present study investigates how the interplay between DNA allostery and electrostatic interactions affects protein clustering. The statistical analysis of a simple but transparent computational model reveals two major consequences of this interplay. First, depending on the protein and salt concentration, protein filaments exhibit a bimodal DNA stiffening and softening behavior. Second, within a certain domain of the control parameters, electrostatic interactions can cause energetic frustration that forces proteins to assemble in rigid spiral configurations. Such spiral filaments might trigger both positive and negative supercoiling, which can ultimately promote gene compaction and regulate the promoter. It has been experimentally shown that bacterial histone-like proteins assemble in similar spiral patterns and/or exhibit the same bimodal behavior. The proposed model can, thus, provide computational insights into the physical mechanisms used by proteins to control the mechanical properties of the DNA.

  9. Epigenetic regulation of serotype expression antagonizes transcriptome dynamics in Paramecium tetraurelia.

    PubMed

    Cheaib, Miriam; Dehghani Amirabad, Azim; Nordström, Karl J V; Schulz, Marcel H; Simon, Martin

    2015-08-01

    Phenotypic variation of a single genotype is achieved by alterations in gene expression patterns. Regulation of such alterations depends on their time scale, where short-time adaptations differ from permanently established gene expression patterns maintained by epigenetic mechanisms. In the ciliate Paramecium, serotypes were described for an epigenetically controlled gene expression pattern of an individual multigene family. Paradoxically, individual serotypes can be triggered in Paramecium by alternating environments but are then stabilized by epigenetic mechanisms, thus raising the question to which extend their expression follows environmental stimuli. To characterize environmental adaptation in the context of epigenetically controlled serotype expression, we used RNA-seq to characterize transcriptomes of serotype pure cultures. The resulting vegetative transcriptome resource is first analysed for genes involved in the adaptive response to the altered environment. Secondly, we identified groups of genes that do not follow the adaptive response but show co-regulation with the epigenetically controlled serotype system, suggesting that their gene expression pattern becomes manifested by similar mechanisms. In our experimental set-up, serotype expression and the entire group of co-regulated genes were stable among environmental changes and only heat-shock genes altered expression of these gene groups. The data suggest that the maintenance of these gene expression patterns in a lineage represents epigenetically controlled robustness counteracting short-time adaptation processes. © The Author 2015. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  10. An integrated mechanism of cardiomyocyte nuclear Ca(2+) signaling.

    PubMed

    Ibarra, Cristián; Vicencio, Jose Miguel; Varas-Godoy, Manuel; Jaimovich, Enrique; Rothermel, Beverly A; Uhlén, Per; Hill, Joseph A; Lavandero, Sergio

    2014-10-01

    In cardiomyocytes, Ca(2+) plays a central role in governing both contraction and signaling events that regulate gene expression. Current evidence indicates that discrimination between these two critical functions is achieved by segregating Ca(2+) within subcellular microdomains: transcription is regulated by Ca(2+) release within nuclear microdomains, and excitation-contraction coupling is regulated by cytosolic Ca(2+). Accordingly, a variety of agonists that control cardiomyocyte gene expression, such as endothelin-1, angiotensin-II or insulin-like growth factor-1, share the feature of triggering nuclear Ca(2+) signals. However, signaling pathways coupling surface receptor activation to nuclear Ca(2+) release, and the phenotypic responses to such signals, differ between agonists. According to earlier hypotheses, the selective control of nuclear Ca(2+) signals by activation of plasma membrane receptors relies on the strategic localization of inositol trisphosphate receptors at the nuclear envelope. There, they mediate Ca(2+) release from perinuclear Ca(2+) stores upon binding of inositol trisphosphate generated in the cytosol, which diffuses into the nucleus. More recently, identification of such receptors at nuclear membranes or perinuclear sarcolemmal invaginations has uncovered novel mechanisms whereby agonists control nuclear Ca(2+) release. In this review, we discuss mechanisms for the selective control of nuclear Ca(2+) signals with special focus on emerging models of agonist receptor activation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Attention biases visual activity in visual short-term memory.

    PubMed

    Kuo, Bo-Cheng; Stokes, Mark G; Murray, Alexandra M; Nobre, Anna Christina

    2014-07-01

    In the current study, we tested whether representations in visual STM (VSTM) can be biased via top-down attentional modulation of visual activity in retinotopically specific locations. We manipulated attention using retrospective cues presented during the retention interval of a VSTM task. Retrospective cues triggered activity in a large-scale network implicated in attentional control and led to retinotopically specific modulation of activity in early visual areas V1-V4. Importantly, shifts of attention during VSTM maintenance were associated with changes in functional connectivity between pFC and retinotopic regions within V4. Our findings provide new insights into top-down control mechanisms that modulate VSTM representations for flexible and goal-directed maintenance of the most relevant memoranda.

  12. System for Multiplexing Acoustic Emission (AE) Instrumentation

    NASA Technical Reports Server (NTRS)

    Prosser, William H. (Inventor); Perey, Daniel F. (Inventor); Gorman, Michael R. (Inventor); Scales, Edgar F. (Inventor)

    2003-01-01

    An acoustic monitoring device has at least two acoustic sensors with a triggering mechanism and a multiplexing circuit. After the occurrence of a triggering event at a sensor, the multiplexing circuit allows a recording component to record acoustic emissions at adjacent sensors. The acoustic monitoring device is attached to a solid medium to detect the occurrence of damage.

  13. Increased microtubule assembly rates mediate chromosomal instability in colorectal cancer cells

    PubMed Central

    Ertych, Norman; Stolz, Ailine; Stenzinger, Albrecht; Weichert, Wilko; Kaulfuß, Silke; Burfeind, Peter; Aigner, Achim; Wordeman, Linda

    2015-01-01

    Chromosomal instability (CIN) is defined as the perpetual missegregation of whole chromosomes during mitosis and represents a hallmark of human cancer. However, the mechanisms causing CIN and its consequences on tumor growth are largely unknown. We identify an increase in microtubule plus end assembly rates as a fundamental trigger for CIN in CRC cells. This trigger is mediated by overexpression of the oncogene AURKA or by loss of the tumor suppressor gene CHK2, a genetic constitution found in 73% of human colorectal cancers. Increased microtubule assembly rates are associated with transient abnormalities in mitotic spindle geometry promoting the generation of lagging chromosomes and resulting in CIN. Reconstitution of proper microtubule assembly rates by chemical or genetic means suppresses CIN and thereby, unexpectedly, accelerates tumor growth in vitro and in vivo. Thus, we identify a fundamental mechanism triggering CIN in cancer cells and reveal its adverse consequence on tumor growth. PMID:24976383

  14. AMPLITUDE DISCRIMINATOR HAVING SEPARATE TRIGGERING AND RECOVERY CONTROLS UTILIZING AUTOMATIC TRIGGERING

    DOEpatents

    Chase, R.L.

    1962-01-23

    A transistorized amplitude discriminator circuit is described in which the initial triggering sensitivity and the recovery threshold are separately adjustable in a convenient manner. The discriminator is provided with two independent bias components, one of which is for circuit hysteresis (recovery) and one of which is for trigger threshold level. A switching circuit is provided to remove the second bias component upon activation of the trigger so that the recovery threshold is always at the point where the trailing edge of the input signal pulse goes through zero or other desired value. (AEC)

  15. The Battle between Rotavirus and Its Host for Control of the Interferon Signaling Pathway

    PubMed Central

    Arnold, Michelle M.; Sen, Adrish; Greenberg, Harry B.; Patton, John T.

    2013-01-01

    Viral pathogens must overcome innate antiviral responses to replicate successfully in the host organism. Some of the mechanisms viruses use to interfere with antiviral responses in the infected cell include preventing detection of viral components, perturbing the function of transcription factors that initiate antiviral responses, and inhibiting downstream signal transduction. RNA viruses with small genomes and limited coding space often express multifunctional proteins that modulate several aspects of the normal host response to infection. One such virus, rotavirus, is an important pediatric pathogen that causes severe gastroenteritis, leading to ∼450,000 deaths globally each year. In this review, we discuss the nature of the innate antiviral responses triggered by rotavirus infection and the viral mechanisms for inhibiting these responses. PMID:23359266

  16. Smooth muscle cell phenotypic switching in stroke.

    PubMed

    Poittevin, Marine; Lozeron, Pierre; Hilal, Rose; Levy, Bernard I; Merkulova-Rainon, Tatiana; Kubis, Nathalie

    2014-06-01

    Disruption of cerebral blood flow after stroke induces cerebral tissue injury through multiple mechanisms that are not yet fully understood. Smooth muscle cells (SMCs) in blood vessel walls play a key role in cerebral blood flow control. Cerebral ischemia triggers these cells to switch to a phenotype that will be either detrimental or beneficial to brain repair. Moreover, SMC can be primarily affected genetically or by toxic metabolic molecules. After stroke, this pathological phenotype has an impact on the incidence, pattern, severity, and outcome of the cerebral ischemic disease. Although little research has been conducted on the pathological role and molecular mechanisms of SMC in cerebrovascular ischemic diseases, some therapeutic targets have already been identified and could be considered for further pharmacological development. We examine these different aspects in this review.

  17. Laser fusion pulse shape controller

    DOEpatents

    Siebert, Larry D.

    1977-01-01

    An apparatus for controlling the pulse shape, i.e., the pulse duration and intensity pattern, of a pulsed laser system, and which is particularly well adapted for controlling the pellet ignition pulse in a laser-driven fusion reaction system. The apparatus comprises a laser generator for providing an optical control pulse of the shape desired, a pulsed laser triggered by the control pulse, and a plurality of optical Kerr-effect gates serially disposed at the output of the pulsed laser and selectively triggered by the control pulse to pass only a portion of the pulsed laser output generally corresponding in shape to the control pulse.

  18. Frictional stability and earthquake triggering during fluid pressure stimulation of an experimental fault

    NASA Astrophysics Data System (ADS)

    Scuderi, M. M.; Collettini, C.; Marone, C.

    2017-11-01

    It is widely recognized that the significant increase of M > 3.0 earthquakes in Western Canada and the Central United States is related to underground fluid injection. Following injection, fluid overpressure lubricates the fault and reduces the effective normal stress that holds the fault in place, promoting slip. Although, this basic physical mechanism for earthquake triggering and fault slip is well understood, there are many open questions related to induced seismicity. Models of earthquake nucleation based on rate- and state-friction predict that fluid overpressure should stabilize fault slip rather than trigger earthquakes. To address this controversy, we conducted laboratory creep experiments to monitor fault slip evolution at constant shear stress while the effective normal stress was systematically reduced via increasing fluid pressure. We sheared layers of carbonate-bearing fault gouge in a double direct shear configuration within a true-triaxial pressure vessel. We show that fault slip evolution is controlled by the stress state acting on the fault and that fluid pressurization can trigger dynamic instability even in cases of rate strengthening friction, which should favor aseismic creep. During fluid pressurization, when shear and effective normal stresses reach the failure condition, accelerated creep occurs in association with fault dilation; further pressurization leads to an exponential acceleration with fault compaction and slip localization. Our work indicates that fault weakening induced by fluid pressurization can overcome rate strengthening friction resulting in fast acceleration and earthquake slip. Our work points to modifications of the standard model for earthquake nucleation to account for the effect of fluid overpressure and to accurately predict the seismic risk associated with fluid injection.

  19. Reactive oxygen species trigger Parkin/PINK1 pathway-dependent mitophagy by inducing mitochondrial recruitment of Parkin.

    PubMed

    Xiao, Bin; Goh, Jian-Yuan; Xiao, Lin; Xian, Hongxu; Lim, Kah-Leong; Liou, Yih-Cherng

    2017-10-06

    Defective mitophagy linked to dysfunction in the proteins Parkin and PTEN-induced putative kinase 1 (PINK1) is implicated in the pathogenesis of Parkinson's disease. Although the mechanism by which Parkin mediates mitophagy in a PINK1-dependent manner is becoming clearer, the triggers for this mitophagy pathway remain elusive. Reactive oxygen species (ROS) have been suggested as such triggers, but this proposal remains controversial because ROS scavengers fail to retard mitophagy. Here we demonstrate that the role of ROS in mitophagy has been underappreciated as a result of the inefficiency of ROS scavengers to control ROS bursts after high-dose treatment with carbonyl cyanide m -chlorophenylhydrazone. Supporting this, combinatorial treatment with N -acetyl-l-cysteine and catalase substantially inhibited the ROS upsurge and PINK1-dependent Parkin translocation to mitochondria in response to carbonyl cyanide m -chlorophenylhydrazone treatment. In addition to the chemical mitophagy inducer, overexpression of voltage-dependent anion channel 1 (VDAC1) induced Parkin translocation to mitochondria, presumably by stimulating ROS generation. Similarly, combined N -acetyl-l-cysteine and catalase treatment also suppressed VDAC1-induced redistribution of Parkin. Alongside these observations, we also found that the elevated protein level of PINK1 was not necessary for Parkin translocation to mitochondria. Thus, our data suggest that ROS may act as a trigger for the induction of Parkin/PINK1-dependent mitophagy. In addition, our study casts doubt on the importance of protein quantity of PINK1 in the recruitment of Parkin to mitochondria. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Controlling a stream of paranoia evoking events in a virtual reality environment.

    PubMed

    Isnanda, Reza Giga; Brinkman, Willem-Paul; Veling, Wim; van der Gaag, Mark; Neerincx, Mark

    2014-01-01

    Although virtual reality exposure has been reported as a method to induce paranoid thought, little is known about mechanisms to control specific virtual stressors. This paper reports on a study that examines the effect of controlling the stream of potential paranoia evoking events in a virtual restaurant world. A 2-by-2 experiment with a non-clinical group (n = 24) was conducted with as two within-subject factors: (1) the cycle time (short/long) for when the computer considers activation of a paranoia evoking event and (2) the probability that a paranoia-evoking event (low/high) would be triggered at the completion of a cycle. The results showed a significant main effect for the probability factor and two-way interaction effect with the cycle time factor on the number of paranoid comments participants made and their self-reported anxiety.

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